Teelthandleiding korrelmais en Corn Cob Mix (CCM) - voedingsaspecten

NARCIS (Netherlands)

Brink, van den L.; Groten, J.A.M.

2005-01-01

Korrelmaïs wordt overwegend verwerkt in mengvoer voor pluimvee en varkens. CCM wordt hoofdzakelijk vervoederd aan varkens, maar daarnaast ook aan rundvee. MKS is voornamelijk bestemd voor rundvee en paarden

Novel functions of CCM1 delimit the relationship of PTB/PH domains.

Science.gov (United States)

Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

2017-10-01

Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

Laboratory evaluation of a new strain CCM 8367 of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) on Spodoptera littoralis (Boisd.)

Czech Academy of Sciences Publication Activity Database

Hussein, Hany; Zemek, Rostislav; Habuštová, Oxana; Prenerová, Eva; Adel, M. M.

2013-01-01

Roč. 46, č. 11 (2013), s. 1307-1319 ISSN 0323-5408 R&D Projects: GA MŠk 2B06005 Institutional support: RVO:60077344 Keywords : entomopathogenic fungi * Isaria fumosorosea * CCM 8367 Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection

Flyback CCM inverter for AC module applications: iterative learning control and convergence analysis

Science.gov (United States)

Lee, Sung-Ho; Kim, Minsung

2017-12-01

This paper presents an iterative learning controller (ILC) for an interleaved flyback inverter operating in continuous conduction mode (CCM). The flyback CCM inverter features small output ripple current, high efficiency, and low cost, and hence it is well suited for photovoltaic power applications. However, it exhibits the non-minimum phase behaviour, because its transfer function from control duty to output current has the right-half-plane (RHP) zero. Moreover, the flyback CCM inverter suffers from the time-varying grid voltage disturbance. Thus, conventional control scheme results in inaccurate output tracking. To overcome these problems, the ILC is first developed and applied to the flyback inverter operating in CCM. The ILC makes use of both predictive and current learning terms which help the system output to converge to the reference trajectory. We take into account the nonlinear averaged model and use it to construct the proposed controller. It is proven that the system output globally converges to the reference trajectory in the absence of state disturbances, output noises, or initial state errors. Numerical simulations are performed to validate the proposed control scheme, and experiments using 400-W AC module prototype are carried out to demonstrate its practical feasibility.

CCM proteins control endothelial β1 integrin dependent response to shear stress

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Zuzana Macek Jilkova

2014-11-01

Full Text Available Hemodynamic shear stress from blood flow on the endothelium critically regulates vascular function in many physiological and pathological situations. Endothelial cells adapt to shear stress by remodeling their cytoskeletal components and subsequently by changing their shape and orientation. We demonstrate that β1 integrin activation is critically controlled during the mechanoresponse of endothelial cells to shear stress. Indeed, we show that overexpression of the CCM complex, an inhibitor of β1 integrin activation, blocks endothelial actin rearrangement and cell reorientation in response to shear stress similarly to β1 integrin silencing. Conversely, depletion of CCM2 protein leads to an elongated “shear-stress-like” phenotype even in the absence of flow. Taken together, our findings reveal the existence of a balance between positive extracellular and negative intracellular signals, i.e. shear stress and CCM complex, for the control of β1 integrin activation and subsequent adaptation of vascular endothelial cells to mechanostimulation by fluid shear stress.

Evaluation of stability of interface between CCM (Co-Cr-Mo) UCLA abutment and external hex implant.

Science.gov (United States)

Yoon, Ki-Joon; Park, Young-Bum; Choi, Hyunmin; Cho, Youngsung; Lee, Jae-Hoon; Lee, Keun-Woo

2016-12-01

The purpose of this study is to evaluate the stability of interface between Co-Cr-Mo (CCM) UCLA abutment and external hex implant. Sixteen external hex implant fixtures were assigned to two groups (CCM and Gold group) and were embedded in molds using clear acrylic resin. Screw-retained prostheses were constructed using CCM UCLA abutment and Gold UCLA abutment. The external implant fixture and screw-retained prostheses were connected using abutment screws. After the abutments were tightened to 30 Ncm torque, 5 kg thermocyclic functional loading was applied by chewing simulator. A target of 1.0 × 10 6 cycles was applied. After cyclic loading, removal torque values were recorded using a driving torque tester, and the interface between implant fixture and abutment was evaluated by scanning electronic microscope (SEM). The means and standard deviations (SD) between the CCM and Gold groups were analyzed with independent t-test at the significance level of 0.05. Fractures of crowns, abutments, abutment screws, and fixtures and loosening of abutment screws were not observed after thermocyclic loading. There were no statistically significant differences at the recorded removal torque values between CCM and Gold groups ( P >.05). SEM analysis revealed that remarkable wear patterns were observed at the abutment interface only for Gold UCLA abutments. Those patterns were not observed for other specimens. Within the limit of this study, CCM UCLA abutment has no statistically significant difference in the stability of interface with external hex implant, compared with Gold UCLA abutment.

Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence.

Science.gov (United States)

Bosch-Capblanch, Xavier; Marceau, Claudine

2014-12-01

included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations.

Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence

Science.gov (United States)

Bosch–Capblanch, Xavier; Marceau, Claudine

2014-01-01

components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations. PMID:25520793

Potential of Lactobacillus plantarum ccm 3627 and Lactobacillus brevis ccm 1815 for fermentation of cereal substrates

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Kvetoslava Romanová

2017-01-01

Full Text Available Lactobacillus is the most representative strain in a group of lactic acid bacteria, which perform an essential role in the preservation and production of wholesome foods. Lactic acid fermentation is the oldest traditional method for preparation of fermented vegetables, meat products, dairy products and cereal foods. Cereal grains are considered to be one of the most important sources of dietary proteins, carbohydrates, vitamins, minerals and fibre for people. The main exploitation of cereals is to prepare sourdough, which is a mixture of wheat, rye or other cereal flour with water and contains yeasts and lactobacilli. The basic biochemical changes that occur in sourdough bread fermentation are acidification of the dough with organic acids produced by the lactobacilli and leavening with carbon dioxide produced by the yeast and the lactobacilli. Acidification perhaps initiate enzymatic processes of proteins and phytates degradation. Lactobacilli produce various enzymes which make flavour precursors, improve of mineral bioavailability or degrade celiac active peptides, because some species of lactobacilli produce specific peptidases during growth, which are capable to hydrolyze hardly cleavable, celiac-active proline-rich peptides. Microbial fermentation with selected strains of lactobacilli may be new alternative approach for modification of gluten by hydrolysis. In this paper are described growth characteristics and intracellular aminopeptidases activities of Lactobacillus plantarum CCM 3627 and Lactobacillus brevis CCM 1815. Work was focused on characterization of the lactobacilli for potential usage as a starter culture in further fermentation experiments.

Teelthandleiding korrelmais en Corn Cob Mix (CCM) - bemesting

NARCIS (Netherlands)

Brink, van den L.; Groten, J.A.M.

2005-01-01

De bemesting van korrelmaïs, CCM en MKS komt grotendeels overeen met die van snijmaïs. Voor de bemestingsadviezen wordt dan ook verwezen naar http://www.handboeksnijmais.nl/. Er zijn echter voor de situatie van twee of meer jaren achter elkaar telen van het gewas wel enkele aanpassingen nodig. Dit

STAR-CCM+ (CFD) Calculations and Validation L3:VVI.H2L.P15.02

Energy Technology Data Exchange (ETDEWEB)

Gilkey, Lindsay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-09-05

This milestone presents a demonstration of the High-to-Low (Hi2Lo) process in the VVI focus area. Validation and additional calculations with the commercial computational fluid dynamics code, STAR-CCM+, were performed using a 5x5 fuel assembly with non-mixing geometry and spacer grids. This geometry was based on the benchmark experiment provided by Westinghouse. Results from the simulations were compared to existing experimental data and to the subchannel thermal-hydraulics code COBRA-TF (CTF). An uncertainty quantification (UQ) process was developed for the STAR-CCM+ model and results of the STAR UQ were communicated to CTF. Results from STAR-CCM+ simulations were used as experimental design points in CTF to calibrate the mixing parameter β and compared to results obtained using experimental data points. This demonstrated that CTF’s β parameter can be calibrated to match existing experimental data more closely. The Hi2Lo process for the STAR-CCM+/CTF code coupling was documented in this milestone and closely linked L3:VVI.H2LP15.01 milestone report.

Identification of a novel gene cluster in the upstream region of the S-layer gene sbpA involved in cell wall metabolism of Lysinibacillus sphaericus CCM 2177 and characterization of the recombinantly produced autolysin and pyruvyl transferase.

Science.gov (United States)

Pleschberger, Magdalena; Hildner, Florian; Rünzler, Dominik; Gelbmann, Nicola; Mayer, Harald F; Sleytr, Uwe B; Egelseer, Eva M

2013-05-01

The S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177 assembles into a square (p4) lattice structure and recognizes a pyruvylated secondary cell wall polymer (SCWP) as the proper anchoring structure to the rigid cell wall layer. Sequencing of 8,004 bp in the 5'-upstream region of the S-layer gene sbpA led to five ORFs-encoding proteins involved in cell wall metabolism. After cloning and heterologous expression of ORF1 and ORF5 in Escherichia coli, the recombinant autolysin rAbpA and the recombinant pyruvyl transferase rCsaB were isolated, purified, and correct folding was confirmed by circular dichroism. Although rAbpA encoded by ORF1 showed amidase activity, it could attack whole cells of Ly. sphaericus CCM 2177 only after complete extraction of the S-layer lattice. Despite the presence of three S-layer-homology motifs on the N-terminal part, rAbpA did not show detectable affinity to peptidoglycan-containing sacculi, nor to isolated SCWP. As the molecular mass of the autolysin lies above the molecular exclusion limit of the S-layer, AbpA is obviously trapped within the rigid cell wall layer by the isoporous protein lattice. Immunogold-labeling of ultrathin-sectioned whole cells of Ly. sphaericus CCM 2177 with a polyclonal rabbit antiserum raised against rCsaB encoded by ORF5, and cell fractionation experiments demonstrated that the pyruvyl transferase was located in the cytoplasm, but not associated with cell envelope components including the plasma membrane. In enzymatic assays, rCsaB clearly showed pyruvyl transferase activity. By using RT-PCR, specific transcripts for each ORF could be detected. Cotranscription could be confirmed for ORF2 and ORF3.

Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

Directory of Open Access Journals (Sweden)

Watson Andrew J

2007-01-01

Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.

Relaunch of the official community health worker programme in Mozambique: is there a sustainable basis for iCCM policy?

Science.gov (United States)

Chilundo, Baltazar Gm; Cliff, Julie L; Mariano, Alda Re; Rodríguez, Daniela C; George, Asha

2015-12-01

In Mozambique, integrated community case management (iCCM) of diarrhoea, malaria and pneumonia is embedded in the national community health worker (CHW) programme, mainstreaming it into government policy and service delivery. Since its inception in 1978, the CHW programme has functioned unevenly, was suspended in 1989, but relaunched in 2010. To assess the long-term success of iCCM in Mozambique, this article addresses whether the current CHW programme exhibits characteristics that facilitate or impede its sustainability. We undertook a qualitative case study based on document review (n = 54) and key informant interviews (n = 21) with respondents from the Ministry of Health (MOH), multilateral and bilateral agencies and non-governmental organizations (NGOs) in Maputo in 2012. Interviews were mostly undertaken in Portuguese and all were coded using NVivo. A sustainability framework guided thematic analysis according to nine domains: strategic planning, organizational capacity, programme adaptation, programme monitoring and evaluation, communications, funding stability, political support, partnerships and public health impact. Government commitment was high, with the MOH leading a consultative process in Maputo and facilitating successful technical coordination. The MOH made strategic decisions to pay CHWs, authorize their prescribing abilities, foster guidance development, support operational planning and incorporate previously excluded 'old' CHWs. Nonetheless, policy negotiations excluded certain key actors and uncertainty remains about CHW integration into the civil service and their long-term retention. In addition, reliance on NGOs and donor funding has led to geographic distortions in scaling up, alongside challenges in harmonization. Finally, dependence on external funding, when both external and government funding are declining, may hamper sustainability. Our analysis represents a nuanced assessment of the various domains that influence CHW programme

Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

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Nengyi Zhang

2010-04-01

Full Text Available Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system.We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication.Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

Estimate of Leaf Chlorophyll and Nitrogen Content in Asian Pear (Pyrus serotina Rehd. by CCM-200

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Mostafa GHASEMI

2011-03-01

Full Text Available In many cases evaluation of chlorophyll and nitrogen content in plants need to destructive methods, more time and organic solvents. Application of chlorophyll meters save time and resources. The aim of this study was estimating of chlorophyll and nitrogen content in Asian pear leaves using non-destructive method and rapid quantification of chlorophyll by chlorophyll content meter (CCM-200. This study was conducted on 8 years old Asian pear trees during June 2008 in Tehran, Iran. To develop our regression model, the chlorophyll meter data were correlated with extracted chlorophyll and nitrogen content data obtained from DMSO and Kejeldal methods, respectively. The results showed that, there was positive and linear correlation between CCM-200 data and chlorophyll a (R�=0.7183, chlorophyll b (R�=0.8523, total chlorophyll (R�=0.90, and total nitrogen content (R�=0.76 in Asian pear leaves. Thus, it can be concluded that, CCM-200 can be used in order to predict both chlorophyll and nitrogen content in Asian pear leaves.

Sulfosys (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation.

NARCIS (Netherlands)

Albers, S.V.; Birkeland, N.K.; Driessen, A.J.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.J.; Siebers, B.; Sierocinski, P.; Steuer, R.; van der Oost, J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

2009-01-01

SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

SulfoSYS (Sulfolobus Systems Biology) : towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

NARCIS (Netherlands)

Albers, Sonja-Verena; Birkeland, Nils-Kare; Driessen, Arnold J. M.; Gertig, Susanne; Haferkamp, Patrick; Klenk, Hans-Peter; Kouril, Theresa; Manica, Andrea; Pham, Trong K.; Ruoff, Peter; Schleper, Christa; Schomburg, Dietmar; Sharkey, Kieran J.; Siebers, Bettina; Sierocinski, Pawel; Steuer, Ralf; van der Oost, John; Westerhoff, Hans V.; Wieloch, Patricia; Wright, Phillip C.; Zaparty, Melanie; Birkeland, Nils-Kåre

SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. in Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

SulfoSYS (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

NARCIS (Netherlands)

Albers, S.V.; Birkeland, N.K.; Driessen, A.J.M.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.; Siebers, B.; Sierocinski, P.; Steur, R.; Oost, van der J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

2009-01-01

SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

Demand generation and social mobilisation for integrated community case management (iCCM) and child health: Lessons learned from successful programmes in Niger and Mozambique.

Science.gov (United States)

Sharkey, Alyssa B; Martin, Sandrine; Cerveau, Teresa; Wetzler, Erica; Berzal, Rocio

2014-12-01

We present the approaches used in and outcomes resulting from integrated community case management (iCCM) programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care-seeking within 24 hours and care-seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers' ability to assess and treat illnesses can lead to improved care-seeking and utilisation, and community ownership for iCCM.

Demand generation and social mobilisation for integrated community case management (iCCM and child health: Lessons learned from successful programmes in Niger and Mozambique

Directory of Open Access Journals (Sweden)

Alyssa B Sharkey

2014-11-01

Full Text Available We present the approaches used in and outcomes resulting from integrated community case management (iCCM programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care–seeking within 24 hours and care–seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers’ ability to assess and treat illnesses can lead to improved care–seeking and utilisation, and community ownership for iCCM.

A comparison of ANSYS Fluent and STAR-CCM+ simulations for a tangent ogive slender body with a structured mesh at incompressible flow conditions

CSIR Research Space (South Africa)

Schoombie, Janine

2017-10-01

Full Text Available -CCM+ (1) • Why STAR-CCM+? – In 2017 only a STAR-CCM+ v11.06 commercial licence was available – Didn’t want to start from scratch – Test solver with identical mesh STEP 1: • Import Fluent .cas files - Imported as a volume mesh - No mesh continuum... stream_source_info Schoombie_19954_2017.pdf.txt stream_content_type text/plain stream_size 3069 Content-Encoding UTF-8 stream_name Schoombie_19954_2017.pdf.txt Content-Type text/plain; charset=UTF-8 A comparison of ANSYS...

A Unified Voltage Harmonic Control Strategy for Coordinated Compensation with VCM and CCM Converters

DEFF Research Database (Denmark)

Zhao, Xin; Meng, Lexuan; Xie, Chuan

2018-01-01

-controlled mode (VCM) and current-controlled mode (CCM), need to cooperatively provide the compensation function. Aiming at this objective, this paper proposes a unified voltage harmonic mitigation strategy for VCM and CCM converters with high harmonic current sharing accuracy. Another advantage of the proposal......Harmonics have been considered as one of the major issues in modern power grids. Considering the high penetration level of power electronic converter interfaced distributed generators (DGs), it is of interest to provide ancillary services through DG interfacing converters, such as harmonic...... compensation. In case of that, multiple DG interfacing converters are utilized to compensate harmonics, and the compensation effort should be properly shared among these converters. However, it is rarely considered in existing literatures that converters operating in different modes, such as voltage...

Setting global research priorities for integrated community case management (iCCM: Results from a CHNRI (Child Health and Nutrition Research Initiative exercise

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Kerri Wazny

2014-11-01

Full Text Available Aims: to systematically identify global research gaps and resource priorities for integrated community case management (iCCM. Methods: an iCCM Child Health and Nutrition Research Initiative (CHNRI Advisory Group, in collaboration with the Community Case Management Operational Research Group (CCM ORG identified experts to participate in a CHNRI research priority setting exercise. These experts generated and systematically ranked research questions for iCCM. Research questions were ranked using a “Research Priority Score” (RPS and the “Average Expert Agreement” (AEA was calculated for every question. Our groups of experts were comprised of both individuals working in Ministries of Health or Non Governmental Organizations (NGOs in low– and middle–income countries (LMICs and individuals working in high–income countries (HICs in academia or NGO headquarters. A Spearman's Rho was calculated to determine the correlation between the two groups' research questions' ranks. Results: The overall RPS ranged from 64.58 to 89.31, with a median score of 81.43. AEA scores ranged from 0.54 to 0.86. Research questions involving increasing the uptake of iCCM services, research questions concerning the motivation, retention, training and supervision of Community Health Workers (CHWs and concerning adding additional responsibilities including counselling for infant and young child feeding (IYCF and treatment of severe acute malnutrition (SAM ranked highly. There was weak to moderate, statistically significant, correlation between scores by representatives of high–income countries and those working in–country or regionally (Spearman's ρ = 0.35034, P < 0.01. Conclusions: Operational research to determine optimal training, supervision and modes of motivation and retention for the CHW is vital for improving iCCM, globally, as is research to motivate caregivers to take advantage of iCCM services. Experts working in–country or regionally in

Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

Science.gov (United States)

Lorefice, S.; Becerra, L. O.

2017-01-01

Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Chemical cleavage reactions of DNA on solid support: application in mutation detection

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Cotton Richard GH

2003-05-01

Full Text Available Abstract Background The conventional solution-phase Chemical Cleavage of Mismatch (CCM method is time-consuming, as the protocol requires purification of DNA after each reaction step. This paper describes a new version of CCM to overcome this problem by immobilizing DNA on silica solid supports. Results DNA test samples were loaded on to silica beads and the DNA bound to the solid supports underwent chemical modification reactions with KMnO4 (potassium permanganate and hydroxylamine in 3M TEAC (tetraethylammonium chloride solution. The resulting modified DNA was then simultaneously cleaved by piperidine and removed from the solid supports to afford DNA fragments without the requirement of DNA purification between reaction steps. Conclusions The new solid-phase version of CCM is a fast, cost-effective and sensitive method for detection of mismatches and mutations.

Biodistribution of 99mTc labelled anti TAG 72 chimeric McAb ccM4 in nude mice and preliminary clinical study

International Nuclear Information System (INIS)

Ma Qingjie; Zhao Jie; Zhang Yingnan; Gao Fengtong; Liu Shuqing

1995-01-01

Chimeric McAb ccM 4 was labelled with 99m Tc by direct method. The antibody was reduced by molar excess 2-mercaptoethanol (2-ME; Ab, 1000:1). The reduced ccM 4 chimeric McAb was mixed with 99m Tc reduced by SnCl 2 and 99m Tc labelling efficiency was 98%. The immunoreactivity did not change after labelling. The biodistribution of 99m Tc-ccM 4 was performed in nude mice and patients with stomach carcinoma. There was significantly more radioactivity in tumor than in the rest of the body in nude mice. Radioimmunoimaging of ccM 4 in 10 patients of gastric cancer was also presented

Verteerbaarheid en voederwaarde van diverse kwaliteiten graskuil en van CCM bij biologische zeugen = Digestibility and nutritive value of several qualities of grass silage and of CCM in organic housed gestating sows

NARCIS (Netherlands)

Peet-Schwering, van der C.M.C.; Binnendijk, G.P.; Diepen, van J.T.M.

2010-01-01

The chemical composition, digestibility and energy value of five qualities of grass silage and of CCM (Corn cob mix) were investigated in organic housed gestating sows. The dry matter content of the five grass silages varied between 21.3 and 24.9%. The energy value per kg dry matter varied between

Structure/Function of the Novel Proteins LCIB and LCIC in the Chlamydomonas CCM

Energy Technology Data Exchange (ETDEWEB)

Martin, Spalding H. [Iowa State Univ., Ames, IA (United States). Dept. of Genetics, Development and Cell Biology

2017-05-09

The goal of this project was to investigate the function of two novel proteins, LCIB and LCIC, which together form an essential protein complex that is required for function of a carbon-dioxide-concentrating mechanism (CCM) required by microalgae to grow in environments where carbon dioxide levels are at or below air equilibration levels.

Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats

Directory of Open Access Journals (Sweden)

Ramesh Bellamkonda

2018-01-01

Full Text Available The present study was proposed to elucidate the effect of Commiphora mukul gum resin elthanolic extract treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided into four groups: two of these groups (group C and C+CM were fed with standard pellet diet and the other two groups (group F and F+CM were fed with high fructose (66 % diet. C. mukul suspension in 5% Tween-80 in distilled water (200 mg/kg body weight/day was administered orally to group C+CM and group F+CM. At the end of 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F decreased significantly with C. mukul treatment in group F+CM. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. mukul treatment in group F+CM. In conclusion, our study demonstrated that C. mukul treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose induced alterations in carbohydrate and lipid metabolisms by the extract which was further supported by histopathological results from liver samples which showed regeneration of the hepatocytes. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

Improving effectiveness in e-marketing communication for Chinese SMEs: 2CCM

OpenAIRE

Zhao, Ying

2014-01-01

The purpose of this thesis was to come up with perspectives on improving effective-ness in e-marketing communication for Chinese SMEs. The aim of this thesis was to analyze Chinese e-marketing communication channels and message delivery. This thesis was done for 2CCM, which is an online store for selling fashionable and stylish high-end products. The thesis was roughly divided into two parts which were theoretical part and rec-ommendations. The theoretical part introduced the concept, Ch...

On the cradle of CCM research: discovery, development, and challenges ahead.

Science.gov (United States)

Kaplan, Aaron

2017-06-01

Herein, 40 years after its discovery, I briefly and critically survey the development of ideas that propelled research on CO2-concentrating mechanisms (CCMs; a term proposed by Dean Price) of phytoplankton, mainly focusing on cyanobacteria. This is not a comprehensive review on CCM research, but a personal view on the past developments and challenges that lie ahead. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Investigating the thermal hydraulic performance of spacer grid with mixing vanes using STAR-CCM+ and MATRA

International Nuclear Information System (INIS)

Agbodemegbe, V. Y.

2014-07-01

Enhancement of heat transfer for flow through rod bundles is linked to the extent and sustainability of mixing in the flow geometry. Spacer grids used as support for rod bundles in nuclear reactors, when attached with ditferent designs of mixing vanes promote turbulent mixing by inducing swirl or forced lateral convection that improves mixing within or between sub-channels. The improved turbulent mixing raises the margin of the onset of critical heat flux in light water reactors (LWR) and also ensures a higher fuel cycle economy. To optimize design of mixing vanes and performance of spacer grids with mixing vanes, computational fluid dynamic simulations arc carried out on new designs and validated experimentally prior to industrial application. In the present study, computational fluid dynamic simulation using STAR-CCM+ and sub-channel analysis with MATRA were performed for flow of water through a 5 X 5 rod bundle geometry for which the rod to rod pitch to diameter ratio was 1.33 and the wall to rod pitch to diameter ratio was 0.74. The two layer k-epsilon turbulence model with an all- y + automatic wall treatment function in STAR-CCM+ were adopted for an isothermal single phase flow through the geometry with imposed cyclic periodic and non-cyclic periodic interface boundary conditions. The objective was to primarily investigate the detail flow behavior in rod bundle in the presence of spacer grids with and without attached mixing vanes. Furthermore, the present study also investigated the extent of turbulent mixing and lateral mass flux induced by the mixing vanes through comparative analysis of parametric trends for spacer grid with and without mixing vanes. New models and empirical correlations for describing the mixing vanes effects were also developed. These semi-empirical correlations improved the prediction for lateral mass flux due to turbulence, fraction of flow diverted through gaps and cross-flow resistance coefficients. Validation of simulation results

Nuclear reactor multi-physics simulations with coupled MCNP5 and STAR-CCM+

International Nuclear Information System (INIS)

Cardoni, Jeffrey Neil; Rizwan-uddin

2011-01-01

The MCNP5 Monte Carlo particle transport code has been coupled to the computational fluid dynamics code, STAR-CCM+, to provide a high fidelity multi-physics simulation tool for pressurized water nuclear reactors. The codes are executed separately and coupled externally through a Perl script. The Perl script automates the exchange of temperature, density, and volumetric heating information between the codes using ASCII text data files. Fortran90 and Java utility programs assist job automation with data post-processing and file management. The MCNP5 utility code, MAKXSF, pre-generates temperature dependent cross section libraries for the thermal feedback calculations. The MCNP5–STAR-CCM+ coupled simulation tool, dubbed MULTINUKE, was applied to a steady state, PWR cell model to demonstrate its usage and capabilities. The demonstration calculation showed reasonable results that agree with PWR values typically reported in literature. Temperature and fission reaction rate distributions were realistic and intuitive. Reactivity coefficients were also deemed reasonable in comparison to historically reported data. The demonstration problem consisted of 9,984 CFD cells and 7,489 neutronic cells. MCNP5 tallied fission energy deposition over 3,328 UO_2 cells. The coupled solution converged within eight hours and in three MULTINUKE iterations. The simulation was carried out on a 64 bit, quad core, Intel 2.8 GHz microprocessor with 1 GB RAM. The simulations on a quad core machine indicated that a massively parallelized implementation of MULTINUKE can be used to assess larger multi-million cell models. (author)

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

International Nuclear Information System (INIS)

Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta; Schuetz, Matthias; Karanikas, Georgios; Khazen, Cesar; Wolzt, Michael

2012-01-01

Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO 2 ) in patients with chronic heart failure using 11 C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. 11 C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO 2 and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min -1 g -1 with the device off and 0.80 ± 0.15 ml min -1 g -1 with the device on (p = 0.818), MVO 2 was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m 2 with the device off and 5.21 ± 1.36 mmHg ml/m 2 with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO 2 and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO 2 , even under stress conditions. (orig.)

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

Energy Technology Data Exchange (ETDEWEB)

Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Schuetz, Matthias; Karanikas, Georgios [Vienna General Hospital/Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Khazen, Cesar [Vienna General Hospital/ Medical University of Vienna, Department of Cardiothoracic Surgery, Vienna (Austria); Wolzt, Michael [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Vienna General Hospital/ Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria)

2012-03-15

Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO{sub 2}) in patients with chronic heart failure using {sup 11}C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. {sup 11}C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO{sub 2} and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 {+-} 0.18 ml min{sup -1} g{sup -1} with the device off and 0.80 {+-} 0.15 ml min{sup -1} g{sup -1} with the device on (p = 0.818), MVO{sub 2} was 6.81 {+-} 1.69 ml/min/100 g with the device off and 7.15 {+-} 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 {+-} 1.14 mmHg ml/m{sup 2} with the device off and 5.21 {+-} 1.36 mmHg ml/m{sup 2} with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO{sub 2} and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO{sub 2}, even under stress conditions. (orig.)

Gas Furnace with Pulsed Feeding of the Heating Agent for Volume Precision Heat Treatment of CCM Rolls

Science.gov (United States)

Moroz, V. I.; Egorova, V. M.; Gusev, S. V.

2001-05-01

A standard chamber batch furnace of the Severstal' plant has been modified for precision heat treatment of CCM rolls. The certification tests of a charge of rolls from steel 24KhM1F have shown the technical and economical advantages of the new design.

Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

Directory of Open Access Journals (Sweden)

Đurović Dušanka

2009-01-01

Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle

Science.gov (United States)

Hussein, Hany M.; Skoková Habuštová, Oxana; Půža, Vladimír; Zemek, Rostislav

2016-01-01

The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50) was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days) compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days). The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days); later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended. PMID:27015633

A new version of the CNRM Chemistry-Climate Model, CNRM-CCM: description and improvements from the CCMVal-2 simulations

Directory of Open Access Journals (Sweden)

M. Michou

2011-10-01

Full Text Available This paper presents a new version of the Météo-France CNRM Chemistry-Climate Model, so-called CNRM-CCM. It includes some fundamental changes from the previous version (CNRM-ACM which was extensively evaluated in the context of the CCMVal-2 validation activity. The most notable changes concern the radiative code of the GCM, and the inclusion of the detailed stratospheric chemistry of our Chemistry-Transport model MOCAGE on-line within the GCM. A 47-yr transient simulation (1960–2006 is the basis of our analysis. CNRM-CCM generates satisfactory dynamical and chemical fields in the stratosphere. Several shortcomings of CNRM-ACM simulations for CCMVal-2 that resulted from an erroneous representation of the impact of volcanic aerosols as well as from transport deficiencies have been eliminated.

Remaining problems concern the upper stratosphere (5 to 1 hPa where temperatures are too high, and where there are biases in the NO₂, N₂O₅ and O₃ mixing ratios. In contrast, temperatures at the tropical tropopause are too cold. These issues are addressed through the implementation of a more accurate radiation scheme at short wavelengths. Despite these problems we show that this new CNRM CCM is a useful tool to study chemistry-climate applications.

FOREWORD: The 4th CCM International Conference on Pressure Metrology from Ultra-High Vacuum to Very High Pressures (10-9 Pa to 109 Pa)

Science.gov (United States)

Legras, Jean-Claude; Jousten, Karl; Severn, Ian

2005-12-01

, particularly Gianfranco Molinar who offered much advice based on experience of organizing the previous conference. Special thanks must also be made to Mitsuru Tanaka, President of the CCM, and Andrew Wallard, Director of the BIPM, for their support of the event. The event was coordinated by Jasmina Bolfek-Radovani, of the Institute of Physics, without whose tireless efforts the event would not have been as successful. The production of this issue of Metrologia would not have been possible without the help and support of its editor, Jeffrey Williams. The National Measurement System Directorate of the Department of Trade and Industry supported the conference and it was sponsored by DH Instruments and BOC Edwards. Additional financial assistance was also received from Chell Instruments Ltd, DH-Budenberg, GE Infrastructure Sensing, Hi-Pro Pressure Products Ltd, Kurt J Lesker Company Ltd and Leybold Vacuum UK Ltd. Finally we would like to thank all of the conference participants who made the event both technically stimulating and enjoyable. By the time the next CCM Pressure conference is held in Berlin in 2011, pressure science and technology will undoubtedly have moved on still further and we may see the culmination of work to realize primary pressure standards by more fundamental methods.

Optimization of analysis best-estimate of a fuel element BWR with Code STAR-CCM+; Optimizacion del analisis best-estimate de un elemento combustible BWR con el codigo STAR-CCM+

Energy Technology Data Exchange (ETDEWEB)

Morgado Canada, E.; Concejal Barmejo, A.; Jimenez Varas, G.; Solar Martinez, A.

2014-07-01

The objective of the project is the evaluation of the code STAR-CCM +, as well as the establishment of guidelines and standardized procedures for the discretization of the area of study and the selection of physical models suitable for the simulation of BWR fuel. For this purpose several of BFBT experiments have simulated [1] provide a data base for the development of experiments for measuring distribution of fractions of holes to changes in power in order to find the most appropriate models for the simulation of the problem. (Author)

Impact of Amazon deforestation on climate simulations using the NCAR CCM2/BATS model

Energy Technology Data Exchange (ETDEWEB)

Hahmann, A.N.; Dickinson, R.E. [Univ. of Arizona, Tucson, AZ (United States)

1996-12-31

Model validation and results are briefly presented for a simulation of deforestation of the Amazon rainforest. This initial study is made using assumptions regarding deforestation similar to those in earlier studies with several versions of the NCAR Community Climate Model (CCM) couples to the Biosphere-Atmosphere Transfer Scheme (BATS). The model used is a revised version of the NCAR CCM Version 2 coupled to BATS Version 1e. This paper discusses the portion of validation dealing with the distribution of precipitation; the simulation displays very good agreement with observed rainfall rates for the austral summer. Preliminary results from an 8-year simulation of deforestation are similar to that of previous studies. Annual precipitation and evaporation are reduced, while surface air temperatures show a slight increase. A substantial bimodal pattern appears in the results, with the Amazon decrease of precipitation and temperature increase accompanied by changes in the opposite sign to the southeast of the Amazon. Similar patterns have occurred in other studies, but not always in exactly the same locations. Evidently, how much of the region of rainfall increase occurs in the deforested area over the Amazon strongly affects the inferred statistics. It is likely that this pattern depends on the model control climatology and possibly other features. 16 refs., 2 figs., 2 tabs.

The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

Science.gov (United States)

Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

2016-05-01

Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle.

Directory of Open Access Journals (Sweden)

Hany M Hussein

Full Text Available The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50 was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days. The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days; later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended.

A decision-support system for sustainable urban metabolism in Europe

Energy Technology Data Exchange (ETDEWEB)

Gonzalez, Ainhoa, E-mail: ainhoag@yahoo.com [Trinity Centre for Biodiversity Research, School of Natural Sciences, Trinity College Dublin, College Green, Dublin 2 (Ireland); Donnelly, Alison, E-mail: donnelac@tcd.ie [Centre for the Environment, School of Natural Sciences, Trinity College Dublin (Ireland); Jones, Mike, E-mail: mike.jones@tcd.ie [Discipline of Botany, School of Natural Sciences, Trinity College Dublin (Ireland); Chrysoulakis, Nektarios, E-mail: zedd2@iacm.forth.gr [Foundation for Research and Technology-Hellas, Institute of Applied and Computational Mathematics (Greece); Lopes, Myriam, E-mail: myr@ua.pt [Departamento de Ambiente e Ordenamento and CESAM, University of Aveiro (Portugal)

2013-01-15

Urban metabolism components define the energy and material exchanges within a city and, therefore, can provide valuable information on the environmental quality of urban areas. Assessing the potential impact of urban planning alternatives on urban metabolism components (such as energy, water, carbon and pollutants fluxes) can provide a quantitative estimation of their sustainability performance. Urban metabolism impact assessment can, therefore, contribute to the identification of sustainable urban structures with regards, for example, to building types, materials and layout, as well as to location and capacity of transportation and infrastructural developments. In this way, it enables the formulation of planning and policy recommendations to promote efficient use of resources and enhance environmental quality in urban areas. The European FP7 project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) has developed a decision-support system (DSS) that systematically integrates urban metabolism components into impact assessment processes with the aim of accurately quantifying the potential effects of proposed planning interventions. The DSS enables integration of multiple spatial and non-spatial datasets (e.g. physical flows of energy and material with variables of social and economic change) in a systematic manner to obtain spatially defined assessment results and to thus inform planners and decision-makers. This multi-criteria approach also enables incorporation of stakeholders' perceptions in order to prioritise decisive assessment criteria. This paper describes the methodological framework used to develop the DSS and critically examines the results of its practical application in five European cities. - Highlights: Black-Right-Pointing-Pointer Urban metabolism in sustainability assessment of planning alternatives. Black-Right-Pointing-Pointer European FP7 project applied to 5 real life case studies across Europe. Black

A decision-support system for sustainable urban metabolism in Europe

International Nuclear Information System (INIS)

González, Ainhoa; Donnelly, Alison; Jones, Mike; Chrysoulakis, Nektarios; Lopes, Myriam

2013-01-01

Urban metabolism components define the energy and material exchanges within a city and, therefore, can provide valuable information on the environmental quality of urban areas. Assessing the potential impact of urban planning alternatives on urban metabolism components (such as energy, water, carbon and pollutants fluxes) can provide a quantitative estimation of their sustainability performance. Urban metabolism impact assessment can, therefore, contribute to the identification of sustainable urban structures with regards, for example, to building types, materials and layout, as well as to location and capacity of transportation and infrastructural developments. In this way, it enables the formulation of planning and policy recommendations to promote efficient use of resources and enhance environmental quality in urban areas. The European FP7 project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) has developed a decision-support system (DSS) that systematically integrates urban metabolism components into impact assessment processes with the aim of accurately quantifying the potential effects of proposed planning interventions. The DSS enables integration of multiple spatial and non-spatial datasets (e.g. physical flows of energy and material with variables of social and economic change) in a systematic manner to obtain spatially defined assessment results and to thus inform planners and decision-makers. This multi-criteria approach also enables incorporation of stakeholders' perceptions in order to prioritise decisive assessment criteria. This paper describes the methodological framework used to develop the DSS and critically examines the results of its practical application in five European cities. - Highlights: ► Urban metabolism in sustainability assessment of planning alternatives. ► European FP7 project applied to 5 real life case studies across Europe. ► Decision support system enables incorporating scientific

Biocompatibility of metal injection molded versus wrought ASTM F562 (MP35N) and ASTM F1537 (CCM) cobalt alloys.

Science.gov (United States)

Chen, Hao; Sago, Alan; West, Shari; Farina, Jeff; Eckert, John; Broadley, Mark

2011-01-01

We present a comparative analysis between biocompatibility test results of wrought and Metal Injection Molded (MIM) ASTM F562-02 UNS R30035 (MP35N) and F1537 UNS R31538 (CCM) alloy samples that have undergone the same generic orthopedic implant's mechanical, chemical surface pre-treatment, and a designed pre-testing sample preparation method. Because the biocompatibility properties resulting from this new MIM cobalt alloy process are not well understood, we conducted tests to evaluate cytotoxicity (in vitro), hemolysis (in vitro), toxicity effects (in vivo), tissue irritation level (in vivo), and pyrogenicity count (in vitro) on such samples. We show that our developed MIM MP35N and CCM materials and treatment processes are biocompatible, and that both the MIM and wrought samples, although somewhat different in microstructure and surface, do not show significant differences in biocompatibility.

In situ dynamics of O2, pH and cyanobacterial transcripts associated with CCM, photosynthesis and detoxification of ROS

DEFF Research Database (Denmark)

Jensen, Sheila I; Steunou, Anne-Soisig; Bhaya, Devaki

2011-01-01

The relative abundance of transcripts encoding proteins involved in inorganic carbon concentrating mechanisms (CCM), detoxification of reactive oxygen species (ROS) and photosynthesis in the thermophilic cyanobacterium Synechococcus OS-B' was measured in hot spring microbial mats over two diel...

Exercise as an intervention for the age-related decline in brain metabolic support

Directory of Open Access Journals (Sweden)

Brenda J Anderson

2010-08-01

Full Text Available To identify interventions for brain aging, we must first identify the processes in which we hope to intervene. Brain aging is a period of decreasing functional capacity and increasing vulnerability, which reflect a reduction in morphological organization and perhaps degeneration. Since life is ultimately dependent upon the ability to maintain cellular organization through metabolism, this review explores evidence for a decline in neural metabolic support during aging, which includes a reduction in whole brain cerebral blood flow, and cellular metabolic capacity. Capillary density may also decrease with age, although the results are less clear. Exercise may be a highly effective intervention for brain aging, because it improves the cardiovascular system as a whole, and increases regional capillary density and neuronal metabolic capacity. Although the evidence is strongest for motor regions, more work may yield additional evidence for exercise-related improvement in metabolic support in non-motor regions. The protective effects of exercise may be specific to brain region and the type of insult. For example, exercise protects striatal cells from ischemia, but it produces mixed results after hippocampal seizures. Exercise can improve metabolic support and bioenergetic capacity in adult animals, but it remains to be determined whether it has similar effects in aging animals. What is clear is that exercise can influence the multiple levels of support necessary for maintaining optimal neuronal function, which is unique among proposed interventions for aging.

Analysis of Low-Speed Stall Aerodynamics of a Business Jets Wing Using STAR-CCM+

Science.gov (United States)

Bui, Trong

2016-01-01

Reynolds-Averaged Navier-Stokes (RANS) computational fluid dynamics (CFD) analysis was conducted: to study the low-speed stall aerodynamics of a GIII aircrafts swept wing modified with (1) a laminar-flow wing glove, or (2) a seamless flap. The stall aerodynamics of these two different wing configurations were analyzed and compared with the unmodified baseline wing for low-speed flight. The Star-CCM+ polyhedral unstructured CFD code was first validated for wing stall predictions using the wing-body geometry from the First AIAA CFD High-Lift Prediction Workshop.

Effects of velocity and weight support on ground reaction forces and metabolic power during running.

Science.gov (United States)

Grabowski, Alena M; Kram, Rodger

2008-08-01

The biomechanical and metabolic demands of human running are distinctly affected by velocity and body weight. As runners increase velocity, ground reaction forces (GRF) increase, which may increase the risk of an overuse injury, and more metabolic power is required to produce greater rates of muscular force generation. Running with weight support attenuates GRFs, but demands less metabolic power than normal weight running. We used a recently developed device (G-trainer) that uses positive air pressure around the lower body to support body weight during treadmill running. Our scientific goal was to quantify the separate and combined effects of running velocity and weight support on GRFs and metabolic power. After obtaining this basic data set, we identified velocity and weight support combinations that resulted in different peak GRFs, yet demanded the same metabolic power. Ideal combinations of velocity and weight could potentially reduce biomechanical risks by attenuating peak GRFs while maintaining aerobic and neuromuscular benefits. Indeed, we found many combinations that decreased peak vertical GRFs yet demanded the same metabolic power as running slower at normal weight. This approach of manipulating velocity and weight during running may prove effective as a training and/or rehabilitation strategy.

Economic evaluation of Cardiac Contractility Modulation (CCM therapy with the optimizer IVs in the management of heart failure patients

Directory of Open Access Journals (Sweden)

Nikos Maniadakis

2015-01-01

The present analysis indicates that CCM may be cost-effective therapy. This early conclusion should be viewed in the light of the caveats of the modeling methods used, due to data availability limitations. Long-term studies directly collecting hospitalization and mortality data should be undertaken to provide more robust evidence.

Basal metabolic state governs AIF-dependent growth support in pancreatic cancer cells

International Nuclear Information System (INIS)

Scott, Andrew J.; Wilkinson, Amanda S.; Wilkinson, John C.

2016-01-01

Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. In addition to supporting the survival of healthy cells, AIF also plays a contributory role to the development of cancer through its enzymatic activity, and we have previously shown that AIF preferentially supports advanced-stage prostate cancer cells. Here we further evaluated the role of AIF in tumorigenesis by exploring its function in pancreatic cancer, a disease setting that most often presents at an advanced stage by the time of diagnosis. A bioinformatics approach was first employed to investigate AIF mRNA transcript levels in pancreatic tumor specimens vs. normal tissues. AIF-deficient pancreatic cancer cell lines were then established via lentiviral infection. Immunoblot analysis was used to determine relative protein quantities within cells. Cell viability was measured by flow cytometry; in vitro and Matrigel™ growth/survival using Coulter™ counting and phase contrast microscopy; and glucose consumption in the absence and presence of Matrigel™ using spectrophotometric methods. Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. AIF expression was then suppressed in a panel of five pancreatic cancer cell lines that display diverse metabolic phenotypes. AIF ablation selectively crippled the growth of cells in vitro in a manner that directly correlated with the loss of mitochondrial respiratory chain subunits and altered glucose metabolism, and these effects were exacerbated in the presence of Matrigel™ substrate. This suggests a critical metabolic role for AIF to pancreatic tumorigenesis, while the spectrum of sensitivities to AIF ablation depends on basal cellular metabolic phenotypes. Altogether these data indicate that AIF supports the growth and survival of metabolically defined

Gender difference in the association between social support and metabolic syndrome in Japan: the 'enkai' effect?

Science.gov (United States)

Ikeda, Ai; Kawachi, Ichiro; Iso, Hiroyasu; Inoue, Manami; Tsugane, Shoichiro

2011-01-01

Recent reports have found an association between social support and reduced prevalence of metabolic syndrome (or its components) in the West; however, no study has been carried out in Asian populations. The authors examined 12,537 men and women who were part of the Japan Public Health Center-based Prospective Study initiated in 1993. Perceived emotional support was assessed through questionnaire as receipt of confidant support and esteem support from family members or friends. Metabolic syndrome was defined based on the modified criteria of the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and International Diabetes Federation (IDF), while its components were obtained through health examinations conducted during the same year as the questionnaire. The authors found an association between social support and metabolic syndrome among Japanese men that was in the opposite direction to what has previously been reported in western studies. Among men, the multivariate ORs and 95% CIs for metabolic syndrome in the lowest versus highest level of social support was 0.75 (0.58 to 0.97) based on AHA/NHLBI criteria and 0.69 (0.51 to 0.92) based on IDF criteria. Among women, the authors found no association between social support and metabolic syndrome. In this study, men with higher social support appeared to engage in heavier drinking and also reported a higher fat intake pattern, both of which may increase the risk of metabolic syndrome mainly through overweight. Our findings lend weight to the notion that the pattern of association between social support and health outcomes is both culturally contingent and gender-specific.

FOREWORD: CCM Second International Seminar: Pressure Metrology from 1 kPa to 1 GPa

Science.gov (United States)

Molinar, G. F.

1994-01-01

, it was at a high level. This special issue of Metrologia brings together all the seminar papers accepted for publication after a careful review process controlled directly by the organizing committee of the seminar and the Metrologia editor. I feel that we have succeeded reasonably well. The papers published here focus on important achievements in pressure measurements and the main problems which the scientific community is working to resolve in the future. Various achievements are reported, ranging from a general improvement in accuracy to new devices and techniques. I would like to thank all those who helped with this seminar. First, the members of the organizing committee: Chairman of the CCM Medium Pressure Work ing Group, P Stuart, (NPL, UK); J Bonhoure (BIPM); V Borovkov (VNIIFTRI, Russia); C Ehrlich (NIST, USA); J Jager (PTB, Germany); J C Legras (LNE); Chairman of the CCM Low Pressure Working Group, C Tilford (NIST, USA); S Yamamoto (NRLM, Japan); R Wirniewski (WUT, Poland); not forgetting the institutions that allowed them to spend considerable time on the preparation and organization of the seminar. I extend my thanks to V E Bean (NIST, USA), A Ooiwa (NRLM, Japan), and A J Rostocki (WUT, Poland), who joined the organizing committee as guest editors and helped to see the papers presented at the seminar through the review process and into print. Many thanks are also due to A Bryden, Director of the Laboratoire National d'Essais, and to J C Legras of the LNE Pressure Laboratory, for hosting the seminar and for taking care of all practical problems. A special thanks to T J Quinn, Director of the Bureau International des Poids et Mesures, for his continuous support and encouragement in the preparation of the seminar. Grateful thanks to Desgranges et Huot, France, for their hospitality in Paris; and to D-H Instruments Co., USA, and Ruska Co., USA, which sponsored the seminar through their fmancial support for the publication of these Proceedings. A special

How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

Directory of Open Access Journals (Sweden)

Sarah Sonnay

2017-05-01

Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

Science.gov (United States)

Kabakyenga, Jerome; Barigye, Celestine; Brenner, Jennifer; Maling, Samuel; Buchner, Denise; Nettle-Aquirre, Alberto; Singhal, Nalini; Kyomuhangi, Teddy; Tumusiime, David; Finch, Janet; MacLeod, Stuart

2016-03-01

Benefits of mobile phone deployment for children mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

Science.gov (United States)

Horne, Michael R.; Madaras, Eric I.

2010-01-01

Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

Assessing Intraseasonal Variability Produced by Several Deep Convection Schemes in the NCAR CCM3.6

Science.gov (United States)

Maloney, E. D.

2001-05-01

The Hack, Zhang/McFarlane, and McRAS convection schemes produce very different simulations of intraseasonal variability in the NCAR CCM3.6. A robust analysis of simulation performance requires an expanded set of diagnostics. The use of only one criterion to analyze model Madden-Julian oscillation (MJO) variability, such as equatorial zonal wind variability, may give a misleading impression of model performance. Schemes that produce strong variability in zonal winds may sometimes lack a corresponding coherent signal in precipitation, suggesting that model convection and the large-scale circulation are not as strongly coupled as observed. The McRAS scheme, which includes a parametrization of unsaturated convective downdrafts, produces the best simulation of intraseasonal variability of the three schemes used. Downdrafts in McRAS create a moister equatorial troposphere, which increases equatorial convection. Composite analysis indicates a strong dependence of model intraseasonal variability on the frictional convergence mechanism, which may also be important in nature. The McRAS simulation has limitations, however. Indian Ocean variability is weak, and anomalous convection extends too far east across the Pacific. The dependence of convection on surface friction is too strong, and causes enhanced MJO convection to be associated with low-level easterly wind perturbations, unlike observed MJO convection. Anomalous vertical advection associated with surface convergence influences model convection by moistening the lower troposphere. Based on the work of Hendon (2000), coupling to an interactive ocean is unlikely to change the performance of the CCM3 with McRAS, due to the phase relationship between anomalous convection and zonal winds. Use of the analysis tools presented here indicates areas for improvement in the parametrization of deep convection by atmospheric GCMs.

Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

Science.gov (United States)

Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

2017-09-05

Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

Science.gov (United States)

Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

2016-08-25

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

Simulation of the modern arctic climate by the NCAR CCM1

Science.gov (United States)

Bromwich, David H.; Tzeng, Ren-Yow; Parish, Thomas, R.

1994-01-01

The National Center of Atmospheric Research (NCAR) Community Climate Model Version 1 (CCM1's) simulation of the modern arctic climate is evaluated by comparing a five-year seasonal cycle simulation with the European Center for Medium-Range Weather Forecasts (ECMWF) global analyses. The sea level pressure (SLP), storm tracks, vertical cross section of height, 500-hPa height, total energy budget, and moisture budget are analyzed to investigate the biases in the simulated arctic climate. The results show that the model simulates anomalously low SLP, too much storm activity, and anomalously strong baroclinicity to the west of Greenland and vice versa to the east of Greenland. This bias is mainly attributed to the model's topographic representation of Greenland. First, the broadened Greenland topography in the model distorts the path of cyclone waves over the North Atlantic Ocean. Second, the model oversimulates the ridge over Greenland, which intensifies its blocking effect and steers the cyclone waves clockwise around it and hence produces an artificial circum-Greenland trough. These biases are significantly alleviated when the horizontal resolution increases to T42. Over the Arctic basin, the model simulates large amounts of low-level (stratus) clouds in winter and almost no stratus in summer, which is opposite to the observations. This bias is mainly due to the location of the simulated SLP features and the negative anomaly of storm activity, which prevent the transport of moisture into this region during summer but favor this transport in winter. The moisture budget analysis shows that the model's net annual precipitation (P-E) between 70 deg N and the North Pole is 6.6 times larger than the observations and the model transports six times more moisture into this region. The bias in the advection term is attributed to the positive moisture fixer scheme and the distorted flow pattern. However, the excessive moisture transport into the Arctic basin does not solely

The module CCM for the simulation of the thermal-hydraulic situation within a coolant channel

International Nuclear Information System (INIS)

Hoeld, A.

2000-01-01

A coolant channel module (Cc) will be presented which aim is to simulate, in a very general way, the thermal-hydraulic behaviour of single- and two-phase fluids flowing along a heated (or cooled) vertical, inclined or horizontal coolant channel. It is based on a theoretical drift-flux supported 3-equation mixture-fluid model describing the steady state and transient behaviour of characteristic thermal-hydraulic parameters of a single- and two-phase flow within such a channel. The module can be applied as an element within an overall theoretical model for large and complex plant assemblies (PWR and BWR core channels, parallel channels in 3D cores, primary and secondary sides of different steam generators types etc.). The model refers to a general (basic) coolant channel (BC) which can consists of different flow regimes. The BC has thus to be subdivided accordingly into a number of subchannels (SC-s). All of them can belong, however, to only two types of SC-s (single-phase fluid with subcooled water or superheated steam or a two-phase flow regime). For both of them the possibility of variable entrance or outlet positions has to be considered. For discretization purposes the BC (and thus also the SC-s) have to be subdivided into a number of (BC and SC) nodes, discretizing thus the conservation equations for mass, energy and momentum along these nodes by applying a very general spatial procedure, namely a 'modified finite volume method'. A special quadratic polygon approximation method (PAX procedure) helps then to establish a connection between nodal boundary and mean nodal parameters. Considering their constitutive equations (among them an adequate drift-flux correlation package) yields finally a set of non-linear algebraic and non-linear ordinary differential equations for the characteristic parameters of each of these SC nodes (mass flow, pressure drop, coolant temperature and/or void fraction). Based on this theory a code package (CCM) could be established

Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.

Science.gov (United States)

Spinelli, Jessica B; Yoon, Haejin; Ringel, Alison E; Jeanfavre, Sarah; Clish, Clary B; Haigis, Marcia C

2017-11-17

Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment and was used directly to generate amino acids through GDH activity. These data show that ammonia is not only a secreted waste product but also a fundamental nitrogen source that can support tumor biomass. Copyright © 2017, American Association for the Advancement of Science.

Neutron–gamma discrimination based on the support vector machine method

International Nuclear Information System (INIS)

Yu, Xunzhen; Zhu, Jingjun; Lin, ShinTed; Wang, Li; Xing, Haoyang; Zhang, Caixun; Xia, Yuxi; Liu, Shukui; Yue, Qian; Wei, Weiwei; Du, Qiang; Tang, Changjian

2015-01-01

In this study, the combination of the support vector machine (SVM) method with the moment analysis method (MAM) is proposed and utilized to perform neutron/gamma (n/γ) discrimination of the pulses from an organic liquid scintillator (OLS). Neutron and gamma events, which can be firmly separated on the scatter plot drawn by the charge comparison method (CCM), are detected to form the training data set and the test data set for the SVM, and the MAM is used to create the feature vectors for individual events in the data sets. Compared to the traditional methods, such as CCM, the proposed method can not only discriminate the neutron and gamma signals, even at lower energy levels, but also provide the corresponding classification accuracy for each event, which is useful in validating the discrimination. Meanwhile, the proposed method can also offer a predication of the classification for the under-energy-limit events

Effectiveness of using pure copper and silver coupon corrosivity monitoring (CCM) metal strips to measure the severity levels of air pollutants in indoor and outdoor atmospheres

CSIR Research Space (South Africa)

Foax, LJ

2008-10-01

Full Text Available Severity levels of air pollutants rich in oxides, chlorides and sulphides were successfully measured in indoor and outdoor atmospheres using pure copper and silver coupon corrosivity monitoring (CCM) metal strips when the maximum exposure periods...

Montreal Protocol Benefits simulated with CCM SOCOL

Directory of Open Access Journals (Sweden)

T. Egorova

2013-04-01

Full Text Available Ozone depletion is caused by the anthropogenic increase of halogen-containing species in the atmosphere, which results in the enhancement of the concentration of reactive chlorine and bromine in the stratosphere. To reduce the influence of anthropogenic ozone-depleting substances (ODS, the Montreal Protocol was agreed by Governments in 1987, with several Amendments and Adjustments adopted later. In order to assess the benefits of the Montreal Protocol and its Amendments and Adjustments (MPA on ozone and UV radiation, two different runs of the chemistry-climate model (CCM SOCOL have been carried out. The first run was driven by the emission of ozone depleting substances (ODS prescribed according to the restrictions of the MPA. For the second run we allow the ODS to grow by 3% annually. We find that the MPA would have saved up to 80% of the global annual total ozone by the end of the 21st century. Our calculations also show substantial changes of the stratospheric circulation pattern as well as in surface temperature and precipitations that could occur in the world without MPA implementations. To illustrate the changes in UV radiation at the surface and to emphasise certain features, which can only be seen for some particular regions if the influence of the cloud cover changes is accounted for, we calculate geographical distribution of the erythemally weighted irradiance (Eery. For the no Montreal Protocol simulation Eery increases by factor of 4 to 16 between the 1970s and 2100. For the scenario including the Montreal Protocol it is found that UV radiation starts to decrease in 2000, with continuous decline of 5% to 10% at middle latitudes in the both Northern and Southern Hemispheres.

CCM Continuity Constraint Method: A finite-element computational fluid dynamics algorithm for incompressible Navier-Stokes fluid flows

Energy Technology Data Exchange (ETDEWEB)

Williams, P. T. [Univ. of Tennessee, Knoxville, TN (United States)

1993-09-01

As the field of computational fluid dynamics (CFD) continues to mature, algorithms are required to exploit the most recent advances in approximation theory, numerical mathematics, computing architectures, and hardware. Meeting this requirement is particularly challenging in incompressible fluid mechanics, where primitive-variable CFD formulations that are robust, while also accurate and efficient in three dimensions, remain an elusive goal. This dissertation asserts that one key to accomplishing this goal is recognition of the dual role assumed by the pressure, i.e., a mechanism for instantaneously enforcing conservation of mass and a force in the mechanical balance law for conservation of momentum. Proving this assertion has motivated the development of a new, primitive-variable, incompressible, CFD algorithm called the Continuity Constraint Method (CCM). The theoretical basis for the CCM consists of a finite-element spatial semi-discretization of a Galerkin weak statement, equal-order interpolation for all state-variables, a 0-implicit time-integration scheme, and a quasi-Newton iterative procedure extended by a Taylor Weak Statement (TWS) formulation for dispersion error control. Original contributions to algorithmic theory include: (a) formulation of the unsteady evolution of the divergence error, (b) investigation of the role of non-smoothness in the discretized continuity-constraint function, (c) development of a uniformly H¹ Galerkin weak statement for the Reynolds-averaged Navier-Stokes pressure Poisson equation, (d) derivation of physically and numerically well-posed boundary conditions, and (e) investigation of sparse data structures and iterative methods for solving the matrix algebra statements generated by the algorithm.

Diagnostics of the Tropical Tropopause Layer from in-situ observations and CCM data

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C. M. Volk

2009-12-01

Full Text Available A suite of diagnostics is applied to in-situ aircraft measurements and one Chemistry-Climate Model (CCM data to characterize the vertical structure of the Tropical Tropopause Layer (TTL. The diagnostics are based on vertical tracer profiles and relative vertical tracer gradients, using tropopause-referenced coordinates, and tracer-tracer relationships in the tropical Upper Troposphere/Lower Stratosphere (UT/LS.

Observations were obtained during four tropical campaigns performed from 1999 to 2006 with the research aircraft Geophysica and have been compared to the output of the ECHAM5/MESSy CCM. The model vertical resolution in the TTL (~500 m allows for appropriate comparison with high-resolution aircraft observations and the diagnostics used highlight common TTL features between the model and the observational data.

The analysis of the vertical profiles of water vapour, ozone, and nitrous oxide, in both the observations and the model, shows that concentration mixing ratios exhibit a strong gradient change across the tropical tropopause, due to the role of this latter as a transport barrier and that transition between the tropospheric and stratospheric regimes occurs within a finite layer. The use of relative vertical ozone and carbon monoxide gradients, in addition to the vertical profiles, helps to highlight the region where this transition occurs and allows to give an estimate of its thickness. The analysis of the CO-O₃ and H₂O-O₃ scatter plots and of the Probability Distribution Function (PDF of the H₂O-O₃ pair completes this picture as it allows to better distinguish tropospheric and stratospheric regimes that can be identified by their different chemical composition.

The joint analysis and comparison of observed and modelled data allows to state that the model can represent the background TTL structure and its seasonal variability rather accurately. The model

Predicting metabolic syndrome using decision tree and support vector machine methods

Directory of Open Access Journals (Sweden)

Farzaneh Karimi-Alavijeh

2016-06-01

Full Text Available BACKGROUND: Metabolic syndrome which underlies the increased prevalence of cardiovascular disease and Type 2 diabetes is considered as a group of metabolic abnormalities including central obesity, hypertriglyceridemia, glucose intolerance, hypertension, and dyslipidemia. Recently, artificial intelligence based health-care systems are highly regarded because of its success in diagnosis, prediction, and choice of treatment. This study employs machine learning technics for predict the metabolic syndrome. METHODS: This study aims to employ decision tree and support vector machine (SVM to predict the 7-year incidence of metabolic syndrome. This research is a practical one in which data from 2107 participants of Isfahan Cohort Study has been utilized. The subjects without metabolic syndrome according to the ATPIII criteria were selected. The features that have been used in this data set include: gender, age, weight, body mass index, waist circumference, waist-to-hip ratio, hip circumference, physical activity, smoking, hypertension, antihypertensive medication use, systolic blood pressure (BP, diastolic BP, fasting blood sugar, 2-hour blood glucose, triglycerides (TGs, total cholesterol, low-density lipoprotein, high density lipoprotein-cholesterol, mean corpuscular volume, and mean corpuscular hemoglobin. Metabolic syndrome was diagnosed based on ATPIII criteria and two methods of decision tree and SVM were selected to predict the metabolic syndrome. The criteria of sensitivity, specificity and accuracy were used for validation. RESULTS: SVM and decision tree methods were examined according to the criteria of sensitivity, specificity and accuracy. Sensitivity, specificity and accuracy were 0.774 (0.758, 0.74 (0.72 and 0.757 (0.739 in SVM (decision tree method. CONCLUSION: The results show that SVM method sensitivity, specificity and accuracy is more efficient than decision tree. The results of decision tree method show that the TG is the most

Predicting metabolic syndrome using decision tree and support vector machine methods.

Science.gov (United States)

Karimi-Alavijeh, Farzaneh; Jalili, Saeed; Sadeghi, Masoumeh

2016-05-01

Metabolic syndrome which underlies the increased prevalence of cardiovascular disease and Type 2 diabetes is considered as a group of metabolic abnormalities including central obesity, hypertriglyceridemia, glucose intolerance, hypertension, and dyslipidemia. Recently, artificial intelligence based health-care systems are highly regarded because of its success in diagnosis, prediction, and choice of treatment. This study employs machine learning technics for predict the metabolic syndrome. This study aims to employ decision tree and support vector machine (SVM) to predict the 7-year incidence of metabolic syndrome. This research is a practical one in which data from 2107 participants of Isfahan Cohort Study has been utilized. The subjects without metabolic syndrome according to the ATPIII criteria were selected. The features that have been used in this data set include: gender, age, weight, body mass index, waist circumference, waist-to-hip ratio, hip circumference, physical activity, smoking, hypertension, antihypertensive medication use, systolic blood pressure (BP), diastolic BP, fasting blood sugar, 2-hour blood glucose, triglycerides (TGs), total cholesterol, low-density lipoprotein, high density lipoprotein-cholesterol, mean corpuscular volume, and mean corpuscular hemoglobin. Metabolic syndrome was diagnosed based on ATPIII criteria and two methods of decision tree and SVM were selected to predict the metabolic syndrome. The criteria of sensitivity, specificity and accuracy were used for validation. SVM and decision tree methods were examined according to the criteria of sensitivity, specificity and accuracy. Sensitivity, specificity and accuracy were 0.774 (0.758), 0.74 (0.72) and 0.757 (0.739) in SVM (decision tree) method. The results show that SVM method sensitivity, specificity and accuracy is more efficient than decision tree. The results of decision tree method show that the TG is the most important feature in predicting metabolic syndrome. According

Health benefits observed after probiotic Lactobacillus fermentum CCM 7421 application in dogs.

Science.gov (United States)

Strompfová, Viola; Kubašová, Ivana; Lauková, Andrea

2017-08-01

The importance of the intestinal microbiota has attracted much interest in recent years particularly with respect to ways in which the microbiota can be manipulated in order to improve health. Improving gut health through the use of probiotic microorganisms has become an area of research activity in both human and animal nutrition. However, the amount of research using companion animals is insufficient. The present review evaluates and compares the effects achieved after application of canine-derived probiotic strain Lactobacillus fermentum CCM 7421 to healthy dogs as well as to dogs suffering from gastrointestinal disorders. The experiments involved varying duration of application (4 days-14 days), dosage (10 7 -10 9  CFU), form of application (fresh culture or lyophilized from) or combination with natural substances. Results from nine independent studies show the ability of probiotic strains to establish themselves in the canine gastrointestinal tract, alter the composition of intestinal microbiota and metabolites (organic acids), and modulate the physiology (serum biochemical parameters) and immunity parameters in dogs. Almost all observed effects were irrespective of dose or duration of probiotic administration.

Introduction of mobile phones for use by volunteer community health workers in support of integrated community case management in Bushenyi District, Uganda: development and implementation process.

Science.gov (United States)

Tumusiime, David Katuruba; Agaba, Gad; Kyomuhangi, Teddy; Finch, Jan; Kabakyenga, Jerome; MacLeod, Stuart

2014-01-01

A substantial literature suggests that mobile phones have great potential to improve management and survival of acutely ill children in rural Africa. The national strategy of the Ugandan Ministry of Health calls for employment of volunteer community health workers (CHWs) in implementation of Integrated Community Case Management (iCCM) of common illnesses (diarrhea, acute respiratory infection, pneumonia, fever/malaria) affecting children under five years of age. A mobile phone enabled system was developed within iCCM aiming to improve access by CHWs to medical advice and to strengthen reporting of data on danger signs and symptoms for acutely ill children under five years of age. Herein critical steps in development, implementation, and integration of mobile phone technology within iCCM are described. Mechanisms to improve diagnosis, treatment and referral of sick children under five were defined. Treatment algorithms were developed by the project technical team and mounted and piloted on the mobile phones, using an iterative process involving technical support personnel, health care providers, and academic support. Using a purposefully developed mobile phone training manual, CHWs were trained over an intensive five-day course to make timely diagnoses, recognize clinical danger signs, communicate about referrals and initiate treatment with appropriate essential drugs. Performance by CHWs and the accuracy and completeness of their submitted data was closely monitored post training test period and during the subsequent nine month community trial. In the full trial, the number of referrals and correctly treated children, based on the agreed treatment algorithms, was recorded. Births, deaths, and medication stocks were also tracked. Seven distinct phases were required to develop a robust mobile phone enabled system in support of the iCCM program. Over a nine month period, 96 CHWs were trained to use mobile phones and their competence to initiate a community trial was

The eHealth Enhanced Chronic Care Model: a theory derivation approach.

Science.gov (United States)

Gee, Perry M; Greenwood, Deborah A; Paterniti, Debora A; Ward, Deborah; Miller, Lisa M Soederberg

2015-04-01

Chronic illnesses are significant to individuals and costly to society. When systematically implemented, the well-established and tested Chronic Care Model (CCM) is shown to improve health outcomes for people with chronic conditions. Since the development of the original CCM, tremendous information management, communication, and technology advancements have been established. An opportunity exists to improve the time-honored CCM with clinically efficacious eHealth tools. The first goal of this paper was to review research on eHealth tools that support self-management of chronic disease using the CCM. The second goal was to present a revised model, the eHealth Enhanced Chronic Care Model (eCCM), to show how eHealth tools can be used to increase efficiency of how patients manage their own chronic illnesses. Using Theory Derivation processes, we identified a "parent theory", the Chronic Care Model, and conducted a thorough review of the literature using CINAHL, Medline, OVID, EMBASE PsychINFO, Science Direct, as well as government reports, industry reports, legislation using search terms "CCM or Chronic Care Model" AND "eHealth" or the specific identified components of eHealth. Additionally, "Chronic Illness Self-management support" AND "Technology" AND several identified eHealth tools were also used as search terms. We then used a review of the literature and specific components of the CCM to create the eCCM. We identified 260 papers at the intersection of technology, chronic disease self-management support, the CCM, and eHealth and organized a high-quality subset (n=95) using the components of CCM, self-management support, delivery system design, clinical decision support, and clinical information systems. In general, results showed that eHealth tools make important contributions to chronic care and the CCM but that the model requires modification in several key areas. Specifically, (1) eHealth education is critical for self-care, (2) eHealth support needs to be

The Evidence-base for Using Ontologies and Semantic Integration Methodologies to Support Integrated Chronic Disease Management in Primary and Ambulatory Care: Realist Review. Contribution of the IMIA Primary Health Care Informatics WG.

Science.gov (United States)

Liyanage, H; Liaw, S-T; Kuziemsky, C; Terry, A L; Jones, S; Soler, J K; de Lusignan, S

2013-01-01

Most chronic diseases are managed in primary and ambulatory care. The chronic care model (CCM) suggests a wide range of community, technological, team and patient factors contribute to effective chronic disease management. Ontologies have the capability to enable formalised linkage of heterogeneous data sources as might be found across the elements of the CCM. To describe the evidence base for using ontologies and other semantic integration methods to support chronic disease management. We reviewed the evidence-base for the use of ontologies and other semantic integration methods within and across the elements of the CCM. We report them using a realist review describing the context in which the mechanism was applied, and any outcome measures. Most evidence was descriptive with an almost complete absence of empirical research and important gaps in the evidence-base. We found some use of ontologies and semantic integration methods for community support of the medical home and for care in the community. Ubiquitous information technology (IT) and other IT tools were deployed to support self-management support, use of shared registries, health behavioural models and knowledge discovery tools to improve delivery system design. Data quality issues restricted the use of clinical data; however there was an increased use of interoperable data and health system integration. Ontologies and semantic integration methods are emergent with limited evidence-base for their implementation. However, they have the potential to integrate the disparate community wide data sources to provide the information necessary for effective chronic disease management.

Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

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Azeddine Bentaib

2015-03-01

Full Text Available 2D-DIGE analysis coupled with mass spectrometry is a global, without a priori, comparative proteomic approach particularly suited to identify and quantify enzymes isoforms and structural proteins, thus making it an efficient tool for the characterization of the changes in cell phenotypes that occur in physiological and pathological conditions. In this data article in support of the research article entitled “Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study” [1] we illustrate the changes in protein profile that occur during the metabolic reprogramming undergone by cultured mouse astrocytes in a model of in-vitro cancerous transformation [2].

An investigation of the Archean climate using the NCAR CCm

International Nuclear Information System (INIS)

Jenkins, G.S.

1991-01-01

The Archean (2.5 to 3.8 billion years ago) is of interest climatically, because of the 'Faint-Young Sun Paradox', which can be characterized by the Sun's reduced energy output. This lower energy output leads to a frozen planet if the climate existed as it does today. But, the geologic record shows that water was flowing at the earth's surface 3.8 billion years ago. Energy Balance Models (EBMs) and one-dimensional radiative-convective (1DRC) models predict a frozen planet for this time period, unless large carbon dioxide (CO2) concentrations exist in the Archean atmosphere. The goal is to explore the Archean climate with the National Center for Atmospheric Research (NCAR), Community Climate Model (CCM). The search for negative feedbacks to explain the 'Faint-Young Sun Paradox' is the thrust of this study. This study undertakes a series of sensitivity simulations which first explores individual factors that may be important for the Archean. They include rotation rate, lower solar luminosity, and land fraction. Then, these climatic factors along with higher CO2 concentrations are combined into a set of experiments. A faster rotation rate may have existed in the Archean. The faster rotation rate simulations show warmer globally averaged surface temperatures that are caused by a 20 percent decrease in the total cloud fraction. The smaller cloud fraction is brought about by dynamical changes. A global ocean is a possibility for the Archean. A global ocean simulation predicts 4 K increase in global mean surface temperatures compared to the present-day climate control

Comparison of the seasonal climate simulated by the pattern CCM3 and the data of the reanalysis NCEP/NCAR with the observed data of the temperature of the air and the precipitation in Colombia

International Nuclear Information System (INIS)

Leon Aristizabal, Gloria Esperanza; Zea Mazo, Jorge Anibal

2001-01-01

In this work we carry out a comparison of the simulations of the climatic model CCM3, the data of the NCEP/NCAR Reanalysis and real data, by the practical significance of the model based on the observed differences

Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

Science.gov (United States)

Baslow, Morris H

2010-11-01

N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

Reduction of statistic scale applied to data of the CCM3 to generate data of temperature of the air in surface

International Nuclear Information System (INIS)

Molina Lizcano Alicia; Bernal Suarez, Nestor Ricardo; Martinez Collantes, Jorge; Pabon Jose Daniel; Vega Rodriguez, Emel

2000-01-01

The technique is applied of statistical down scaling to find the relations between the variables simulated by a Climate Community Model, in its third version (CCM3) available on the closest grid points near three stations in the Guajira region in north-eastern Colombia, and the surface temperature at those stations. As training (or calibrating)period we chose the years from 1969 to 1990, while the phase of assessment was from 1991 to 1998. The method used was the canonical correlation analysis (CCA) The results were good insofar as the relations obtained approximate satisfactorily the real behaviour of the surface air temperature at the three stations

Modulators of arginine metabolism support cancer immunosurveillance

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Freschi Massimo

2009-01-01

Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

Energy Technology Data Exchange (ETDEWEB)

Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

2013-02-01

Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

Assessment of a simplified set of momentum closure relations for low volume fraction regimes in STAR-CCM+ and OpenFOAM

International Nuclear Information System (INIS)

Sugrue, Rosemary; Magolan, Ben; Lubchenko, Nazar; Baglietto, Emilio

2017-01-01

Highlights: •A simplified set of momentum closures – Bubbly And Moderate void Fraction (BAMF) – is proposed. •BAMF model is assessed by simulation of 12 cases from the Liu and Bankoff experimental database. •Portability between STAR-CCM+ and OpenFOAM CFD softwares is demonstrated. •Both CFD softwares yield mean flow predictions in close agreement with experimental results. -- Abstract: Multiphase computational fluid dynamics (M-CFD) modeling approaches provide three-dimensional resolution of complex two-phase flow and boiling heat transfer phenomena, which makes them an invaluable tool for nuclear reactor design applications. By virtue of the Eulerian-Eulerian spatial and temporal averaging framework, additional terms manifest in the phase momentum equations that require closure through prescription of interfacial forces in the stream-wise and lateral flow directions, as well as in the near-wall region. These momentum closures are critical to M-CFD prediction of mean flow profiles, including velocity and volume fraction distributions, and yet while an overwhelming number of them has been developed, no consensus exists on how to assemble them to achieve a simplified set of closures that is numerically robust and extensible to a wide array of flow configurations; further, no consistent demonstration has been shown of the cross-code portability of these closures between CFD softwares. To address these challenges, we propose in this work a simplified set of momentum closures for stream-wise drag and lateral redistribution mechanisms—collectively referred to as the Bubbly And Moderate void Fraction (BAMF) model—and assess its performance by simulation of 12 cases from the Liu and Bankoff experimental database using STAR-CCM+ and OpenFOAM. Both CFD softwares yield mean flow predictions that are in close agreement with the experimental results, and also in close agreement with each other. These results confirm the effectiveness of the BAMF model and its

The S-layer homology domain-containing protein SlhA from Paenibacillus alvei CCM 2051(T) is important for swarming and biofilm formation.

Science.gov (United States)

Janesch, Bettina; Koerdt, Andrea; Messner, Paul; Schäffer, Christina

2013-01-01

Swarming and biofilm formation have been studied for a variety of bacteria. While this is well investigated for Gram-negative bacteria, less is known about Gram-positive bacteria, including Paenibacillus alvei, a secondary invader of diseased honeybee colonies infected with Melissococcus pluton, the causative agent of European foulbrood (EFB). Paenibacillus alvei CCM 2051(T) is a Gram-positive bacterium which was recently shown to employ S-layer homology (SLH) domains as cell wall targeting modules to display proteins on its cell surface. This study deals with the newly identified 1335-amino acid protein SlhA from P. alvei which carries at the C‑terminus three consecutive SLH-motifs containing the predicted binding sequences SRGE, VRQD, and LRGD instead of the common TRAE motif. Based on the proof of cell surface location of SlhA by fluorescence microscopy using a SlhA-GFP chimera, the binding mechanism was investigated in an in vitro assay. To unravel a putative function of the SlhA protein, a knockout mutant was constructed. Experimental data indicated that one SLH domain is sufficient for anchoring of SlhA to the cell surface, and the SLH domains of SlhA recognize both the peptidoglycan and the secondary cell wall polymer in vitro. This is in agreement with previous data from the S-layer protein SpaA, pinpointing a wider utilization of that mechanism for cell surface display of proteins in P. alvei. Compared to the wild-type bacterium ΔslhA revealed changed colony morphology, loss of swarming motility and impaired biofilm formation. The phenotype was similar to that of the flagella knockout Δhag, possibly due to reduced EPS production influencing the functionality of the flagella of ΔslhA. This study demonstrates the involvement of the SLH domain-containing protein SlhA in swarming and biofilm formation of P. alvei CCM 2051(T).

The S-layer homology domain-containing protein SlhA from Paenibacillus alvei CCM 2051(T is important for swarming and biofilm formation.

Directory of Open Access Journals (Sweden)

Bettina Janesch

Full Text Available Swarming and biofilm formation have been studied for a variety of bacteria. While this is well investigated for Gram-negative bacteria, less is known about Gram-positive bacteria, including Paenibacillus alvei, a secondary invader of diseased honeybee colonies infected with Melissococcus pluton, the causative agent of European foulbrood (EFB.Paenibacillus alvei CCM 2051(T is a Gram-positive bacterium which was recently shown to employ S-layer homology (SLH domains as cell wall targeting modules to display proteins on its cell surface. This study deals with the newly identified 1335-amino acid protein SlhA from P. alvei which carries at the C‑terminus three consecutive SLH-motifs containing the predicted binding sequences SRGE, VRQD, and LRGD instead of the common TRAE motif. Based on the proof of cell surface location of SlhA by fluorescence microscopy using a SlhA-GFP chimera, the binding mechanism was investigated in an in vitro assay. To unravel a putative function of the SlhA protein, a knockout mutant was constructed. Experimental data indicated that one SLH domain is sufficient for anchoring of SlhA to the cell surface, and the SLH domains of SlhA recognize both the peptidoglycan and the secondary cell wall polymer in vitro. This is in agreement with previous data from the S-layer protein SpaA, pinpointing a wider utilization of that mechanism for cell surface display of proteins in P. alvei. Compared to the wild-type bacterium ΔslhA revealed changed colony morphology, loss of swarming motility and impaired biofilm formation. The phenotype was similar to that of the flagella knockout Δhag, possibly due to reduced EPS production influencing the functionality of the flagella of ΔslhA.This study demonstrates the involvement of the SLH domain-containing protein SlhA in swarming and biofilm formation of P. alvei CCM 2051(T.

CONFERENCE NOTE: Comité Consultatif pour la Masse et les grandeurs apparentées (CCM), High Pressure and Medium Pressure Working Groups, Second International Seminar on Pressure Metrology from 1 kPa to 1 GPa

Science.gov (United States)

1992-01-01

The seminar will be held from 2 to 4 June 1993, preceding the next meeting of the CCM, at the Laboratoire National d'Essais (LNE), 1 rue Gaston Boissier, 75015 Paris, France. Scope of the Seminar The purpose of the seminar is to review the state of the art of pressure measurements in the 1 kPa to 1 GPa range and to present original and innovative contributions from standards laboratories and industry. Main Topics The seminar will be organized in six sessions as follows: Liquid-column manometers Piston gauge pressure standards Properties of liquids and gases relevant to pressure metrology Pressure transducers and transfer standards Pressure standard comparison (methods and results) Dynamic pressure measurements. Each topic will be introduced by a review paper presented by a session chairman. A final session, coordinated by Dr G F Molinar (IMGC), Chairman of the CCM High Pressure Working Group, and Dr P Stuart (NPL), Chairman of the CCM Medium Pressure Working Group, will deal with: Actual limits of accuracy of static pressure measurements in fluid media Fundamental problems in pressure metrology between I kPa and 1 GPa. Call for Papers Papers should be prepared for oral presentation and will be refereed by the session chairmen. The Proceedings will be published as a special issue of Metrologia. Papers should be written according to the instructions for authors printed on the inside back cover of this journal. A one-page abstract should be sent to Dr Molinar at the IMGC, to arrive before 31 January 1993. A participation fee of 900 FFr (175 US) will be charged. This will cover general expenses and a copy of the Proceedings. Hotel reservations, meals and transport are not included. Organizers For further information please contact: 1993 CCM Pressure Seminar, Dr G F Molinar, Istituto di Metrologia "G Colonnetti", Strada delle Cacce 73, 1-10135 Torino, Italy telephone (39) 11 39771; telex 212209 IMGCTO-I; fax (39) 11 346761. Contact at the LNE: J C Legras, telephone (33

Plausible role for CHW peer support groups in increasing care-seeking in an integrated community case management project in Rwanda: a mixed methods evaluation

Science.gov (United States)

Langston, Anne; Weiss, Jennifer; Landegger, Justine; Pullum, Thomas; Morrow, Melanie; Kabadege, Melene; Mugeni, Catherine; Sarriot, Eric

2014-01-01

ABSTRACT Background: The Kabeho Mwana project (2006–2011) supported the Rwanda Ministry of Health (MOH) in scaling up integrated community case management (iCCM) of childhood illness in 6 of Rwanda's 30 districts. The project trained and equipped community health workers (CHWs) according to national guidelines. In project districts, Kabeho Mwana staff also trained CHWs to conduct household-level health promotion and established supervision and reporting mechanisms through CHW peer support groups (PSGs) and quality improvement systems. Methods: The 2005 and 2010 Demographic and Health Surveys were re-analyzed to evaluate how project and non-project districts differed in terms of care-seeking for fever, diarrhea, and acute respiratory infection symptoms and related indicators. We developed a logit regression model, controlling for the timing of the first CHW training, with the district included as a fixed categorical effect. We also analyzed qualitative data from the final evaluation to examine factors that may have contributed to improved outcomes. Results: While there was notable improvement in care-seeking across all districts, care-seeking from any provider for each of the 3 conditions, and for all 3 combined, increased significantly more in the project districts. CHWs contributed a larger percentage of consultations in project districts (27%) than in non-project districts (12%). Qualitative data suggested that the PSG model was a valuable sub-level of CHW organization associated with improved CHW performance, supervision, and social capital. Conclusions: The iCCM model implemented by Kabeho Mwana resulted in greater improvements in care-seeking than those seen in the rest of the country. Intensive monitoring, collaborative supervision, community mobilization, and CHW PSGs contributed to this success. The PSGs were a unique contribution of the project, playing a critical role in improving care-seeking in project districts. Effective implementation of iCCM

Analysis of the behavior of the flow of refrigerant through the bottom head and the impact of the removal of holes in the side panel of the MAEF-2012 with the code CFD STAR-CCM+; Analisis del comportamiento del flujo de refrigerante a traves del cabezal inferior y el impacto de la supresion de los taladros en el faldon lateral del MAEF-2012 con el codigo CFD STAR-CCM+

Energy Technology Data Exchange (ETDEWEB)

Barrera, J.; Corpa, R.

2013-07-01

The scope of this work consists in the study of different pairs of lower headers with a dynamical code detail like the STAR-CCM + v8, to identify and study the consequences of changes in the distribution of flow and variation in the pressure drop of fluid passing through them, as well as check the absence of impact from the point of view of safety.

Attitudes of anesthesiology residents toward critical care medicine training.

Science.gov (United States)

Durbin, C G; McLafferty, C L

1993-09-01

The number of anesthesiology residents pursuing critical care medicine (CCM) fellowship training has been decreasing in recent years. A significant number of training positions remain unfilled each year. Possible causes of this decline were evaluated by surveying residents regarding their attitudes toward practice and training in CCM. All 38 anesthesiology programs having accredited CCM fellowships were surveyed. Four of these and one program without CCM fellowships were used to develop the survey instrument. Four programs without CCM fellowships and 34 programs with CCM fellowships make up the survey group. Returned were 640 surveys from 37 (97%) programs accounting for over 30% of the possible residents. Resident interest in pursuing CCM training decreased as year of residency increased (P questions suggested resident concerns with the following: stress of chronic care, financial consequences of additional year of training, ICU call frequency and load, ICU role ambiguity, and shared decision-making in the ICU. A recurring question was, "Are there jobs (outside of academics) for anesthesiologist intensivists?" Most residents knew a CCM anesthesiologist they admired and knew that there were unfilled fellowship positions available. Defining the job market, improving curriculum and teaching, supporting deferment of student loans, and introducing residents and medical students to the ICU earlier may increase the interest in CCM practice among anesthesiology residents.

Transport and Use of Bicarbonate in Plants: Current Knowledge and Challenges Ahead

Directory of Open Access Journals (Sweden)

Charlotte Poschenrieder

2018-05-01

Full Text Available Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO3− may further contribute to carbon concentration mechanisms (CCM. This is especially relevant in the CO2-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis of terrestrial plants can also benefit from CCM as evidenced by the evolution of C4 and Crassulacean Acid Metabolism (CAM. The presence of HCO3− in all organisms leads to more questions regarding the mechanisms of uptake and membrane transport in these different biological systems. This review aims to provide an overview of the transport and metabolic processes related to HCO3− in microalgae, macroalgae, seagrasses, and terrestrial plants. HCO3− transport in cyanobacteria and human cells is much better documented and is included for comparison. We further comment on the metabolic roles of HCO3− in plants by focusing on the diversity and functions of carbonic anhydrases and PEP carboxylases as well as on the signaling role of CO2/HCO3− in stomatal guard cells. Plant responses to excess soil HCO3− is briefly addressed. In conclusion, there are still considerable gaps in our knowledge of HCO3− uptake and transport in plants that hamper the development of breeding strategies for both more efficient CCM and better HCO3− tolerance in crop plants.

Transport and Use of Bicarbonate in Plants: Current Knowledge and Challenges Ahead.

Science.gov (United States)

Poschenrieder, Charlotte; Fernández, José Antonio; Rubio, Lourdes; Pérez, Laura; Terés, Joana; Barceló, Juan

2018-05-03

Bicarbonate plays a fundamental role in the cell pH status in all organisms. In autotrophs, HCO₃ − may further contribute to carbon concentration mechanisms (CCM). This is especially relevant in the CO₂-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis of terrestrial plants can also benefit from CCM as evidenced by the evolution of C₄ and Crassulacean Acid Metabolism (CAM). The presence of HCO₃ − in all organisms leads to more questions regarding the mechanisms of uptake and membrane transport in these different biological systems. This review aims to provide an overview of the transport and metabolic processes related to HCO₃ − in microalgae, macroalgae, seagrasses, and terrestrial plants. HCO₃ − transport in cyanobacteria and human cells is much better documented and is included for comparison. We further comment on the metabolic roles of HCO₃ − in plants by focusing on the diversity and functions of carbonic anhydrases and PEP carboxylases as well as on the signaling role of CO₂/HCO₃ − in stomatal guard cells. Plant responses to excess soil HCO₃ − is briefly addressed. In conclusion, there are still considerable gaps in our knowledge of HCO₃ − uptake and transport in plants that hamper the development of breeding strategies for both more efficient CCM and better HCO₃ − tolerance in crop plants.

VRML metabolic network visualizer.

Science.gov (United States)

Rojdestvenski, Igor

2003-03-01

A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

International Nuclear Information System (INIS)

Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

2014-01-01

Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

Energy Technology Data Exchange (ETDEWEB)

Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R. [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Jijakli, Kenan [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Engineering Division, Biofinery, Manhattan, KS (United States); Salehi-Ashtiani, Kourosh, E-mail: ksa3@nyu.edu [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates)

2014-12-10

Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

Genome scale metabolic modeling of cancer

DEFF Research Database (Denmark)

Nilsson, Avlant; Nielsen, Jens

2017-01-01

of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

[Development of quality of care indicators to support chronic disease management].

Science.gov (United States)

Beaulieu, Marie-dominique; Pomey, Marie-pascale; Del Grande, Claudio; Côté, Brigitte; Tremblay, Éric; Ghorbel, Monia; Hua, Phuong

2015-01-01

This article presents the results of a project conducted by the Institut national d'excellence en santé et en services sociaux of Québec to develop quality of care indicators for the management of six chronic illnesses. Indicators were identified through literature searches and analysis of clinical practice guidelines (CPGs). Interdisciplinary expert panels assessed their validity and the strength of the evidence on which they were based. Representatives of patients (N = 19) and professionals (N = 29) were consulted on their relevance and acceptability. Indicators were categorized according to the Chronic Care Model (CCM). A total of 164 indicators were developed, 126 specific to the illnesses under study and 38 on processes and outcomes generic to the CCM. There was convergence between patients and professionals on the relevance of a majority of indicators. Professionals expressed concerns on the indicators measured by means of patient surveys that they considered to be too subjective. The importance given to CPGs as the main source of indicators resulted in a great number of indicators of the technical quality ofcare. Using the CCM contributed to a broader perspective of quality. The consultation process identified some of the concerns of professionals about indicator measurement, thusguidingfuture implementation initiatives.

Immune-Challenged Fish Up-Regulate Their Metabolic Scope to Support Locomotion.

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Camille Bonneaud

Full Text Available Energy-based trade-offs occur when investment in one fitness-related trait diverts energy away from other traits. The extent to which such trade-offs are shaped by limits on the rate of conversion of energy ingested in food (e.g. carbohydrates into chemical energy (ATP by oxidative metabolism rather than by the amount of food ingested in the first place is, however, unclear. Here we tested whether the ATP required for mounting an immune response will lead to a trade-off with ATP available for physical activity in mosquitofish (Gambusia holbrooki. To this end, we challenged fish either with lipopolysaccharide (LPS from E. coli or with Sheep Red Blood Cells (SRBC, and measured oxygen consumption at rest and during swimming at maximum speed 24h, 48h and 7 days post-challenge in order to estimate metabolic rates. Relative to saline-injected controls, only LPS-injected fish showed a significantly greater resting metabolic rate two days post-challenge and significantly higher maximal metabolic rates two and seven days post-challenge. This resulted in a significantly greater metabolic scope two days post-challenge, with LPS-fish transiently overcompensating by increasing maximal ATP production more than would be required for swimming in the absence of an immune challenge. LPS-challenged fish therefore increased their production of ATP to compensate physiologically for the energetic requirements of immune functioning. This response would avoid ATP shortages and allow fish to engage in an aerobically-challenging activity (swimming even when simultaneously mounting an immune response. Nevertheless, relative to controls, both LPS- and SRBC-fish displayed reduced body mass gain one week post-injection, and LPS-fish actually lost mass. The concomitant increase in metabolic scope and reduced body mass gain of LPS-challenged fish indicates that immune-associated trade-offs are not likely to be shaped by limited oxidative metabolic capacities, but may instead

Effective Reading Comprehension in EFL Contexts: Individual and Collaborative Concept Mapping Strategies

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Zahra Riahi

2017-02-01

Full Text Available The present study attempted to investigate the possible impacts of Individual Concept Mapping (ICM and Collaborative Concept Mapping (CCM strategies on Iranian EFL learners' reading comprehension. For this purpose, 90 pre-intermediate female language learners ranged between 12 to 17 years of age were selected to randomly assign into ICM, CCM and Control groups in this study. After taking Key English Test (KET, the ICM and CCM groups received EFL reading materials presented and practiced with ICM and CCM strategies, respectively, while the Control group received only conventional instructions to reading comprehension. After conducting the treatment, all participants took a Concept Mapping post-test constructed by the researchers. The hypothetical assumptions in this study were in favor of ICM and CCM strategies to improve the Iranian EFL learners’ reading comprehension. Statistics supported the outperformance of the ICM and CCM groups comparing to Control group who received convention PPP teaching techniques on Concept Mapping post-test. However, the superiority of neither strategies was statistically proved so that no meaningful difference between the reading comprehension of the ICM and CCM groups were detected. Therefore, the researchers failed to determine which strategy caused a better or higher impact. Some pedagogical implications and recommended topics for further research were provided to the motivated researchers.

L3:PHI.CMD.P13.02 Support for CILC L1 Milestone Using STAR-CCM+

International Nuclear Information System (INIS)

Slattery, Stuart R.; Gurecky, William L.

2016-01-01

This report documents work performed to support Consortium for the Advanced Simulation of LWRs (CASL) modeling of Chalk River Unidentified Deposit (CRUD) Induced Power Shift (CIPS) and CRUD Induced Local Corrosion (CILC) using the Cicada package. The work documented here is intended to complement current and future CIPS and CILC modeling activities in CASL. We provide tools for crud and corrosion-related simulation and analysis by developing a better understanding of the interplay between the coupled physics that describe the phenomena at different time and length scales. We intend to use these models to better inform future simulation capability and development.

L3:PHI.CMD.P13.02 Support for CILC L1 Milestone Using STAR-CCM+

Energy Technology Data Exchange (ETDEWEB)

Slattery, Stuart R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gurecky, William L. [Univ. of Texas, Austin, TX (United States)

2016-10-07

This report documents work performed to support Consortium for the Advanced Simulation of LWRs (CASL) modeling of Chalk River Unidentified Deposit (CRUD) Induced Power Shift (CIPS) and CRUD Induced Local Corrosion (CILC) using the Cicada package. The work documented here is intended to complement current and future CIPS and CILC modeling activities in CASL. We provide tools for crud and corrosion-related simulation and analysis by developing a better understanding of the interplay between the coupled physics that describe the phenomena at different time and length scales. We intend to use these models to better inform future simulation capability and development.

Policy challenges facing integrated community case management in Sub-Saharan Africa.

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Bennett, Sara; George, Asha; Rodriguez, Daniela; Shearer, Jessica; Diallo, Brahima; Konate, Mamadou; Dalglish, Sarah; Juma, Pamela; Namakhoma, Ireen; Banda, Hastings; Chilundo, Baltazar; Mariano, Alda; Cliff, Julie

2014-07-01

To report an in-depth analysis of policy change for integrated community case management of childhood illness (iCCM) in six sub-Saharan African countries. We analysed how iCCM policies developed and the barriers and facilitators to policy change. Qualitative retrospective case studies drawing from document reviews, semi-structured interviews and in-country validation workshops were conducted in Burkina Faso, Kenya, Malawi, Mali, Mozambique and Niger. These countries were selected to maximise variation in iCCM policy status, community health worker (CHW) models and different African regions. Country iCCM policies evolved in an ad hoc fashion, but were substantially influenced by the history of primary health care and the nature of CHW programmes. Technical officers within Ministries of Health led iCCM policy change with support from international donors, but neither communities nor political leadership was mobilised. Concerns about achieving the Millennium Development Goals, together with recognition of the shortcomings of existing child health programmes, led to the adoption of iCCM policies. Availability of external financing played a critical role in facilitating policy change. iCCM policy change has been promoted by international agencies, but national governments have struggled to align iCCM with country health systems. Greater investment is needed in tailoring global policy initiatives to match country needs. High-level, political ownership of iCCM policies could facilitate policy change, as could clearer strategies for ensuring the long-term sustainability of such policies. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Brucella microti sp. nov., isolated from the common vole Microtus arvalis.

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Scholz, Holger C; Hubalek, Zdenek; Sedlácek, Ivo; Vergnaud, Gilles; Tomaso, Herbert; Al Dahouk, Sascha; Melzer, Falk; Kämpfer, Peter; Neubauer, Heinrich; Cloeckaert, Axel; Maquart, Marianne; Zygmunt, Michel S; Whatmore, Adrian M; Falsen, Enevold; Bahn, Peter; Göllner, Cornelia; Pfeffer, Martin; Huber, Birgit; Busse, Hans-Jürgen; Nöckler, Karsten

2008-02-01

Two Gram-negative, non-motile, non-spore-forming, coccoid bacteria (strains CCM 4915(T) and CCM 4916), isolated from clinical specimens of the common vole Microtus arvalis during an epizootic in the Czech Republic in 2001, were subjected to a polyphasic taxonomic study. On the basis of 16S rRNA (rrs) and recA gene sequence similarities, both isolates were allocated to the genus Brucella. Affiliation to Brucella was confirmed by DNA-DNA hybridization studies. Both strains reacted equally with Brucella M-monospecific antiserum and were lysed by the bacteriophages Tb, Wb, F1 and F25. Biochemical profiling revealed a high degree of enzyme activity and metabolic capabilities not observed in other Brucella species. The omp2a and omp2b genes of isolates CCM 4915(T) and CCM 4916 were indistinguishable. Whereas omp2a was identical to omp2a of brucellae from certain pinniped marine mammals, omp2b clustered with omp2b of terrestrial brucellae. Analysis of the bp26 gene downstream region identified strains CCM 4915(T) and CCM 4916 as Brucella of terrestrial origin. Both strains harboured five to six copies of the insertion element IS711, displaying a unique banding pattern as determined by Southern blotting. In comparative multilocus VNTR (variable-number tandem-repeat) analysis (MLVA) with 296 different genotypes, the two isolates grouped together, but formed a separate cluster within the genus Brucella. Multilocus sequence typing (MLST) analysis using nine different loci also placed the two isolates separately from other brucellae. In the IS711-based AMOS PCR, a 1900 bp fragment was generated with the Brucella ovis-specific primers, revealing that the insertion element had integrated between a putative membrane protein and cboL, encoding a methyltransferase, an integration site not observed in other brucellae. Isolates CCM 4915(T) and CCM 4916 could be clearly distinguished from all known Brucella species and their biovars by means of both their phenotypic and molecular

Surgical Management and Long-Term Seizure Outcome After Surgery for Temporal Lobe Epilepsy Associated with Cerebral Cavernous Malformations.

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Yang, Peng-Fan; Pei, Jia-Sheng; Jia, Yan-Zeng; Lin, Qiao; Xiao, Hui; Zhang, Ting-Ting; Zhong, Zhong-Hui

2018-02-01

Operative strategies for cerebral cavernous malformation (CCM)-associated temporal lobe epilepsy and timing of surgical intervention continue to be debated. This study aimed to establish an algorithm to evaluate the efficacy of surgical intervention strategies, to maximize positive surgical outcomes and minimize postsurgical neurologic deficits. 47 patients having undergone operation for CCM-associated temporal lobe epilepsy were retrospectively reviewed. They had received a diagnostic series for seizure localization, including long-term video electroencephalography (vEEG), high-resolution magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). In patients with mesial temporal lobe CCMs, the involved structures (amygdala, hippocampus, or parahippocampal gyrus) were resected in addition to the lesions. Patients with neocortical epileptogenic CCM underwent extended lesionectomy guided by intraoperative electrocorticography; further performance of amygdalohippocampectomy depended on the extent of hippocampal epileptogenicity. The study cohort contained 28 patients with drug-resistant epilepsy (DRE), 12 with chronic epilepsy (CE), and 7 with sporadic seizure (SS). Normal temporal lobe metabolism was seen in 7/7 patients of the SS group. Hypometabolism was found in all patients with chronic disease except for those with posterior inferior and middle temporal gyrus cavernous malformations (CMs). Of the 31 patients with superficial neocortical CCM, 7 had normal PET without hippocampal sclerosis, 14 had ipsilateral temporal lobe hypometabolism without hippocampal sclerosis, and 10 had obvious hippocampal sclerosis and hypometabolism. Seizure freedom in DRE, CE, and SS was 82.1%, 75%, and 100%, respectively. A significant difference was found between lesion laterality and postoperative seizure control; the rate was lower in left-sided cases because of less aggressive resection. Our study demonstrates that the data from the

Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

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Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

2014-05-01

Bay of Bengal (BoB), a low productive part of the North Indian Ocean, often possesses low CO2 levels in its surface water and diatoms dominate the phytoplankton communities. Virtually no studies are available from this area reporting how this diatom dominated phytoplankton community would respond any increase in dissolved CO2 levels either naturally or anthopogenically. In most of the marine phytoplankton, the inefficiency of the sole carbon fixing enzyme Rubisco necessitates the need of concentrating dissolved inorganic carbon (DIC) (mostly as HCO3) inside the cell in excess of the ambient water concentrations in order to maintain high rate of photosynthesis under low CO2 levels through an energy consuming carbon concentration mechanisms (CCMs). The ubiquitous enzyme carbonic anhydrase (CA) plays a vital role in CCMs by converting HCO3- to CO2 and usually utilizes the trace metal zinc (Zn) as a cofactor. However, it is evident in many marine phytoplankton species that with increasing external CO2 levels, CCMs can be down-regulated leading to energetic savings which can be reallocated to growth; although exceptions occur. Hence, in order to predict their responses to the projected changes, it is imperative to understand their carbon metabolism patterns. We have conducted a series of incubation experiments in microcosms with natural phytoplankton communities from the coastal waters of BoB under different CO2 levels. Our results revealed that the rate of net photosynthetic oxygen evolution and biomass build-up increased in response to increasing CO2 levels. The depletion in δ13CPOM values were more in the high CO2 treatments relative to the low CO2 treated cells (control), indicating that dissolved CO2 uptake was higher when CO2 levels were increased. When additional Zn was added to the low CO2 treated cells, net photosynthetic oxygen evolution rate was increased significantly than that of the untreated control. It is likely that upon the supply of Zn under low CO2

E+ subgroup PPR protein defective kernel 36 is required for multiple mitochondrial transcripts editing and seed development in maize and Arabidopsis.

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Wang, Gang; Zhong, Mingyu; Shuai, Bilian; Song, Jiandong; Zhang, Jie; Han, Liang; Ling, Huiling; Tang, Yuanping; Wang, Guifeng; Song, Rentao

2017-06-01

Mitochondria are semi-autonomous organelles that are the powerhouse of the cells. Plant mitochondrial RNA editing guided by pentatricopeptide repeat (PPR) proteins is essential for energy production. We identify a maize defective kernel mutant dek36, which produces small and collapsed kernels, leading to embryos and/or seedlings lethality. Seed filling in dek36 is drastically impaired, in line with the defects observed in the organization of endosperm transfer tissue. Positional cloning reveals that DEK36, encoding a mitochondria-targeted E+ subgroup PPR protein, is required for mitochondrial RNA editing at atp4-59, nad7-383 and ccmF N -302, thus resulting in decreased activities of mitochondrial complex I, complex III and complex IV in dek36. Loss-of-function of its Arabidopsis ortholog At DEK36 causes arrested embryo and endosperm development, leading to embryo lethality. At_dek36 also has RNA editing defects in atp4, nad7, ccmF N 1 and ccmF N 2 , but at the nonconserved sites. Importantly, efficiency of all editing sites in ccmF N 1 , ccmF N 2 and rps12 is severely decreased in At_dek36, probably caused by the impairment of their RNA stabilization. These results suggest that the DEK36 orthologue pair are essential for embryo and endosperm development in both maize and Arabidopsis, but through divergent function in regulating RNA metabolism of their mitochondrial targets. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Evaluating Diabetes Care for Patients With Serious Mental Illness Using the Chronic Care Model

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Kelly Vaez

2017-10-01

Full Text Available People with serious mental illness (SMI have a higher incidence of type 2 diabetes mellitus (T2DM and shorter life span due to medical health problems. The chronic care model (CCM has been used to improve care of patients with T2DM. One clinical organization that provided primary care to patients with SMI had excellent diabetes outcomes but did not have information on how they achieved those outcomes. Thus, we conducted a pilot study chart review for 30 patients with T2DM and SMI to determine how well the clinic’s system aligned with the overall CCM components and which components correlated with diabetes control. We also evaluated use of the CCM using the Assessment of Chronic Illness Care provider survey. Results showed that the clinic had an overall basic implementation level of the CCM, which allows opportunity for improvement. Two elements of the CCM were correlated with hemoglobin A 1C and both were in an unexpected direction: self-management support in the variable of percentage of visits that included patient-specific goal-setting ( r s = .52; P = .004 and delivery system design in the variable of number of nurse practitioner visits per study period ( r s = .43; P = .02. These findings suggest that the clinic may have made more concentrated efforts to manage diabetes for patients who were not in good diabetes control. Providers noted the influence of SMI and social service organization support on these patients’ clinical outcomes. The findings will be reexamined after a fuller implementation of the CCM to further improve management in this population.

Stakeholders' perceptions of integrated community case management by community health workers: a post-intervention qualitative study.

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Denise L Buchner

Full Text Available Integrated community case management (iCCM involves delivery of simple medicines to children with pneumonia, diarrhea and/or malaria by community health workers (CHWs. Between 2010 and 2012, an iCCM intervention trial was implemented by Healthy Child Uganda. This study used qualitative tools to assess whether project stakeholders perceived that iCCM improved access to care for children under five years of age.The intervention involved training and equipping 196 CHWs in 98 study villages in one sub-county in Uganda in iCCM. During the eight-month intervention, CHWs assessed sick children, provided antimalarials (coartem for fever, antibiotics (amoxicillin for cough and fast breathing, oral rehydration salts/zinc for diarrhea, and referred very sick children to health facilities. In order to examine community perceptions and acceptability of iCCM, post-intervention focus groups and key respondent interviews involving caregivers, health workers, CHWs and local leaders were carried out by experienced facilitators using semi-structured interview guides. Data were analyzed using thematic analysis techniques.Respondents reported increased access to health care for children as a result of iCCM. Access was reportedly closer to home, available more hours in a day, and the availability of CHWs was perceived as more reliable. CHW care was reported to be trustworthy and caring. Families reported saving money especially due to reduced transportation costs, and less time away from home. Respondents also perceived better health outcomes. Linkages between health facilities and communities were reportedly improved by the iCCM intervention due to the presence of trained CHWs in the community.iCCM delivered by CHWs may improve access to health care and is acceptable to families. Policymakers should continue to seek opportunities to implement and support iCCM, particularly in remote communities where there are health worker shortages.

Metabolic modelling to support long term strategic decisions on water supply systems

Science.gov (United States)

Ciriello, Valentina; Felisa, Giada; Lauriola, Ilaria; Pomanti, Flavio; Di Federico, Vittorio

2017-04-01

Water resources are essential for the economic development and sustenance of anthropic activities belonging to the civil, agricultural and industrial sectors. Nevertheless, availability of water resources is not uniformly distributed in space and time. Moreover, the increasing water demand, mainly due to population growth and expansion of agricultural crops, may cause increasing water stress conditions, if combined with the effects of climate change. Under these circumstances, it is necessary to improve the resilience of water supply systems both in terms of infrastructures and environmental compliance. Metabolic modelling approaches represent a flexible tool able to provide support to decision making in the long term, based on sustainability criteria. These approaches mimic the water supply network through a set of material and energy fluxes that interact and influence each other. By analyzing these fluxes, a suite of key performance indicators is evaluated in order to identify which kind of interventions may be applied to increase the sustainability of the system. Here, we adopt these concepts to analyze the water supply network of Reggio-Emilia (Italy) which is supported by water withdrawals from both surface water and groundwater bodies. We analyze different scenarios, including possible reduction of water withdrawals from one of the different sources as a consequence of a decrease in water availability under present and future scenarios. On these basis, we identify preventive strategies for a dynamic management of the water supply system.

Regulatory components of carbon concentrating mechanisms in aquatic unicellular photosynthetic organisms.

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Tomar, Vandana; Sidhu, Gurpreet Kaur; Nogia, Panchsheela; Mehrotra, Rajesh; Mehrotra, Sandhya

2017-11-01

This review provides an insight into the regulation of the carbon concentrating mechanisms (CCMs) in lower organisms like cyanobacteria, proteobacteria, and algae. CCMs evolved as a mechanism to concentrate CO 2 at the site of primary carboxylating enzyme Ribulose-1, 5-bisphosphate carboxylase oxygenase (Rubisco), so that the enzyme could overcome its affinity towards O 2 which leads to wasteful processes like photorespiration. A diverse set of CCMs exist in nature, i.e., carboxysomes in cyanobacteria and proteobacteria; pyrenoids in algae and diatoms, the C 4 system, and Crassulacean acid metabolism in higher plants. Prime regulators of CCM in most of the photosynthetic autotrophs belong to the LysR family of transcriptional regulators, which regulate the activity of the components of CCM depending upon the ambient CO 2 concentrations. Major targets of these regulators are carbonic anhydrase and inorganic carbon uptake systems (CO 2 and HCO 3 - transporters) whose activities are modulated either at transcriptional level or by changes in the levels of their co-regulatory metabolites. The article provides information on the localization of the CCM components as well as their function and participation in the development of an efficient CCM. Signal transduction cascades leading to activation/inactivation of inducible CCM components on perception of low/high CO 2 stimuli have also been brought into picture. A detailed study of the regulatory components can aid in identifying the unraveled aspects of these mechanisms and hence provide information on key molecules that need to be explored to further provide a clear understanding of the mechanism under study.

Astrocytes and energy metabolism.

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Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

2011-05-01

Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

Mechanisms of carbon dioxide acquisition and CO2 sensing in marine diatoms: a gateway to carbon metabolism.

Science.gov (United States)

Matsuda, Yusuke; Hopkinson, Brian M; Nakajima, Kensuke; Dupont, Christopher L; Tsuji, Yoshinori

2017-09-05

Diatoms are one of the most successful marine eukaryotic algal groups, responsible for up to 20% of the annual global CO 2 fixation. The evolution of a CO 2 -concentrating mechanism (CCM) allowed diatoms to overcome a number of serious constraints on photosynthesis in the marine environment, particularly low [CO 2 ] aq in seawater relative to concentrations required by the CO 2 fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which is partly due to the slow diffusion rate of CO 2 in water and a limited CO 2 formation rate from [Formula: see text] in seawater. Diatoms use two alternative strategies to take up dissolved inorganic carbon (DIC) from the environment: one primarily relies on the direct uptake of [Formula: see text] through plasma-membrane type solute carrier (SLC) 4 family [Formula: see text] transporters and the other is more reliant on passive diffusion of CO 2 formed by an external carbonic anhydrase (CA). Bicarbonate taken up into the cytoplasm is most likely then actively transported into the chloroplast stroma by SLC4-type transporters on the chloroplast membrane system. Bicarbonate in the stroma is converted into CO 2 only in close proximity to RubisCO preventing unnecessary CO 2 leakage. CAs play significant roles in mobilizing DIC as it is progressively moved towards the site of fixation. However, the evolutionary types and subcellular locations of CAs are not conserved between different diatoms, strongly suggesting that this DIC mobilization strategy likely evolved multiple times with different origins. By contrast, the recent discovery of the thylakoid luminal θ-CA indicates that the strategy to supply CO 2 to RubisCO in the pyrenoid may be very similar to that of green algae, and strongly suggests convergent coevolution in CCM function of the thylakoid lumen not only among diatoms but among eukaryotic algae in general. In this review, both experimental and corresponding theoretical models of the diatom CCMs are

Cancer Cell Metabolism: One Hallmark, Many Faces

OpenAIRE

Cantor, Jason R.; Sabatini, David M.

2012-01-01

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

Low Earth orbit journey and ground simulations studies point out metabolic changes in the ESA life support organism Rhodospirillum rubrum

Science.gov (United States)

Mastroleo, Felice; Leys, Natalie; Benotmane, Rafi; Vanhavere, Filip; Janssen, Ann; Hendrickx, Larissa; Wattiez, Ruddy; Mergeay, Max

MELiSSA (Micro-Ecological Life Support System Alternative) is a project of closed regenerative life support system for future space flights developed by the European Space Agency. It consists of interconnected processes (i.e. bioreactors, higher plant compartments, filtration units,..) targeting the total recycling of organic waste into oxygen, water and food. Within the MELiSSA loop, the purple non-sulfur alpha-proteobacterium R. rubrum ATCC25903 is used to convert fatty acids released from the upstream raw waste digesting reactor to CO2 and biomass, and to complete the mineralization of aminoacids into NH4+ that will be forwarded to the nitrifying compartment. Among the numerous challenges of the project, the functional stability of the bioreactors in long term and under space flight conditions is of paramount importance for the efficiency of the life support system and consequently the crew safety. Therefore, the physiological and metabolic changes induced by space flight were investigated for R. rubrum. The bacterium grown on solid medium during 2 different 10-day space flights to the ISS (MES- SAGE2, BASE-A experiments) were compared to cells grown on Earth 1 g gravity or modeled microgravity and normal Earth radiation or simulated space flight radiation conditions in order to relate each single stress to its respective cellular response. For simulating the radiation environment, pure gamma and neutron sources were combined, while simulation of changes in gravity where performed using the Random Positioning Machine technology. Transcriptome analysis using R. rubrum total genome DNA-chip showed up-regulation of genes involved in oxidative stress response after a 10-day mission inside the ISS, without loss of viability. As an example, alkyl hydroperoxide reductase, thioredoxin reductase and bacterioferritin genes are least 2 fold induced although the radiation dose experienced by the bacterium (4 mSv) is very low compared to its radiotolerance (D10 = 100 Sv

National scale-up of integrated community case management in rural Ethiopia: implementation and early lessons learned.

Science.gov (United States)

2014-10-01

Although under-five mortality in Ethiopia has decreased 67% in the past two decades, many, children still die from preventable or treatable conditions, mainly pneumonia, newborn problems, diarrhea, malaria and malnutrition. Most of these deaths can be avoided with timely and appropriate care, but access to and use of treatment remains inadequate. Community health workers, appropriately trained, supervised, and supplied with essen- tial equipment and medicines, can deliver case management or referral to most sick children. In 2010, Ethiopia added pneumonia to diarrhea, malaria and severe acute malnutrition, targeted for treatment in the integrated community case management (iCCM) strategy. This article describes the national scale-up of iCCM implementation and early lessons learned. We reviewed data related to iCCM program inputs and processes from reports, minutes, and related documents from January 2010 through July 2013. We describe introduction and scale-up through eight health system components. The government and partners trained and supplied 27,116 of the total 32,000 Health Extension Workers and mentored 80% of them to deliver iCCM services to over one million children. The government led a strong-iCCM partnership that attracted development partners in implementation, monitoring, evaluation, and research. Service utilization and weak supply chain remain-major challenges. Strong MOH leadership, policy support, and national partnerships helped successful national iCCM scale-up and should help settle remaining challenges.

Cancer cell metabolism: one hallmark, many faces.

Science.gov (United States)

Cantor, Jason R; Sabatini, David M

2012-10-01

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

The chronic care model and relationships to patient health status and health-related quality of life.

Science.gov (United States)

Hung, Dorothy Y; Glasgow, Russell E; Dickinson, L Miriam; Froshaug, Desireé B; Fernald, Douglas H; Balasubramanian, Bijal A; Green, Larry A

2008-11-01

The chronic care model (CCM) is a system-level framework used to guide quality improvement efforts in health care. However, little is known about its relationship to patient-level health measures. This study describes the implementation of the CCM as adapted for prevention and health behavior counseling in primary care practices, and examines relationships between the CCM and patient health measures, including general health status and health-related quality of life (HRQOL). Baseline data from Round 2 of the Prescription for Health initiative (2005-2007) were used to assess CCM implementation in 57 practices located nationwide. Relationships between the CCM and three separate measures of health among 4735 patients were analyzed in 2007. A hierarchical generalized linear modeling approach to ordinal regression was used to estimate categories of general health status, unhealthy days, and activity-limiting days, adjusting for patient covariates and clustering effects. Outcome variances were significantly accounted for by differences in practice characteristics (pPractices that used individual or group planned visits were more likely to see patients in lower health categories across all measures (OR=0.74-0.81, pPractices that used patient registries, health promotion champions, evidence-based guidelines, publicly reported performance measures, and support for behavior change were associated with higher patient health levels (OR=1.28-1.98, ppractice's implementation of the CCM was significantly related to patient health status and HRQOL. Adapting the CCM for prevention may serve to reorient care delivery toward more proactive behavior change and improvements in patient health outcomes.

Validation of the space fields and the median zonal of the temperature of the air in surface and of the precipitation in Colombia, simulated by the pattern CCM3 and the data of the NCEP/NCAR Reanalysis

International Nuclear Information System (INIS)

Zea Mazo, Jorge Anibal; Leon Aristizabal Gloria Esperanza; Eslava Ramirez, Jesus Antonio

2001-01-01

This work presents an analysis of the basic fields of the surface temperature and the precipitation for the national territory, from two sources of information: the data originated by the national meteorological network and the generated ones at world-wide level by means of the NCEP/NCAR Reanalysis project for the assimilation of data coming from diverse world-wide networks. With them reference scenes are constructed to validate the CCM3 model which is used like tool for the projection of the climatic change in Colombia

Thallium stimulates ethanol production in immortalized hippocampal neurons.

Directory of Open Access Journals (Sweden)

Laura Colombaioni

Full Text Available Lactate and ethanol (EtOH were determined in cell culture medium (CCM of immortalized hippocampal neurons (HN9.10e cell line before and after incubation with Thallium (Tl. This cell line is a reliable, in vitro model of one of the most vulnerable regions of central nervous system. Cells were incubated for 48 h with three different single Tl doses: 1, 10, 100 μg/L (corresponding to 4.9, 49 and 490 nM, respectively. After 48 h, neurons were "reperfused" with fresh CCM every 24/48 h until 7 days after the treatment and the removed CCM was collected and analysed. Confocal microscopy was employed to observe morphological changes. EtOH was determined by head space-solid phase microextraction -gas chromatography -mass spectrometry (HS-SPME-GCMS, lactate by RP-HPLC with UV detection. Tl exposure had significant effects on neuronal growth rate and morphology. The damage degree was dose-dependent. In not exposed cells, EtOH concentration was 0.18 ± 0.013 mM, which represents about 5% of lactate concentration (3.4 ± 0.10 mM. After Tl exposure lactate and EtOH increased. In CCM of 100 and 10 μg/L Tl-treated cells, lactate increased 24 h after reperfusion up to 2 and 3.3 times the control value, respectively. In CCM of 10 and 100 μg/L Tl-treated cells 24 h after reperfusion, EtOH increased up to 0.3 and 0.58 mmol/L. respectively. These results are consistent with significant alterations in energy metabolism, despite the low doses of Tl employed and the relatively short incubation time.

Thallium stimulates ethanol production in immortalized hippocampal neurons.

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Colombaioni, Laura; Onor, Massimo; Benedetti, Edoardo; Bramanti, Emilia

2017-01-01

Lactate and ethanol (EtOH) were determined in cell culture medium (CCM) of immortalized hippocampal neurons (HN9.10e cell line) before and after incubation with Thallium (Tl). This cell line is a reliable, in vitro model of one of the most vulnerable regions of central nervous system. Cells were incubated for 48 h with three different single Tl doses: 1, 10, 100 μg/L (corresponding to 4.9, 49 and 490 nM, respectively). After 48 h, neurons were "reperfused" with fresh CCM every 24/48 h until 7 days after the treatment and the removed CCM was collected and analysed. Confocal microscopy was employed to observe morphological changes. EtOH was determined by head space-solid phase microextraction -gas chromatography -mass spectrometry (HS-SPME-GCMS), lactate by RP-HPLC with UV detection. Tl exposure had significant effects on neuronal growth rate and morphology. The damage degree was dose-dependent. In not exposed cells, EtOH concentration was 0.18 ± 0.013 mM, which represents about 5% of lactate concentration (3.4 ± 0.10 mM). After Tl exposure lactate and EtOH increased. In CCM of 100 and 10 μg/L Tl-treated cells, lactate increased 24 h after reperfusion up to 2 and 3.3 times the control value, respectively. In CCM of 10 and 100 μg/L Tl-treated cells 24 h after reperfusion, EtOH increased up to 0.3 and 0.58 mmol/L. respectively. These results are consistent with significant alterations in energy metabolism, despite the low doses of Tl employed and the relatively short incubation time.

Gastric emptying, glucose metabolism and gut hormones

DEFF Research Database (Denmark)

Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K

2011-01-01

To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carb......To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant...... and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied....

Persuasive user experiences of a health Behavior Change Support System: A 12-month study for prevention of metabolic syndrome.

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Karppinen, Pasi; Oinas-Kukkonen, Harri; Alahäivälä, Tuomas; Jokelainen, Terhi; Keränen, Anna-Maria; Salonurmi, Tuire; Savolainen, Markku

2016-12-01

Obesity has become a severe health problem in the world. Even a moderate 5% weight loss can significantly reduce the prevalence of metabolic syndrome, which can be vital for preventing comorbidities caused by the obesity. Health Behavior Change Support Systems (hBCSS) emphasize an autogenous approach, where an individual uses the system to influence one's own attitude or behavior to achieve his or her own goal. Regardless of promising results, such health interventions technology has often been considered merely as a tool for delivering content that has no effect or value of its own. More research on actual system features is required. The objective of this study is to describe how users perceive persuasive software features designed and implemented into a support system. The research medium in this study is a web-based information system designed as a lifestyle intervention for participants who are at risk of developing a metabolic syndrome or who are already suffering from it. The system was designed closely following the principles of the Persuasive Systems Design (PSD) model and the Behavior Change Support Systems (BCSS) framework. A total of 43 system users were interviewed for this study during and after a 52 week intervention period. In addition, the system's login data and subjects' Body Mass Index (BMI) measures were used to interpret the results. This study explains in detail how the users perceived using the system and its persuasive features. Self-monitoring, reminders, and tunneling were perceived as especially beneficial persuasive features. The need for social support appeared to grow along the duration of the intervention. Unobtrusiveness was found to be very important in all stages of the intervention rather than only at the beginning. Persuasive software features have power to affect individuals' health behaviors. Through their systematicity the PSD model and the BCSS framework provide effective support for the design and development of

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

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Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial distribution and deployment of community-based distributors implementing integrated community case management (iCCM): Geographic information system (GIS) mapping study in three South Sudan states.

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Pratt, Abigail; Dale, Martin; Olivi, Elena; Miller, Jane

2014-12-01

In late 2012 and in conjunction with South Sudan's Ministry of Health - National Malaria Control Program, PSI (Population Services International) conducted a comprehensive mapping exercise to assess geographical coverage of its integrated community case management (iCCM) program and consider scope for expansion. The operational research was designed to provide evidence and support for low-cost mapping and monitoring systems, demonstrating the use of technology to enhance the quality of programming and to allow for the improved allocation of resources through appropriate and need-based deployment of community-based distributors (CBDs). The survey took place over the course of three months and program staff gathered GPS (global positioning system) data, along with demographic data, for over 1200 CBDs and 111 CBD supervisors operating in six counties in South Sudan. Data was collated, cleaned and quality assured, input into an Excel database, and subsequently uploaded to geographic information system (GIS) for spatial analysis and map production. The mapping results showed that over three-quarters of CBDs were deployed within a five kilometer radius of a health facility or another CBD, contrary to program planning and design. Other characteristics of the CBD and CBD supervisor profiles (age, gender, literacy) were more closely matched with other regional programs. The results of this mapping exercise provided a valuable insight into the contradictions found between a program "deployment plan" and the realities observed during field implementation. It also highlighted an important need for program implementers and national-level strategy makers to consider the natural and community-driven diffusion of CBDs, and take into consideration the strength of the local health facilities when developing a deployment plan.

Decision support for large-scale remediation strategies by fused urban metabolism and life cycle assessment

DEFF Research Database (Denmark)

Ohms, Pernille; Andersen, Camilla; Landgren, Mathilde

2018-01-01

Purpose: This paper seeks to identify the most environmental friendly way of conducting a refurbishment of Broendby Strand, with focus on PCB remediation. The actual identification is conducted by comparing four remediation techniques using urban metabolism fused with life cycle assessment (UM......-LCA) in combination with information relating to cost and efficiency of the compared techniques. The methodological goal of our paper is to test UM-LCA as a decision support tool and discuss application of the method in relation to large refurbishment projects. Methods: To assess the environmental performance of PCB......-remediation techniques, the UM-LCA method was applied. By combining UM and LCA methodologies, the total environmental impact potentials of the remediation techniques were calculated. To build an inventory for each technique, we contacted and interviewed experts and studied existing literature, cases, and projects...

Genome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga Chlamydomonas reinhardtii under carbon deprivation.

Directory of Open Access Journals (Sweden)

Flavia Vischi Winck

Full Text Available The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO2], a carbon concentrating mechanism (CCM is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1 gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF and transcription regulator (TR genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene-regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO 2 response regulator 1 and Lcr2 (Low-CO2 response regulator 2, may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome

Modification of curcumin with polyethylene glycol enhances the delivery of curcumin in preadipocytes and its antiadipogenic property.

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Kim, Choon Young; Bordenave, Nicolas; Ferruzzi, Mario G; Safavy, Ahmad; Kim, Kee-Hong

2011-02-09

Conjugation of curcumin (CCM) by polyethylene glycol (PEG) has been previously developed to improve water solubility of the natural form of CCM and its antiproliferative role in some human cancer cell lines. This study examined the cellular uptake kinetics of the natural form of CCM and CCM-PEG. Their cytotoxic effect in proliferating preadipocytes and antiadipogenic property in differentiating preadipocytes had also been investigated. CCM and CCM-PEG were found to be differently absorbed in 3T3-L1 preadipocytes and adipocytes with a limited amount of CCM-PEG absorption in the cell. The improved water solubility of CCM-PEG was correlated with increased cellular retention of CCM in 3T3-L1 cells, particularly in preadipocytes. Consequently, CCM-PEG treatment sensitized proliferating preadipocytes to CCM-induced cell toxicity. Furthermore, incubation of differentiating 3T3-L1 cells with CCM-PEG resulted in improvement of the inhibitory role of CCM in adipocyte differentiation with no toxic effect. These results suggest that pegylation-improved water solubility and cellular retention of CCM may be uniquely useful for improving the delivery of CCM in preadipocytes and its antiadipogenic ability.

Metabolic Diet App Suite for inborn errors of amino acid metabolism.

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Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

2016-03-01

An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright �

LakeMetabolizer: An R package for estimating lake metabolism from free-water oxygen using diverse statistical models

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Winslow, Luke; Zwart, Jacob A.; Batt, Ryan D.; Dugan, Hilary; Woolway, R. Iestyn; Corman, Jessica; Hanson, Paul C.; Read, Jordan S.

2016-01-01

Metabolism is a fundamental process in ecosystems that crosses multiple scales of organization from individual organisms to whole ecosystems. To improve sharing and reuse of published metabolism models, we developed LakeMetabolizer, an R package for estimating lake metabolism from in situ time series of dissolved oxygen, water temperature, and, optionally, additional environmental variables. LakeMetabolizer implements 5 different metabolism models with diverse statistical underpinnings: bookkeeping, ordinary least squares, maximum likelihood, Kalman filter, and Bayesian. Each of these 5 metabolism models can be combined with 1 of 7 models for computing the coefficient of gas exchange across the air–water interface (k). LakeMetabolizer also features a variety of supporting functions that compute conversions and implement calculations commonly applied to raw data prior to estimating metabolism (e.g., oxygen saturation and optical conversion models). These tools have been organized into an R package that contains example data, example use-cases, and function documentation. The release package version is available on the Comprehensive R Archive Network (CRAN), and the full open-source GPL-licensed code is freely available for examination and extension online. With this unified, open-source, and freely available package, we hope to improve access and facilitate the application of metabolism in studies and management of lentic ecosystems.

Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

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Ribas-Latre, Aleix; Eckel-Mahan, Kristin

2016-01-01

Background While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in humans. Studies in other species support this association and generally reveal that feeding that is not in phase with the external light/dark cycle, as often occurs with night or rotating shift workers, is disadvantageous in terms of energy balance. As food is a strong driver of circadian rhythms in the periphery, understanding how nutrient metabolism drives clocks across the body is important for dissecting out why circadian misalignment may produce such metabolic effects. A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. Finally, SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders. Scope of review This article presents a background of the circadian clock components and their interrelated metabolic and transcriptional feedback loops, followed by a review of some recent studies in humans and rodents that address the effects of nutrient metabolism on the circadian clock and vice versa. We focus on studies in which results suggest that nutrients provide an opportunity to restore or, alternatively

Evolutionary bursts in Euphorbia (Euphorbiaceae) are linked with photosynthetic pathway.

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Horn, James W; Xi, Zhenxiang; Riina, Ricarda; Peirson, Jess A; Yang, Ya; Dorsey, Brian L; Berry, Paul E; Davis, Charles C; Wurdack, Kenneth J

2014-12-01

The mid-Cenozoic decline of atmospheric CO2 levels that promoted global climate change was critical to shaping contemporary arid ecosystems. Within angiosperms, two CO2 -concentrating mechanisms (CCMs)-crassulacean acid metabolism (CAM) and C4 -evolved from the C3 photosynthetic pathway, enabling more efficient whole-plant function in such environments. Many angiosperm clades with CCMs are thought to have diversified rapidly due to Miocene aridification, but links between this climate change, CCM evolution, and increased net diversification rates (r) remain to be further understood. Euphorbia (∼2000 species) includes a diversity of CAM-using stem succulents, plus a single species-rich C4 subclade. We used ancestral state reconstructions with a dated molecular phylogeny to reveal that CCMs independently evolved 17-22 times in Euphorbia, principally from the Miocene onwards. Analyses assessing among-lineage variation in r identified eight Euphorbia subclades with significantly increased r, six of which have a close temporal relationship with a lineage-corresponding CCM origin. Our trait-dependent diversification analysis indicated that r of Euphorbia CCM lineages is approximately threefold greater than C3 lineages. Overall, these results suggest that CCM evolution in Euphorbia was likely an adaptive strategy that enabled the occupation of increased arid niche space accompanying Miocene expansion of arid ecosystems. These opportunities evidently facilitated recent, replicated bursts of diversification in Euphorbia. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Development, validation, and utility of an instrument to assess core competencies in the Leadership Education in Neurodevelopmental and Related Disabilities (LEND) program.

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Leff, Stephen S; Baum, Katherine T; Bevans, Katherine B; Blum, Nathan J

2015-02-01

To describe the development and psychometric evaluation of the Core Competency Measure (CCM), an instrument designed to assess professional competencies as defined by the Maternal Child Health Bureau (MCHB) and targeted by Leadership Education in Neurodevelopmental and Related Disabilities (LEND) programs. The CCM is a 44-item self-report measure comprised of six subscales to assess clinical, interdisciplinary, family-centered/cultural, community, research, and advocacy/policy competencies. The CCM was developed in an iterative fashion through participatory action research, and then nine cohorts of LEND trainees (N = 144) from 14 different disciplines completed the CCM during the first week of the training program. A 6-factor confirmatory factor analysis model was fit to data from the 44 original items. After three items were removed, the model adequately fit the data (comparative fit indices = .93, root mean error of approximation = .06) with all factor loadings exceeding .55. The measure was determined to be quite reliable as adequate internal consistency and test-retest reliability were found for each subscale. The instrument's construct validity was supported by expected differences in self-rated competencies among fellows representing various disciplines, and the convergent validity was supported by the pattern of inter-correlations between subscale scores. The CCM appears to be a reliable and valid measure of MCHB core competencies for our sample of LEND trainees. It provides an assessment of key training areas addressed by the LEND program. Although the measure was developed within only one LEND Program, with additional research it has the potential to serve as a standardized tool to evaluate the strengths and limitations of MCHB training, both within and between programs.

Indirect Calorimetry in Mechanically Ventilated Patients

DEFF Research Database (Denmark)

Allingstrup, Matilde Jo; Kondrup, Jens; Perner, Anders

2017-01-01

Background and Aims: The 2 currently available indirect calorimeters, CCM Express Indirect Calorimeter (MedGraphics, St Paul, MN) and Quark RMR ICU Indirect Calorimeter (COSMED, Rome, Italy), have not been validated against a gold standard in mechanically ventilated patients. Our aim was to do so...... using a gold-standard, modified Tissot bell-spirometer method in mechanically ventilated patients who were hemodynamically, respiratory, and metabolically stable. Methods: We studied 30 patients undergoing general anesthesia and major gynecological surgery. We measured oxygen consumption ((Formula...... of 77 (167) with limits of agreement −249 to 404 kcal/d. Conclusions: The QUARK RMR ICU Indirect Calorimeter compared better with the gold standard for values of (Formula presented.) O2 and REE than did the CCM Express Indirect Calorimeter in mechanically ventilated patients who were circulatory...

Nutrigenetics of the lipoprotein metabolism.

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Garcia-Rios, Antonio; Perez-Martinez, Pablo; Delgado-Lista, Javier; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

2012-01-01

It is well known that lipid metabolism is a cornerstone in the development of the commonest important chronic diseases worldwide, such as obesity, cardiovascular disease, or metabolic syndrome. In this regard, the area of lipid and lipoprotein metabolism is one of the areas in which the understanding of the development and progression of those metabolic disorders has been studied in greater depth. Thus, growing evidence has demonstrated that while universal recommendations might be appropriate for the general population, in this area there is great variability among individuals, related to a combination of environmental and genetic factors. Moreover, the interaction between genetic and dietary components has helped in understanding this variability. Therefore, with further study into the interaction between the most important genetic markers or single-nucleotide polymorphisms (SNPs) and diet, it may be possible to understand the variability in lipid metabolism, which could lead to an increase in the use of personalized nutrition as the best support to combat metabolic disorders. This review discusses some of the evidence in which candidate SNPs can affect the key players of lipid metabolism and how their phenotypic manifestations can be modified by dietary intake. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

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Cuperlovic-Culf, Miroslava

2018-01-11

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

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Cuperlovic-Culf, Miroslava

2018-01-01

Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

The role of gut microbiota in human metabolism

NARCIS (Netherlands)

Vrieze, A.

2013-01-01

This thesis supports the hypothesis that gut microbiota can be viewed as an ‘exteriorised organ’ that contributes to energy metabolism and the modulation of our immune system. Following Koch’s postulates, it has now been shown that gut microbiota are associated with metabolic disease and that these

The incidences of oxidative –stress occurrence following two metabolic support measures in critically ill patients

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Mojtaba Mojtahedzadeh

2013-02-01

Full Text Available Background: A high percentage of patients admitted to the intensive care unit (ICU have systemic inflammatory response syndrome (SIRS criteria. Free radicals play an important role in initiation and development of SIRS. The purpose of this study was to assess and compare the molecular changes of cellular antioxidant power in patients with SIRS who received enteral nutrition (EN or EN combined with parenteral nutrition (PN. Methods: Two groups of 10 patients were enrolled in this randomized, controlled clinical trial. Those in the treatment group received EN+PN and the control group received only EN. Venous blood samples were taken just prior to initiation of nutritional support and then 24, 48 and 72 hours following entry into the study for examination of antioxidant parameters including total thiol, total antioxidant capacity and lipid peroxidation. Results: The two supportive regimens had different affects on total antioxidant capacity (P=0.005. In the EN group the amount of total antioxidant capacity was not significantly different in different days (P>0.05, but in the EN+PN group it was significantly different on third and forth days as compared to the first day. The two other parameters had no significant differences between the two groups. Conclusion: These results are suggesting that an increase in oxidative stress bio-markers are not necessarily related to the route of pharmaconutrition and may occur independently during metabolic support measures. Keywords: Parenteral Nutrition, Enteral Nitrition, Systemic Inflammatory Response Syndrome, Oxidative stress

The added value of a mobile application of Community Case Management on referral, re-consultation and hospitalization rates of children aged under 5 years in two districts in Northern Malawi: study protocol for a pragmatic, stepped-wedge cluster-randomized controlled trial.

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Hardy, Victoria; O'Connor, Yvonne; Heavin, Ciara; Mastellos, Nikolaos; Tran, Tammy; O'Donoghue, John; Fitzpatrick, Annette L; Ide, Nicole; Wu, Tsung-Shu Joseph; Chirambo, Griphin Baxter; Muula, Adamson S; Nyirenda, Moffat; Carlsson, Sven; Andersson, Bo; Thompson, Matthew

2017-10-11

There is evidence to suggest that frontline community health workers in Malawi are under-referring children to higher-level facilities. Integrating a digitized version of paper-based methods of Community Case Management (CCM) could strengthen delivery, increasing urgent referral rates and preventing unnecessary re-consultations and hospital admissions. This trial aims to evaluate the added value of the Supporting LIFE electronic Community Case Management Application (SL eCCM App) compared to paper-based CCM on urgent referral, re-consultation and hospitalization rates, in two districts in Northern Malawi. This is a pragmatic, stepped-wedge cluster-randomized trial assessing the added value of the SL eCCM App on urgent referral, re-consultation and hospitalization rates of children aged 2 months and older to up to 5 years, within 7 days of the index visit. One hundred and two health surveillance assistants (HSAs) were stratified into six clusters based on geographical location, and clusters randomized to the timing of crossover to the intervention using simple, computer-generated randomization. Training workshops were conducted prior to the control (paper-CCM) and intervention (paper-CCM + SL eCCM App) in assigned clusters. Neither participants nor study personnel were blinded to allocation. Outcome measures were determined by abstraction of clinical data from patient records 2 weeks after recruitment. A nested qualitative study explored perceptions of adherence to urgent referral recommendations and a cost evaluation determined the financial and time-related costs to caregivers of subsequent health care utilization. The trial was conducted between July 2016 and February 2017. This is the first large-scale trial evaluating the value of adding a mobile application of CCM to the assessment of children aged under 5 years. The trial will generate evidence on the potential use of mobile health for CCM in Malawi, and more widely in other low- and middle

Facilitators and barriers of implementing the chronic care model in primary care: a systematic review.

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Kadu, Mudathira K; Stolee, Paul

2015-02-06

The Chronic Care Model (CCM) is a framework developed to redesign care delivery for individuals living with chronic diseases in primary care. The CCM and its various components have been widely adopted and evaluated, however, little is known about different primary care experiences with its implementation, and the factors that influence its successful uptake. The purpose of this review is to synthesize findings of studies that implemented the CCM in primary care, in order to identify facilitators and barriers encountered during implementation. This study identified English-language, peer-reviewed research articles, describing the CCM in primary care settings. Searches were performed in three data bases: Web of Knowledge, Pubmed and Scopus. Article abstracts and titles were read based on whether they met the following inclusion criteria: 1) studies published after 2003 that described or evaluated the implementation of the CCM; 2) the care setting was primary care; 3) the target population of the study was adults over the age of 18 with chronic conditions. Studies were categorized by reference, study design and methods, participants and setting, study objective, CCM components used, and description of the intervention. The next stage of data abstraction involved qualitative analysis of cited barriers and facilitators using the Consolidating Framework for Research Implementation. This review identified barriers and facilitators of implementation across various primary care settings in 22 studies. The major emerging themes were those related to the inner setting of the organization, the process of implementation and characteristics of the individual healthcare providers. These included: organizational culture, its structural characteristics, networks and communication, implementation climate and readiness, presence of supportive leadership, and provider attitudes and beliefs. These findings highlight the importance of assessing organizational capacity and needs prior

Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP

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Jarmon G. Lees

2017-01-01

Full Text Available Metabolism is central to embryonic stem cell (ESC pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape. Further, the preferential use of glucose and anaplerotic glutamine metabolism serves to not only support cell growth and proliferation but also minimise reactive oxygen species production. However, the perinuclear localisation of spherical, electron-poor mitochondria in ESC is proposed to sustain ESC nuclear-mitochondrial crosstalk and a mitochondrial-H2O2 presence, to facilitate signalling to support self-renewal through the stabilisation of HIFα, a process that may be favoured under physiological oxygen. The environment in which a cell is grown is therefore a critical regulator and determinant of cell fate, with metabolism, and particularly mitochondria, acting as an interface between the environment and the epigenome.

Partitioning the Metabolic Cost of Human Running: A Task-by-Task Approach

Science.gov (United States)

Arellano, Christopher J.; Kram, Rodger

2014-01-01

Compared with other species, humans can be very tractable and thus an ideal “model system” for investigating the metabolic cost of locomotion. Here, we review the biomechanical basis for the metabolic cost of running. Running has been historically modeled as a simple spring-mass system whereby the leg acts as a linear spring, storing, and returning elastic potential energy during stance. However, if running can be modeled as a simple spring-mass system with the underlying assumption of perfect elastic energy storage and return, why does running incur a metabolic cost at all? In 1980, Taylor et al. proposed the “cost of generating force” hypothesis, which was based on the idea that elastic structures allow the muscles to transform metabolic energy into force, and not necessarily mechanical work. In 1990, Kram and Taylor then provided a more explicit and quantitative explanation by demonstrating that the rate of metabolic energy consumption is proportional to body weight and inversely proportional to the time of foot-ground contact for a variety of animals ranging in size and running speed. With a focus on humans, Kram and his colleagues then adopted a task-by-task approach and initially found that the metabolic cost of running could be “individually” partitioned into body weight support (74%), propulsion (37%), and leg-swing (20%). Summing all these biomechanical tasks leads to a paradoxical overestimation of 131%. To further elucidate the possible interactions between these tasks, later studies quantified the reductions in metabolic cost in response to synergistic combinations of body weight support, aiding horizontal forces, and leg-swing-assist forces. This synergistic approach revealed that the interactive nature of body weight support and forward propulsion comprises ∼80% of the net metabolic cost of running. The task of leg-swing at most comprises ∼7% of the net metabolic cost of running and is independent of body weight support and forward

Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy.

Science.gov (United States)

Amoedo, N D; Obre, E; Rossignol, R

2017-08-01

The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [ 13 C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [ 13 C] can also be used to evaluate tumor

Pantothenate kinase 1 is required to support the metabolic transition from the fed to the fasted state.

Directory of Open Access Journals (Sweden)

Roberta Leonardi

2010-06-01

Full Text Available Coenzyme A (CoA biosynthesis is regulated by the pantothenate kinases (PanK, of which there are four active isoforms. The PanK1 isoform is selectively expressed in liver and accounted for 40% of the total PanK activity in this organ. CoA synthesis was limited using a Pank1(-/- knockout mouse model to determine whether the regulation of CoA levels was critical to liver function. The elimination of PanK1 reduced hepatic CoA levels, and fasting triggered a substantial increase in total hepatic CoA in both Pank1(-/- and wild-type mice. The increase in hepatic CoA during fasting was blunted in the Pank1(-/- mouse, and resulted in reduced fatty acid oxidation as evidenced by abnormally high accumulation of long-chain acyl-CoAs, acyl-carnitines, and triglycerides in the form of lipid droplets. The Pank1(-/- mice became hypoglycemic during a fast due to impaired gluconeogenesis, although ketogenesis was normal. These data illustrate the importance of PanK1 and elevated liver CoA levels during fasting to support the metabolic transition from glucose utilization and fatty acid synthesis to gluconeogenesis and fatty acid oxidation. The findings also suggest that PanK1 may be a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia.

SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

Energy Technology Data Exchange (ETDEWEB)

Epstein, T; Xu, L; Gillies, R; Gatenby, R [Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

2014-06-01

Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

International Nuclear Information System (INIS)

Epstein, T; Xu, L; Gillies, R; Gatenby, R

2014-01-01

Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

Inherited metabolic disorders in Thailand.

Science.gov (United States)

Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

2002-08-01

The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

OpenAIRE

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pha...

Effects of independently altering body weight and body mass on the metabolic cost of running.

Science.gov (United States)

Teunissen, Lennart P J; Grabowski, Alena; Kram, Rodger

2007-12-01

The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In the present study, we investigated how independently altering body weight and body mass affects the metabolic cost of running. Based on previous studies, we hypothesized that reducing body weight would decrease metabolic rate proportionally, and adding mass and weight would increase metabolic rate proportionally. Further, because previous studies show that adding mass alone does not affect the forces generated on the ground, we hypothesized that adding mass alone would have no substantial effect on metabolic rate. We manipulated the body weight and body mass of 10 recreational human runners and measured their metabolic rates while they ran at 3 m s(-1). We reduced weight using a harness system, increased mass and weight using lead worn about the waist, and increased mass alone using a combination of weight support and added load. We found that net metabolic rate decreased in less than direct proportion to reduced body weight, increased in slightly more than direct proportion to added load (added mass and weight), and was not substantially different from normal running with added mass alone. Adding mass alone was not an effective method for determining the metabolic cost attributable to braking/propelling body mass. Runners loaded with mass alone did not generate greater vertical or horizontal impulses and their metabolic costs did not substantially differ from those of normal running. Our results show that generating force to support body weight is the primary determinant of the metabolic cost of running. Extrapolating our reduced weight data to zero weight suggests that supporting body weight comprises at most 74% of the net cost of running. However, 74% is probably an

Assessment of a pioneer metabolic information service in Brazil.

Science.gov (United States)

Brustolin, Silvia; Souza, Carolina; Puga, Ana Cristina; Refosco, Lilia; Pires, Ricardo; Peres, Rossana; Giugliani, Roberto

2006-01-01

The Information Service on Inborn Errors of Metabolism (SIEM), a pioneer toll-free service in both Brazil and South America, is based in Porto Alegre, Southern Brazil. SIEM has been operating since October 2001 providing support to health care professionals involved in the diagnosis and management of suspected metabolic diseases. We analyzed the demographic and clinical characteristics of the 376 consults received and followed in the first two and half years of SIEM. Our results show that the suspicion of a metabolic disease was most often associated with neurological symptoms. Among the consults, 24.4% were eventually confirmed as inborn errors of metabolism (IEM), with organic acidurias and amino acid disorders being the two most frequent diagnostic groups. Our conclusion shows this kind of service to provide helpful support to the diagnosis and acute management of IEM, especially to health professionals working in developing countries who are often far from reference centers.

Epigenetics and a new look on metabolic syndrome

Czech Academy of Sciences Publication Activity Database

Kuneš, Jaroslav; Vaněčková, Ivana; Mikulášková, Barbora; Behuliak, Michal; Maletínská, L.; Zicha, Josef

2015-01-01

Roč. 64, č. 5 (2015), s. 611-620 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NV15-25396A; GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : metabolic syndrome * epigenetic s * transgenerational inheritance * gene-environmental interactions * obesity * hypertension Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.643, year: 2015

Multipayer patient-centered medical home implementation guided by the chronic care model.

Science.gov (United States)

Gabbay, Robert A; Bailit, Michael H; Mauger, David T; Wagner, Edward H; Siminerio, Linda

2011-06-01

A unique statewide multipayer ini Pennsylvania was undertaken to implement the Patient-Centered Medical Home (PCMH) guided by the Chronic Care Model (CCM) with diabetes as an initial target disease. This project represents the first broad-scale CCM implementation with payment reform across a diverse range of practice organizations and one of the largest PCMH multipayer initiatives. Practices implemented the CCM and PCMH through regional Breakthrough Series learning collaboratives, supported by Improving Performance in Practice (IPIP) practice coaches, with required monthly quality reporting enhanced by multipayer infrastructure payments. Some 105 practices, representing 382 primary care providers, were engaged in the four regional collaboratives. The practices from the Southeast region of Pennsylvania focused on diabetes patients (n = 10,016). During the first intervention year (May 2008-May 2009), all practices achieved at least Level 1 National Committee for Quality Assurance (NCQA) Physician Practice Connections Patient-Centered Medical Home (PPC-PCMH) recognition. There was significant improvement in the percentage of patients who had evidence-based complications screening and who were on therapies to reduce morbidity and mortality (statins, angiotensin-converting enzyme inhibitors). In addition, there were small but statistically significant improvements in key clinical parameters for blood pressure and cholesterol levels, with the greatest absolute improvement in the highest-risk patients. Transforming primary care delivery through implementation of the PCMH and CCM supported by multipayer infrastructure payments holds significant promise to improve diabetes care.

Linking neuronal brain activity to the glucose metabolism.

Science.gov (United States)

Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

2013-08-29

Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Neuronal Progenitor Maintenance Requires Lactate Metabolism and PEPCK-M-Directed Cataplerosis.

Science.gov (United States)

Álvarez, Zaida; Hyroššová, Petra; Perales, José Carlos; Alcántara, Soledad

2016-03-01

This study investigated the metabolic requirements for neuronal progenitor maintenance in vitro and in vivo by examining the metabolic adaptations that support neuronal progenitors and neural stem cells (NSCs) in their undifferentiated state. We demonstrate that neuronal progenitors are strictly dependent on lactate metabolism, while glucose induces their neuronal differentiation. Lactate signaling is not by itself capable of maintaining the progenitor phenotype. The consequences of lactate metabolism include increased mitochondrial and oxidative metabolism, with a strict reliance on cataplerosis through the mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) pathway to support anabolic functions, such as the production of extracellular matrix. In vivo, lactate maintains/induces populations of postnatal neuronal progenitors/NSCs in a PEPCK-M-dependent manner. Taken together, our data demonstrate that, lactate alone or together with other physical/biochemical cues maintain NSCs/progenitors with a metabolic signature that is classically found in tissues with high anabolic capacity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Famine versus feast: understanding the metabolism of tumors in vivo.

Science.gov (United States)

Mayers, Jared R; Vander Heiden, Matthew G

2015-03-01

To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aspects involved in the (patho)physiology of the metabolic syndrome

NARCIS (Netherlands)

Duivenvoorden, Ilse

2006-01-01

The metabolic syndrome is an increasing problem in our Western society. Many of the features of the metabolic syndrome, like obesity, insulin resistance, dyslipidemia, and hepatic steatosis are established risk factors for cardiovascular disease. Growing evidence supports the important role of body

Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

Science.gov (United States)

De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

2018-01-01

The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

Bosonization relations as bag boundary conditions

International Nuclear Information System (INIS)

Nadkarni, S.; Nielsen, H.B.; Zahed, I.

1984-10-01

The more sophisticated bag models of hadrons become, the less precisely they seem to determine the bag radius. Idealizing this situation leads to the concept of exact bag models - ''Cheshire Cat'' models, CCM'S - where the physics is completely insensitive to changes in the bag radius. CCM's are constructed explitly in 1+1-dimensions, where exact bosonization relations are known. In the formalism of bag models, these relations appear as boundary conditions which ensure that the shifting of the bag wall has no physical effect. Other notable features of 1+1-dimensional CCM's are: (i) Fermion number, though classically confined, can escape the bag via a vector current anomaly at the surface. (ii) Essentially the same boundary action works for a variety of models and its symmetries determine those of the external boson fields. Remarkably enough, this 1+1-dimensional boundary action has precisely the same form as the one used in 3+1-dimensional chiral bag models, lending support to the belief that the latter are indeed approximateCCM's. These 1+1-dimensional results are expected to provide useful guidelines in the attempt to, at least approximately, besonize 3+1-dimensional QCD. (orig.)

Epigenetics and a new look on metabolic syndrome

Czech Academy of Sciences Publication Activity Database

Kuneš, Jaroslav; Vaněčková, I.; Mikulášková, Barbora; Behuliak, M.; Maletínská, Lenka; Zicha, J.

2015-01-01

Roč. 64, č. 5 (2015), s. 611-620 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : metabolic syndrome * epigenetic s * transgenerational inheritance * gene-environmental interactions * obesity * hypertension Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.643, year: 2015 http://www.biomed.cas.cz/physiolres/pdf/64/64_611.pdf

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

Science.gov (United States)

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

2016-01-01

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

OpenAIRE

Ward, Patrick S.; Thompson, Craig B.

2012-01-01

Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria, but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-ass...

Contribution of family social support to the metabolic control of people with diabetes mellitus: A randomized controlled clinical trial.

Science.gov (United States)

Gomes, Lilian Cristiane; Coelho, Anna Claudia Martins; Gomides, Danielle Dos Santos; Foss-Freitas, Maria Cristina; Foss, Milton César; Pace, Ana Emilia

2017-08-01

This randomized controlled clinical trial aimed to evaluate the contribution of family social support to the clinical/metabolic control of people with type 2 diabetes mellitus. Diabetes mellitus is a chronic disease that requires continuous care in order for individuals to reach glycemic control, the primordial goal of treatment. Family social support is essential to the development of care skills and their maintenance. However, there are few studies that investigate the contribution of family social support to diabetes control. The study was developed between June 2011 and May 2013, and included 164 people who were randomized using simple randomization. The intervention group differed from the control group in that it included a family caregiver, who was recognized by the patient as a source of social support. The educational interventions received by people with diabetes mellitus were used as the basis of the education provided through telephone calls to patients' family members and caregivers, and their purpose was to encourage dialogue between the patients and their relatives about the topics related to diabetes. Regarding the clinical impact, the results showed that there was a greater reduction in blood pressure and glycated hemoglobin in the intervention group than in the control group, showing a positive effect on the control of the disease. Families should be incorporated into the care of people with diabetes mellitus and especially in health care programs, in particular those that can promote different forms of social support to strengthen the bond between family members. Copyright © 2017 Elsevier Inc. All rights reserved.

SCREENING OF PLANT EXTRACTS FOR ANTIMICROBIAL ACTIVITY AGAINST BACTERIA

Directory of Open Access Journals (Sweden)

Alexander Vatľák

2014-02-01

Full Text Available The aim of this study was antimicrobial action of the methanolic extracts of Equisetum arvense L. and Urtica dioica L. against gramnegative and grampositive bacteria. The antimicrobial activities of the extracts against gramnegative bacteria: Escherichia coli CCM 3988, Listeria ivanovii CCM 5884, Listeria innocua CCM 4030, Pseudomonas aeruginosa CCM 1960, Serratia rubidaea CCM 4684 and grampositive bacteria: Brochothrix thermosphacta CCM 4769, Enterococcus raffinosus CCM 4216, Lactobacillus rhamnosus CCM 1828, Paenobacillus larvae CCM 4483 and Staphylococcus epidermis CCM 4418 were determined by the disc diffusion method and the microbroth dilution method according to CLSI. Probit analysis was used in this experiment. Of the 2 plant extracts tested, all extracts showed antimicrobial activity against one or more species of microorganisms. The most antimicrobial activity showed methanolic plant extract of E. arvense against S. epidermis with disc diffusion method and with microbroth dilution method against S. rubidaea and plant extract Urtica dioica with disc diffusion method against P. aeruginosa and with microbroth dilution method against S. rubidaea and E. coli.

Calcium metabolism in birds.

Science.gov (United States)

de Matos, Ricardo

2008-01-01

Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

Metabolic reprogramming: a cancer hallmark even warburg did not anticipate.

Science.gov (United States)

Ward, Patrick S; Thompson, Craig B

2012-03-20

Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-associated alterations in metabolism be viewed as an indirect response to cell proliferation and survival signals. We contend that altered metabolism has attained the status of a core hallmark of cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Energy Metabolism Impairment in Migraine.

Science.gov (United States)

Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

2018-06-22

Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Kinetics, bioavailability, and metabolism of RRR-alpha-tocopherol in humans supports lower requirement for vitamin E

Science.gov (United States)

Kinetic models enable nutrient needs and kinetic behaviors to be quantified and provide mechanistic insights into metabolism. Therefore, we modeled and quantified the kinetics, bioavailability and metabolism of RRR-alpha-tocopherol in 12 healthy adults. Six men and six women, aged 27 ± 6 y, each i...

Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner.

Directory of Open Access Journals (Sweden)

Dagmar Srutkova

Full Text Available Reduced microbial diversity has been associated with inflammatory bowel disease (IBD and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis.Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952 and CCDM 372 (Bl 372 were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS-induced colitis was used to compare their beneficial effects in vivo.The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum.We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

Metabolic changes in malnutrition.

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Emery, P W

2005-10-01

This paper is concerned with malnutrition caused by inadequate intake of all the major nutrients rather than deficiency diseases relating to a single micronutrient. Three common situations are recognised: young children in third world countries with protein-energy malnutrition; adults in the same countries who are chronically adapted to subsisting on marginally inadequate diets; and patients who become malnourished as a result of chronic diseases. In all these situations infectious diseases are often also present, and this complicates the interpretation of biochemical and physiological observations. The metabolic response to starvation is primarily concerned with maintaining a supply of water-soluble substrates to supply energy to the brain. Thus there is an initial rise in metabolic rate, reflecting gluconeogenic activity. As fasting progresses, gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones become the main fuel for the brain. With chronic underfeeding the basal metabolic rate per cell appears to fall, but the mechanistic basis for this is not clear. The main adaptation to chronic energy deficiency is slow growth and low adult body size, although the reduction in energy requirement achieved by this is partially offset by the preservation of the more metabolically active organs at the expense of muscle, which has a lower metabolic rate. The interaction between malnutrition and the metabolic response to trauma has been studied using an animal model. The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly attenuated in malnourished rats, suggesting that malnutrition impairs the ability of the body to mobilise substrates to support inflammatory and reparative processes. However, the healing process in wounded muscle remained unimpaired in malnutrition, suggesting that this process has a high biological priority.

Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma.

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Tech, Katherine; Deshmukh, Mohanish; Gershon, Timothy R

2015-01-28

Recent studies show that metabolic patterns typical of cancer cells, including aerobic glycolysis and increased lipogenesis, are not unique to malignancy, but rather originate in physiologic development. In the postnatal brain, where sufficient oxygen for energy metabolism is scrupulously maintained, neural progenitors nevertheless metabolize glucose to lactate and prioritize lipid synthesis over fatty acid oxidation. Medulloblastoma, a cancer of neural progenitors that is the most common malignant brain tumor in children, recapitulates the metabolic phenotype of brain progenitor cells. During the physiologic proliferation of neural progenitors, metabolic enzymes generally associated with malignancy, including Hexokinase 2 (Hk2) and Pyruvate kinase M2 (PkM2) configure energy metabolism to support growth. In these non-malignant cells, expression of Hk2 and PkM2 is driven by transcriptional regulators that are typically identified as oncogenes, including N-myc. Importantly, N-myc continues to drive Hk2 and PkM2 in medulloblastoma. Similarly E2F transcription factors and PPARγ function in both progenitors and medulloblastoma to optimize energy metabolism to support proliferation. These findings show that the "metabolic transformation" that is a hallmark of cancer is not specifically limited to cancer. Rather, metabolic transformation represents a co-opting of developmental programs integral to physiologic growth. Despite their physiologic origins, the molecular mechanisms that mediate metabolic transformation may nevertheless present ideal targets for novel anti-tumor therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Nutrition and the science of disease prevention: a systems approach to support metabolic health

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Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

2017-01-01

Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

Child contact management in high tuberculosis burden countries: A mixed-methods systematic review

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Du Plessis, Lienki; Du Preez, Karen; Carr, Catherine; Mandalakas, Anna M.

2017-01-01

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996–2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (studied and compared in HBCs, and d) outcomes: monitoring and evaluation of CCM outcomes reported in the literature for each CCM cascade step. We included any quantitative, qualitative, mixed-methods study design except for randomized-controlled trials, editorials or commentaries. Thirty-seven studies were reviewed. Child contact losses varied greatly for screening, isoniazid preventive therapy initiation, and completion. CCM challenges included: infrastructure, knowledge, attitudes, stigma, access, competing priorities, and treatment. CCM recommendations included: health system strengthening, health education, and improved preventive therapy. Identified predictors included: index case and clinic characteristics, perceptions of barriers and risk, costs, and treatment characteristics. CCM lacks standardization resulting in common challenges and losses throughout the CCM cascade. Prioritization of a CCM-friendly healthcare environment with improved CCM processes and tools; health education; and active, evidence-based strategies can decrease barriers. A focused approach toward every aspect of the CCM cascade will likely diminish losses throughout the CCM cascade and ultimately decrease TB

SBOLme: a Repository of SBOL Parts for Metabolic Engineering

KAUST Repository

Kuwahara, Hiroyuki

2017-01-12

The Synthetic Biology Open Language (SBOL) is a community-driven open language to promote standardization in synthetic biology. To support the use of SBOL in metabolic engineering, we developed SBOLme, the first open-access repository of SBOL 2-compliant biochemical parts for a wide range of metabolic engineering applications. The URL of our repository is http://www.cbrc.kaust.edu.sa/sbolme.

Effects of temperature, pH and NaCl content on in vitro putrescine and cadaverine production through the growth of Serratia marcescens CCM 303.

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Bubelová, Zuzana; Buňka, František; Taťáková, Monika; Štajnochová, Kateřina; Purevdorj, Khatantuul; Buňková, Leona

2015-01-01

The aim of this study was to evaluate the combined effect of temperature (10, 20 and 37°C), pH (4, 5, 6, 7 and 8), and NaCl content (0, 1, 3, 4, 5 and 6% w/v) on the growth and putrescine and cadaverine production of Serratia marcescens CCM 303 under model conditions. The decarboxylase activity of S. marcescens was monitored in broth after cultivation. The cultivation medium was enriched with selected amino acids (ornithine, arginine and lysine; 0.2% w/v each) serving as precursors of biogenic amines. Levels of putrescine and cadaverine in broth were analysed by high-performance liquid chromatography after pre-column derivatisation with o-phthalaldehyde reagent. S. marcescens produced higher amounts of putrescine (up to 2096.8 mg L(-1)) compared to cadaverine content (up to 343.3 mg L(-1)) in all cultivation media. The highest putrescine and cadaverine concentrations were reached during cultivation at 10-20°C, pH 5-7 and NaCl content 1-3% w/v. On the other hand, the highest BAs production of individual cell (recalculated based on a cell; so called "yield factor") was observed at 10°C, pH 4 and salt concentration 3-5% w/v as a response to environmental stress.

Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors

OpenAIRE

Montgomery, David C.; Sorum, Alexander W.; Guasch, Laura; Nicklaus, Marc C.; Meier, Jordan L.

2015-01-01

The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the met...

Modelling central metabolic fluxes by constraint-based optimization reveals metabolic reprogramming of developing Solanum lycopersicum (tomato) fruit.

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Colombié, Sophie; Nazaret, Christine; Bénard, Camille; Biais, Benoît; Mengin, Virginie; Solé, Marion; Fouillen, Laëtitia; Dieuaide-Noubhani, Martine; Mazat, Jean-Pierre; Beauvoit, Bertrand; Gibon, Yves

2015-01-01

Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs, including fruits. Guided by our current understanding of heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of co-factors and energy, was constructed in order to describe metabolic shifts that occur through the nine sequential stages of Solanum lycopersicum (tomato) fruit development. The measured concentrations of the main biomass components and the accumulated metabolites in the pericarp, determined at each stage, were fitted in order to calculate, by derivation, the corresponding external fluxes. They were used as constraints to solve the model by minimizing the internal fluxes. The distribution of the calculated fluxes of central metabolism were then analysed and compared with known metabolic behaviours. For instance, the partition of the main metabolic pathways (glycolysis, pentose phosphate pathway, etc.) was relevant throughout fruit development. We also predicted a valid import of carbon and nitrogen by the fruit, as well as a consistent CO2 release. Interestingly, the energetic balance indicates that excess ATP is dissipated just before the onset of ripening, supporting the concept of the climacteric crisis. Finally, the apparent contradiction between calculated fluxes with low values compared with measured enzyme capacities suggest a complex reprogramming of the metabolic machinery during fruit development. With a powerful set of experimental data and an accurate definition of the metabolic system, this work provides important insight into the metabolic and physiological requirements of the developing tomato fruits. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

Metabolism and virulence in Neisseria meningitidis

Directory of Open Access Journals (Sweden)

Christoph eSchoen

2014-08-01

Full Text Available A longstanding question in infection biology addresses the genetic basis for invasive behaviour in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

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Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

2014-08-01

There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Flux Balance Analysis of Cyanobacterial Metabolism.The Metabolic Network of Synechocystis sp. PCC 6803

Czech Academy of Sciences Publication Activity Database

Knoop, H.; Gründel, M.; Zilliges, Y.; Lehmann, R.; Hoffmann, S.; Lockau, W.; Steuer, Ralf

2013-01-01

Roč. 9, č. 6 (2013), e1003081-e1003081 ISSN 1553-7358 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : SP STRAIN PCC-6803 * SP ATCC 51142 * photoautotrophic metabolism * anacystis-nidulans * reconstructions * pathway * plants * models * growth Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.829, year: 2013

[Difficulties and concerns identified by Puerto Rican youth with insulin-dependent diabetes mellitus (IDDM): their relationship with metabolic control, hopelessness, social support, and depressive symptoms].

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Rosselló, Jeannette; Maysonet Guzmán, Marielisa

2006-12-01

Insulin-dependent diabetes mellitus (IDDM) is a chronic health condition that affects 18 of every 100,000 Puerto Rican youth. Few research studies have been performed on the problems that youth with diabetes encounter and how they are related to adherence to treatment and adequate metabolic control. Adequate metabolic control is associated with fewer short and long-term medical complications, as well as better quality of life. Adapting to the demands and stressors associated with IDDM and its treatment is a task that can prove to be difficult for youth with diabetes due to having to make adjustments, alterations, and following a prescribed regimen in their daily activities. The main purpose of this investigation was to explore difficulties and worries identified by Puerto Rican youth with IDDM. This study examined whether there is a relationship between difficulties and worries, and adequate metabolic control, hopelessness, social support and depressive symptomatology. One hundred and one youth with IDDM between the ages of 8 and 17 (45 male, 56 female) were evaluated. Analysis of frequencies, correlations, and comparison tests were performed by group (gender, age, diabetes duration, and metabolic control. Results reveal that some of the difficulties identified by Puerto Rican youth with IDDM were: not eating candy and/or cake, self-monitoring blood glucose at school, doing things on time, and waking up early. Among the worries they reported were: insulin reactions and thinking that they might have to go to the hospital.

Continuous esterification to produce biodiesel by SPES/PES/NWF composite catalytic membrane in flow-through membrane reactor: experimental and kinetic studies.

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Shi, Wenying; He, Benqiao; Cao, Yuping; Li, Jianxin; Yan, Feng; Cui, Zhenyu; Zou, Zhiqun; Guo, Shiwei; Qian, Xiaomin

2013-02-01

A novel composite catalytic membrane (CCM) was prepared from sulfonated polyethersulfone (SPES) and polyethersulfone (PES) blend supported by non-woven fabrics, as a heterogeneous catalyst to produce biodiesel from continuous esterification of oleic acid with methanol in a flow-through mode. A kinetic model of esterification was established based on a plug-flow assumption. The effects of the CCM structure (thickness, area, porosity, etc.), reaction temperature and the external and internal mass transfer resistances on esterification were investigated. The results showed that the CCM structure had a significant effect on the acid conversion. The external mass transfer resistance could be neglected when the flow rate was over 1.2 ml min(-1). The internal mass transfer resistance impacted on the conversion when membrane thickness was over 1.779 mm. An oleic acid conversion kept over 98.0% for 500 h of continuous running. The conversions obtained from the model are in good agreement with the experimental data. Copyright © 2012 Elsevier Ltd. All rights reserved.

Constraining Genome-Scale Models to Represent the Bow Tie Structure of Metabolism for 13C Metabolic Flux Analysis

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Tyler W. H. Backman

2018-01-01

Full Text Available Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13 C Metabolic Flux Analysis ( 13 C MFA and Two-Scale 13 C Metabolic Flux Analysis (2S- 13 C MFA are two techniques used to determine such fluxes. Both operate on the simplifying approximation that metabolic flux from peripheral metabolism into central “core” carbon metabolism is minimal, and can be omitted when modeling isotopic labeling in core metabolism. The validity of this “two-scale” or “bow tie” approximation is supported both by the ability to accurately model experimental isotopic labeling data, and by experimentally verified metabolic engineering predictions using these methods. However, the boundaries of core metabolism that satisfy this approximation can vary across species, and across cell culture conditions. Here, we present a set of algorithms that (1 systematically calculate flux bounds for any specified “core” of a genome-scale model so as to satisfy the bow tie approximation and (2 automatically identify an updated set of core reactions that can satisfy this approximation more efficiently. First, we leverage linear programming to simultaneously identify the lowest fluxes from peripheral metabolism into core metabolism compatible with the observed growth rate and extracellular metabolite exchange fluxes. Second, we use Simulated Annealing to identify an updated set of core reactions that allow for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13 C MFA or 2S- 13 C MFA, as well as provide for a substantially lower set of flux bounds for fluxes into the core as compared with previous methods. We provide an open source Python implementation of these algorithms at https://github.com/JBEI/limitfluxtocore.

Vascular permeability in cerebral cavernous malformations

DEFF Research Database (Denmark)

Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao

2015-01-01

Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observ...

An Integrative Approach to Energy Carbon and Redox Metabolism In Cyanobacterium Synechocystis

Energy Technology Data Exchange (ETDEWEB)

Dr. Ross Overbeek

2003-06-30

The main objectives for the first year were to produce a detailed metabolic reconstruction of synechocystis sp.pcc6803 especially in interrelated arrears of photosynthesis respiration and central carbon metabolism to support a more complete understanding and modeling of this organism. Additionally, IG, Inc. provided detailed bioinformatic analysis of selected functional systems related to carbon and energy generation and utilization, and of the corresponding pathways functional roles and individual genes to support wet lab experiments by collaborators.

Sleep and metabolic function.

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Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

2012-01-01

Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

The Hunger Games: p53 regulates metabolism upon serine starvation.

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Tavana, Omid; Gu, Wei

2013-02-05

Cancer cells reprogram their metabolism to support a high proliferative rate. A new study shows that, upon serine starvation, the tumor suppressor p53 activates p21 to shift metabolic flux from purine biosynthesis to glutathione production, which enhances cellular proliferation and viability by combating ROS (Maddocks et al., 2013). Copyright © 2013 Elsevier Inc. All rights reserved.

Gout and Metabolic Syndrome: a Tangled Web.

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Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

2017-08-26

The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities. Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

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Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

Science.gov (United States)

Karus, Claudia; Ziemens, Daniel; Rose, Christine R

2015-01-01

Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

Science.gov (United States)

Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

2016-05-01

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

International Nuclear Information System (INIS)

Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

2014-01-01

Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin.

Science.gov (United States)

Retta, Saverio Francesco; Glading, Angela J

2016-12-01

Cerebral Cavernous Malformation (CCM) is a vascular disease of proven genetic origin, which may arise sporadically or is inherited as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. CCM lesions exhibit a range of different phenotypes, including wide inter-individual differences in lesion number, size, and susceptibility to intracerebral hemorrhage (ICH). Lesions may remain asymptomatic or result in pathological conditions of various type and severity at any age, with symptoms ranging from recurrent headaches to severe neurological deficits, seizures, and stroke. To date there are no direct therapeutic approaches for CCM disease besides the surgical removal of accessible lesions. Novel pharmacological strategies are particularly needed to limit disease progression and severity and prevent de novo formation of CCM lesions in susceptible individuals. Useful insights into innovative approaches for CCM disease prevention and treatment are emerging from a growing understanding of the biological functions of the three known CCM proteins, CCM1/KRIT1, CCM2 and CCM3/PDCD10. In particular, accumulating evidence indicates that these proteins play major roles in distinct signaling pathways, including those involved in cellular responses to oxidative stress, inflammation and angiogenesis, pointing to pathophysiological mechanisms whereby the function of CCM proteins may be relevant in preventing vascular dysfunctions triggered by these events. Indeed, emerging findings demonstrate that the pleiotropic roles of CCM proteins reflect their critical capacity to modulate the fine-tuned crosstalk between redox signaling and autophagy that govern cell homeostasis and stress responses, providing a novel mechanistic scenario that reconciles both the multiple signaling pathways linked to CCM proteins and the distinct therapeutic approaches proposed so far. In addition, recent studies in CCM patient cohorts suggest that genetic susceptibility

Lipoprotein metabolism indicators improve cardiovascular risk prediction.

Directory of Open Access Journals (Sweden)

Daniël B van Schalkwijk

Full Text Available BACKGROUND: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to investigate whether lipoprotein metabolism indicators can improve cardiovascular risk prediction and therapy management. METHODS AND RESULTS: We calculated lipoprotein metabolism indicators for 1981 subjects (145 cases, 1836 controls from the Framingham Heart Study offspring cohort in which NMR lipoprotein profiles were measured. We applied a statistical learning algorithm using a support vector machine to select conventional risk factors and lipoprotein metabolism indicators that contributed to predicting risk for general cardiovascular disease. Risk prediction was quantified by the change in the Area-Under-the-ROC-Curve (ΔAUC and by risk reclassification (Net Reclassification Improvement (NRI and Integrated Discrimination Improvement (IDI. Two VLDL lipoprotein metabolism indicators (VLDLE and VLDLH improved cardiovascular risk prediction. We added these indicators to a multivariate model with the best performing conventional risk markers. Our method significantly improved both CVD prediction and risk reclassification. CONCLUSIONS: Two calculated VLDL metabolism indicators significantly improved cardiovascular risk prediction. These indicators may help to reduce prescription of unnecessary cholesterol-lowering medication, reducing costs and possible side-effects. For clinical application, further validation is required.

Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content

Science.gov (United States)

Vaughan, Roger A.; Gannon, Nicholas P.; Carriker, Colin R.

2015-01-01

Beetroot (甜菜 tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription–polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID:26870674

Independent Evaluation of the integrated Community Case Management of Childhood Illness Strategy in Malawi Using a National Evaluation Platform Design.

Science.gov (United States)

Amouzou, Agbessi; Kanyuka, Mercy; Hazel, Elizabeth; Heidkamp, Rebecca; Marsh, Andrew; Mleme, Tiope; Munthali, Spy; Park, Lois; Banda, Benjamin; Moulton, Lawrence H; Black, Robert E; Hill, Kenneth; Perin, Jamie; Victora, Cesar G; Bryce, Jennifer

2016-03-01

We evaluated the impact of integrated community case management of childhood illness (iCCM) on careseeking for childhood illness and child mortality in Malawi, using a National Evaluation Platform dose-response design with 27 districts as units of analysis. "Dose" variables included density of iCCM providers, drug availability, and supervision, measured through a cross-sectional cellular telephone survey of all iCCM-trained providers. "Response" variables were changes between 2010 and 2014 in careseeking and mortality in children aged 2-59 months, measured through household surveys. iCCM implementation strength was not associated with changes in careseeking or mortality. There were fewer than one iCCM-ready provider per 1,000 under-five children per district. About 70% of sick children were taken outside the home for care in both 2010 and 2014. Careseeking from iCCM providers increased over time from about 2% to 10%; careseeking from other providers fell by a similar amount. Likely contributors to the failure to find impact include low density of iCCM providers, geographic targeting of iCCM to "hard-to-reach" areas although women did not identify distance from a provider as a barrier to health care, and displacement of facility careseeking by iCCM careseeking. This suggests that targeting iCCM solely based on geographic barriers may need to be reconsidered. © The American Society of Tropical Medicine and Hygiene.

Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

DEFF Research Database (Denmark)

Graham, Terry E; Battram, Danielle S; Dela, Flemming

2008-01-01

and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically...... important. The few studies examining human muscle metabolism directly have also supported the fact that there is no change in fat or carbohydrate metabolism, but these usually have had a small sample size. We combined the data from muscle biopsy analyses of several similar studies to generate a sample size...

Insights into Brain Glycogen Metabolism

Science.gov (United States)

Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-01-01

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

Sensitivity of temporal heart rate variability in Poincaré plot to changes in parasympathetic nervous system activity.

Science.gov (United States)

Karmakar, Chandan K; Khandoker, Ahsan H; Voss, Andreas; Palaniswami, Marimuthu

2011-03-03

A novel descriptor (Complex Correlation Measure (CCM)) for measuring the variability in the temporal structure of Poincaré plot has been developed to characterize or distinguish between Poincaré plots with similar shapes. This study was designed to assess the changes in temporal structure of the Poincaré plot using CCM during atropine infusion, 70° head-up tilt and scopolamine administration in healthy human subjects. CCM quantifies the point-to-point variation of the signal rather than gross description of the Poincaré plot. The physiological relevance of CCM was demonstrated by comparing the changes in CCM values with autonomic perturbation during all phases of the experiment. The sensitivities of short term variability (SD1), long term variability (SD2) and variability in temporal structure (CCM) were analyzed by changing the temporal structure by shuffling the sequences of points of the Poincaré plot. Surrogate analysis was used to show CCM as a measure of changes in temporal structure rather than random noise and sensitivity of CCM with changes in parasympathetic activity. CCM was found to be most sensitive to changes in temporal structure of the Poincaré plot as compared to SD1 and SD2. The values of all descriptors decreased with decrease in parasympathetic activity during atropine infusion and 70° head-up tilt phase. In contrast, values of all descriptors increased with increase in parasympathetic activity during scopolamine administration. The concordant reduction and enhancement in CCM values with parasympathetic activity indicates that the temporal variability of Poincaré plot is modulated by the parasympathetic activity which correlates with changes in CCM values. CCM is more sensitive than SD1 and SD2 to changes of parasympathetic activity.

The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

Science.gov (United States)

Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

2018-03-15

Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

Metabolic syndrome in hyperprolactinemia

DEFF Research Database (Denmark)

Andersen, Marianne; Glintborg, Dorte

2018-01-01

The metabolic syndrome (MetS) is a conglomerate of clinical findings that convey into increased morbidity and mortality from type 2 diabetes mellitus (T2D) and cardiovascular disease. Hyperprolactinemia (hyperPRL) is associated with components of MetS, especially during pregnancy. Endogenous levels...... in patients with T2D. HyperPRL is a biomarker for decreased dopaminergic tonus in the hypothalamic-pituitary circuit. Patients with a prolactinoma, patients with schizophrenia and/or T2D often have disturbances in this balance and the finding of lower prolactin (PRL) levels in polycystic ovary syndrome (PCOS......) may indicate increased dopaminergic tonus. Recent studies supported that PRL levels within or above reference range may be differently related to MetS. In healthy study populations and in PCOS, PRL levels were inversely associated with metabolic risk markers. Ongoing research on PRL fragments...

[Development and application of component-based Chinese medicine theory].

Science.gov (United States)

Zhang, Jun-Hua; Fan, Guan-Wei; Zhang, Han; Fan, Xiao-Hui; Wang, Yi; Liu, Li-Mei; Li, Chuan; Gao, Yue; Gao, Xiu-Mei; Zhang, Bo-Li

2017-11-01

Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a

Metabolic rates of giant pandas inform conservation strategies

Science.gov (United States)

Fei, Yuxiang; Hou, Rong; Spotila, James R.; Paladino, Frank V.; Qi, Dunwu; Zhang, Zhihe

2016-06-01

The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction.

Dynamic metabolism modelling of urban water services--demonstrating effectiveness as a decision-support tool for Oslo, Norway.

Science.gov (United States)

Venkatesh, G; Sægrov, Sveinung; Brattebø, Helge

2014-09-15

Urban water services are challenged from many perspectives and different stakeholders demand performance improvements along economic, social and environmental dimensions of sustainability. In response, urban water utilities systematically give more attention to criteria such as water safety, climate change adaptation and mitigation, environmental life cycle assessment (LCA), total cost efficiency, and on how to improve their operations within the water-energy-carbon nexus. The authors of this paper collaborated in the development of a 'Dynamic Metabolism Model' (DMM). The model is developed for generic use in the sustainability assessment of urban water services, and it has been initially tested for the city of Oslo, Norway. The purpose has been to adopt a holistic systemic perspective to the analysis of metabolism and environmental impacts of resource flows in urban water and wastewater systems, in order to offer a tool for the examination of future strategies and intervention options in such systems. This paper describes the model and its application to the city of Oslo for the analysis time period 2013-2040. The external factors impacting decision-making and interventions are introduced along with realistic scenarios developed for the testing, after consultation with officials at the Oslo Water and Wastewater Works (Norway). Possible interventions that the utility intends to set in motion are defined and numerically interpreted for incorporation into the model, and changes in the indicator values over the time period are determined. This paper aims to demonstrate the effectiveness and usefulness of the DMM, as a decision-support tool for water-wastewater utilities. The scenarios considered and interventions identified do not include all possible scenarios and interventions that can be relevant for water-wastewater utilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical Decision Support to Implement CYP2D6 Drug-Gene Interaction.

Science.gov (United States)

Caraballo, Pedro J; Parkulo, Mark; Blair, David; Elliott, Michelle; Schultz, Cloann; Sutton, Joseph; Rao, Padma; Bruflat, Jamie; Bleimeyer, Robert; Crooks, John; Gabrielson, Donald; Nicholson, Wayne; Rohrer Vitek, Carolyn; Wix, Kelly; Bielinski, Suzette J; Pathak, Jyotishman; Kullo, Iftikhar

2015-01-01

The level of CYP2D6 metabolic activity can be predicted by pharmacogenomic testing, and concomitant use of clinical decision support has the potential to prevent adverse effects from those drugs metabolized by this enzyme. Our initial findings after implementation of clinical decision support alerts integrated in the electronic health records suggest high feasibility, but also identify important challenges.

The Comparative Studies of Binding Activity of Curcumin and Didemethylated Curcumin with Selenite: Hydrogen Bonding vs Acid-Base Interactions

Science.gov (United States)

Liao, Jiahn-Haur; Wu, Tzu-Hua; Chen, Ming-Yi; Chen, Wei-Ting; Lu, Shou-Yun; Wang, Yi-Hsuan; Wang, Shao-Pin; Hsu, Yen-Min; Huang, Yi-Shiang; Huang, Zih-You; Lin, Yu-Ching; Chang, Ching-Ming; Huang, Fu-Yung; Wu, Shih-Hsiung

2015-12-01

In this report, the in vitro relative capabilities of curcumin (CCM) and didemethylated curcumin (DCCM) in preventing the selenite-induced crystallin aggregation were investigated by turbidity tests and isothermal titration calorimetry (ITC). DCCM showed better activity than CCM. The conformers of CCM/SeO32- and DCCM/SeO32- complexes were optimized by molecular orbital calculations. Results reveal that the selenite anion surrounded by CCM through the H-bonding between CCM and selenite, which is also observed via IR and NMR studied. For DCCM, the primary driving force is the formation of an acid-base adduct with selenite showing that the phenolic OH group of DCCM was responsible for forming major conformer of DCCM. The formation mechanisms of selenite complexes with CCM or DCCM explain why DCCM has greater activity than CCM in extenuating the toxicity of selenite as to prevent selenite-induced lens protein aggregation.

A Metabolic Race

Directory of Open Access Journals (Sweden)

A.M.S. Costa et al.

2017-07-01

Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

THE REDOX PATHWAY OF Pseudomonas aeruginosa CYTOCHROME C BIOGENESIS

Directory of Open Access Journals (Sweden)

Eva Di Silvio

2012-06-01

Full Text Available Cytochrome c contains heme covalently bound to the polypeptide chain through two thioether bonds between the heme vinyl groups and the two cysteines of the conserved heme- binding motif of the apoprotein. Surprisingly, the biochemical events leading to the synthesis of the functional holoprotein in the cell are largely unknown. In the human pathogen Pseudomonas aeruginosa, the biogenesis of Cytc is mediated by a group of membrane or membrane-anchored proteins (CcmABCDEFGHI, exposing their active site to the periplasm. The Ccm proteins involved in the necessary reduction of apoCyt disulfide bond are CcmG and CcmH. Here we present the structural and functional characterization of these two redox-active proteins. We determined the crystal structure of CcmG, both in the oxidized and the reduced state. CcmG is a membrane-anchored thioredoxinlike protein acting as a mild reductant in the redox pathway of Cytc biogenesis. The 3D structure of the soluble periplasmic domain of CcmH revealed that it adopts a peculiar three-helix bundle fold that is different from that of canonical thiol-oxidoreductases. Moreover, we present protein-protein interaction experiments aiming at elucidating the molecular mechanism of the reduction of apoCyt disulfide bond for heme attachment in vivo. On the basis of the structural and functional data on CcmG, CcmH and their interactions, we propose an assembly line for Cytc biogenesis in P. aeruginosa in which reduced CcmH specifically recognizes, binds and reduces oxidized apoCyt via the formation of a mixed disulfide complex, which is subsequently resolved by CcmG.

Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

Science.gov (United States)

Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

2014-10-01

Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. © 2014 American Society of Plant Biologists. All rights reserved.

Metabolic costs of hybridization in newts

Czech Academy of Sciences Publication Activity Database

Gvoždík, Lumír

2012-01-01

Roč. 61, 3-4 (2012), s. 197-201 ISSN 0139-7893 R&D Projects: GA ČR GAP506/10/2170; GA MŠk LC06073 Institutional support: RVO:68081766 Keywords : oxygen consumption * energetic metabolism * hybrids * Triturus * amphibians * mitonuclear interactions * reproductive barriers Subject RIV: EG - Zoology Impact factor: 0.494, year: 2012

Melatonin, mitochondria, and the metabolic syndrome.

Science.gov (United States)

Cardinali, Daniel P; Vigo, Daniel E

2017-11-01

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

Curcumin-incorporated albumin nanoparticles and its tumor image

International Nuclear Information System (INIS)

Gong, Guangming; Wu, Rongchun; Pan, Qinqin; Wang, Kaikai; Sun, Yong; Lu, Ying

2015-01-01

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)–curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA–CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA–CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA–CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes. (paper)

Curcumin-incorporated albumin nanoparticles and its tumor image

Science.gov (United States)

Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

2015-01-01

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

Curcumin-incorporated albumin nanoparticles and its tumor image.

Science.gov (United States)

Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

2015-01-30

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

Pressurized Martian-Like Pure CO2 Atmosphere Supports Strong Growth of Cyanobacteria, and Causes Significant Changes in their Metabolism

Science.gov (United States)

Murukesan, Gayathri; Leino, Hannu; Mäenpää, Pirkko; Ståhle, Kurt; Raksajit, Wuttinun; Lehto, Harry J.; Allahverdiyeva-Rinne, Yagut; Lehto, Kirsi

2016-03-01

Surviving of crews during future missions to Mars will depend on reliable and adequate supplies of essential life support materials, i.e. oxygen, food, clean water, and fuel. The most economical and sustainable (and in long term, the only viable) way to provide these supplies on Martian bases is via bio-regenerative systems, by using local resources to drive oxygenic photosynthesis. Selected cyanobacteria, grown in adequately protective containment could serve as pioneer species to produce life sustaining substrates for higher organisms. The very high (95.3 %) CO2 content in Martian atmosphere would provide an abundant carbon source for photo-assimilation, but nitrogen would be a strongly limiting substrate for bio-assimilation in this environment, and would need to be supplemented by nitrogen fertilizing. The very high supply of carbon, with rate-limiting supply of nitrogen strongly affects the growth and the metabolic pathways of the photosynthetic organisms. Here we show that modified, Martian-like atmospheric composition (nearly 100 % CO2) under various low pressure conditions (starting from 50 mbar to maintain liquid water, up to 200 mbars) supports strong cellular growth. Under high CO2 / low N2 ratio the filamentous cyanobacteria produce significant amount of H2 during light due to differentiation of high amount of heterocysts.

Redesign of the Human Metabolic Simulator

Science.gov (United States)

Duffield, Bruce; Jeng, Frank; Lange, Kevin

2004-01-01

The National Aeronautics and Space Administration (NASA) is currently building a Human Metabolic Simulator (HMS) at the Johnson Space Center as part of the Advanced Life Support Air Revitalization Technology Evaluation Facility (ARTEF). The purpose of ARTEF is to evaluate Environmental Control and Life Support System Technologies for Advanced Missions. The HMS is needed to reproduce the primary metabolic effects of human respiration on an enclosed atmosphere when humans cannot be present and the impact of human presence on the system is required. A HMS was designed, built and successfully operated in 2000 but larger crew size requirements and the expense of upgrade of the current system necessitate redesign. This paper addresses the redesign. Several concepts were considered, ranging from chemical oxidation of a hydrocarbon like ethanol or ethyl acetate to carbon dioxide and water, oxidation of an iron-containing compound, or by using a fuel cell. For reasons of cost, simplicity, safety and other factors, the concept chosen includes: a molecular sieve packaged as an industrial oxygen concentrator to remove oxygen from the atmosphere, with direct carbon dioxide, water and heat injection. The water injection is done via heating water to steam with a heat exchanger and thermal effects are handled by directly adding heat to the air stream with a second heat exchanger. Both heat exchangers are supplied by a hot oil loop. The amount of oxygen removal, carbon dioxide addition, water addition and heat addition were calculated using metabolic profiles for respiration and heat, calculated using a series of empirical equations developed for International Space Station (ISS). Sketches of the Human Metabolic Simulator and the hot oil bath loop used to supply heat to the heat exchangers are included

Metabolic assessments during extra-vehicular activity

Science.gov (United States)

Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

Directory of Open Access Journals (Sweden)

Michelle E. Watts

2018-06-01

Full Text Available Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

Metabolic rates of giant pandas inform conservation strategies

Science.gov (United States)

Fei, Yuxiang; Hou, Rong; Spotila, James R.; Paladino, Frank V.; Qi, Dunwu; Zhang, Zhihe

2016-01-01

The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction. PMID:27264109

A Synthetic Alternative to Canonical One-Carbon Metabolism.

Science.gov (United States)

Bouzon, Madeleine; Perret, Alain; Loreau, Olivier; Delmas, Valérie; Perchat, Nadia; Weissenbach, Jean; Taran, Frédéric; Marlière, Philippe

2017-08-18

One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO 2 . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.

Immunoreactive proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 identified by gnotobiotic mono-colonized mice sera, immune rabbit sera and nonimmune human sera.

Directory of Open Access Journals (Sweden)

Sabina Górska

2016-09-01

Full Text Available The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952 and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372.

Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

DEFF Research Database (Denmark)

Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

2015-01-01

Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders.

Science.gov (United States)

MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J

2016-01-01

Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection.

Food for thought: Impact of metabolism on neuronal excitability.

Science.gov (United States)

Katsu-Jiménez, Yurika; Alves, Renato M P; Giménez-Cassina, Alfredo

2017-11-01

Neuronal excitability is a highly demanding process that requires high amounts of energy and needs to be exquisitely regulated. For this reason, brain cells display active energy metabolism to support their activity. Independently of their roles as energy substrates, compelling evidence shows that the nature of the fuels that neurons use contribute to fine-tune neuronal excitability. Crosstalk of neurons with glial populations also plays a prominent role in shaping metabolic flow in the brain. In this review, we provide an overview on how different carbon substrates and metabolic pathways impact neurotransmission, and the potential implications for neurological disorders in which neuronal excitability is deregulated, such as epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

Science.gov (United States)

Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

2013-01-01

Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc; Magistretti, Pierre J.; Allaman, Igor

2013-01-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

KAUST Repository

Martin, Jean Luc

2013-09-01

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

Deranged Cardiac Metabolism and the Pathogenesis of Heart Failure

Science.gov (United States)

2016-01-01

Activation of the neuro-hormonal system is a pathophysiological consequence of heart failure. Neuro-hormonal activation promotes metabolic changes, such as insulin resistance, and determines an increased use of non-carbohydrate substrates for energy production. Fasting blood ketone bodies as well as fat oxidation are increased in patients with heart failure, yielding a state of metabolic inefficiency. The net result is additional depletion of myocardial adenosine triphosphate, phosphocreatine and creatine kinase levels with further decreased efficiency of mechanical work. In this context, manipulation of cardiac energy metabolism by modification of substrate use by the failing heart has produced positive clinical results. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. The additional use of drugs able to partially inhibit fatty acids oxidation in patients with heart failure may therefore yield a significant protective effect for clinical symptoms and cardiac function improvement, and simultaneously ameliorate left ventricular remodelling. Certainly, to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicentre, randomised controlled trial should be performed. PMID:28785448

Two-faced property of a market factor in asset pricing and diversification effect

Science.gov (United States)

Eom, Cheoljun

2017-04-01

This study empirically investigates the test hypothesis that a market factor acting as a representative common factor in the pricing models has a negative influence on constructing a well-diversified portfolio from the Markowitz mean-variance optimization function (MVOF). We use the comparative correlation matrix (C-CM) method to control a single eigenvalue among all eigenvalues included in the sample correlation matrix (S-CM), through the random matrix theory (RMT). In particular, this study observes the effect of the largest eigenvalue that has the property of the market factor. According to the results, the largest eigenvalue has the highest explanatory power on the stock return changes. The C-CM without the largest eigenvalue in the S-CM constructs a more diversified portfolio capable of improving the practical applicability of the MVOF. Moreover, the more diversified portfolio constructed from this C-CM has better out-of-sample performance in the future period. These results support the test hypothesis for the two-faced property of the market factor, defined by the largest eigenvalue.

Elucidating the adaptation and temporal coordination of metabolic pathways using in-silico evolution

Czech Academy of Sciences Publication Activity Database

Gottstein, W.; Müller, Stefan; Herzel, H.; Steuer, Ralf

2014-01-01

Roč. 117, mar (2014), s. 68-76 ISSN 0303-2647 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : evolutionary algorithms * flux- balance analysis * metabolic oscillations * metabolism * systems biology Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.548, year: 2014

Metabolic syndrome in patients with ischemic heart disease

International Nuclear Information System (INIS)

Yasmin, S.; Naveed, T.; Shakoor, T.

2008-01-01

To determine the frequency of metabolic syndrome in patients with Ischemic Heart Disease (IHD). Cross-sectional, descriptive study. A total of 100 subjects with ischemic heart disease, fulfilling the inclusion criteria, were enrolled in the study. Demographic data (age and gender) and the 5 component conditions of the metabolic syndrome were noted. Subjects were physically assessed for the abdominal obesity, based on waist circumference. Fasting blood samples for glucose and lipid profile in first 24 hours after acute coronary insult were drawn and tested in central laboratory. Variables were processed for descriptive statistics. In this study population, 68% were male and 32% were female with mean age of 52 +-13.6 years in men and 56 +- 12.5 years in women. Frequency of metabolic syndrome was 32% in men and 28% in women. It increased with age. The highest rate of metabolic syndrome was in men diagnosed as STEMI (odds ratio: 3.39, 95% CI=1.36-8.41). Frequency of metabolic syndrome was high among the patients with IHD. It supports the potential for preventive efforts in persons with high-risk of IHD. (author)

Mitochondrial DNA variation, but not nuclear DNA, sharply divides morphologically identical chameleons along an ancient geographic barrier.

Directory of Open Access Journals (Sweden)

Dan Bar Yaacov

Full Text Available The Levant is an important migration bridge, harboring border-zones between Afrotropical and palearctic species. Accordingly, Chameleo chameleon, a common species throughout the Mediterranean basin, is morphologically divided in the southern Levant (Israel into two subspecies, Chamaeleo chamaeleon recticrista (CCR and C. c. musae (CCM. CCR mostly inhabits the Mediterranean climate (northern Israel, while CCM inhabits the sands of the north-western Negev Desert (southern Israel. AFLP analysis of 94 geographically well dispersed specimens indicated moderate genetic differentiation (PhiPT = 0.097, consistent with the classical division into the two subspecies, CCR and CCM. In contrast, sequence analysis of a 637 bp coding mitochondrial DNA (mtDNA fragment revealed two distinct phylogenetic clusters which were not consistent with the morphological division: one mtDNA cluster consisted of CCR specimens collected in regions northern of the Jezreel Valley and another mtDNA cluster harboring specimens pertaining to both the CCR and CCM subspecies but collected southern of the Jezreel Valley. AMOVA indicated clear mtDNA differentiation between specimens collected northern and southern to the Jezreel Valley (PhiPT = 0.79, which was further supported by a very low coalescent-based estimate of effective migration rates. Whole chameleon mtDNA sequencing (∼17,400 bp generated from 11 well dispersed geographic locations revealed 325 mutations sharply differentiating the two mtDNA clusters, suggesting a long allopatric history further supported by BEAST. This separation correlated temporally with the existence of an at least 1 million year old marine barrier at the Jezreel Valley exactly where the mtDNA clusters meet. We discuss possible involvement of gender-dependent life history differences in maintaining such mtDNA genetic differentiation and suggest that it reflects (ancient local adaptation to mitochondrial-related traits.

Implementation of a program for type 2 diabetes based on the Chronic Care Model in a hospital-centered health care system: "the Belgian experience"

Directory of Open Access Journals (Sweden)

Van Royen Paul

2009-08-01

Full Text Available Abstract Background Most research publications on Chronic Care Model (CCM implementation originate from organizations or countries with a well-structured primary health care system. Information about efforts made in countries with a less well-organized primary health care system is scarce. In 2003, the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting, a setting where the organisational framework for chronic care is mainly hospital-centered. Methods Process evaluation of an action research project (2003–2007 guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients. In consultation with the region a program for type 2 diabetes patients was developed. The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey (ACIC. A multimethod approach was used to evaluate the implementation process. The resulting data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process. Results The overall ACIC score improved from 1.45 (limited support at the start of the study to 5.5 (basic support at the end of the study. The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care. The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator. Important barriers were the complexity of the intervention, the lack of quality data, inadequate information technology support, the lack of commitment procedures and the uncertainty about sustainable funding. Conclusion Guided by the CCM, this study highlights the opportunities and the bottlenecks for adapting chronic care

Neuron-glia metabolic coupling and plasticity.

Science.gov (United States)

Magistretti, Pierre J

2006-06-01

The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the 'astrocyte-neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron-glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

"Metabolic staging" after major trauma - a guide for clinical decision making?

Directory of Open Access Journals (Sweden)

Moore Ernest E

2010-06-01

Full Text Available Abstract Metabolic changes after major trauma have a complex underlying pathophysiology. The early posttraumatic stress response is associated with a state of hyperinflammation, with increased oxygen consumption and energy expenditure. This hypercatabolic state must be recognized early and mandates an early nutritional management strategy. A proactive concept of early enteral "immunonutrition" in severely injured patients, is aimed at counterbalancing the negative aspects of hyperinflammation and hypercatabolism in order to reduce the risk of late complications, including infections and posttraumatic organ failure. Recently, the concept of "metabolic staging" has been advocated, which takes into account the distinct inflammatory phases and metabolic phenotypes after major trauma, including the "ischemia/reperfusion phenotype", the "leukocytic phenotype", and the "angiogenic phenotype". The potential clinical impact of metabolic staging, and of an appropriately adapted "metabolic control" and nutritional support, remains to be determined.

Hypothalamic control of energy and glucose metabolism.

Science.gov (United States)

Sisley, Stephanie; Sandoval, Darleen

2011-09-01

The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

Feasible metabolisms in high pH springs of the Philippines.

Science.gov (United States)

Cardace, Dawn; Meyer-Dombard, D'Arcy R; Woycheese, Kristin M; Arcilla, Carlo A

2015-01-01

A field campaign targeting high pH, H2-, and CH4-emitting serpentinite-associated springs in the Zambales and Palawan Ophiolites of the Philippines was conducted in 2012-2013, and enabled description of several springs sourced in altered pillow basalts, gabbros, and peridotites. We combine field observations of pH, temperature, conductivity, dissolved oxygen, and oxidation-reduction potential with analyses of major ions, dissolved inorganic carbon, dissolved organic carbon, and dissolved gas phases in order to model the activities of selected phases important to microbial metabolism, and to rank feasible metabolic reactions based on energy yield. We document changing geochemical inventories in these springs between sampling years, and examine how the environment supports or prevents the function of certain microbial metabolisms. In all, this geochemistry-based assessment of feasible metabolisms indicates methane cycling, hydrogen oxidation, some iron and sulfur metabolisms, and ammonia oxidation are feasible reactions in this continental site of serpentinization.

Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

Directory of Open Access Journals (Sweden)

Kavitha S

2006-12-01

Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.

Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

Science.gov (United States)

Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

2016-10-01

This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

Science.gov (United States)

Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

2017-10-01

Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

Clouds-radiation interactions in a general circulation model - Impact upon the planetary radiation balance

Science.gov (United States)

Smith, Laura D.; Vonder Haar, Thomas H.

1991-01-01

Simultaneously conducted observations of the earth radiation budget and the cloud amount estimates, taken during the June 1979 - May 1980 Nimbus 7 mission were used to show interactions between the cloud amount and raidation and to verify a long-term climate simulation obtained with the latest version of the NCAR Community Climate Model (CCM). The parameterization of the radiative, dynamic, and thermodynamic processes produced the mean radiation and cloud quantities that were in reasonable agreement with satellite observations, but at the expense of simulating their short-term fluctuations. The results support the assumption that the inclusion of the cloud liquid water (ice) variable would be the best mean to reduce the blinking of clouds in NCAR CCM.

Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

Science.gov (United States)

Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

2017-01-01

Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification

NARCIS (Netherlands)

Dartel, van D.A.M.; Schulpen, S.H.; Theunissen, P.T.; Bunschoten, A.; Piersma, A.H.; Keijer, J.

2014-01-01

Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in

Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

Energy Technology Data Exchange (ETDEWEB)

Fisher, Oriana S. [Yale Univ., New Haven, CT (United States); Deng, Hanqiang [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China); Liu, Dou [Yale Univ. School of Medicine, New Haven, CT (United States); Zhang, Ya [Yale Univ. School of Medicine, New Haven, CT (United States); Wei, Rong [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China); Deng, Yong [Yale Univ. School of Medicine, New Haven, CT (United States); Zhang, Fan [Yale Univ. School of Medicine, New Haven, CT (United States); Louvi, Angeliki [Yale Univ. School of Medicine, New Haven, CT (United States); Turk, Benjamin E. [Yale Univ., New Haven, CT (United States); Boggon, Titus J. [Yale Univ., New Haven, CT (United States); Su, Bing [Shanghai Jiao Tong Univ. School of Medicine (SJTU-SM), Shanghai (China)

2015-08-03

Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystal structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.

Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

Science.gov (United States)

Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

2017-06-02

To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

Uptake and metabolism of carbohydrates by Bradyrhizobium japonicum bacteroids

International Nuclear Information System (INIS)

Salminen, S.O.; Streeter, J.G.

1987-01-01

Bradyrhizobium japonicum bacteroids were isolated anaerobically and were supplied with 14 C-labeled trehalose, sucrose, UDP-glucose, glucose, or fructose under low O 2 (2% in the gas phase). Uptake and conversion of 14 C to CO 2 were measured at intervals up to 90 minutes. Of the five compounds studied, UDP-glucose was most rapidly absorbed but it was very slowly metabolized. Trehalose was the sugar most rapidly converted to CO 2 , and fructose was respired at a rate of at least double that of glucose. Sucrose and glucose were converted to CO 2 at a very low but measurable rate ( 2 at a rate 30 times greater than the conversion of carbon Number 6 to CO 2 , indicating high activity of the pentose phosphate pathway. Enzymes of the Entner-Doudoroff pathway were not detected in bacteroids, but very low activities of sucrose synthase and phosphofructokinase were demonstrated. Although metabolism of sugars by B. japonicum bacteroids was clearly demonstrated, the rate of sugar uptake was only 1/30 to 1/50 the rate of succinate uptake. The overall results support the view that, although bacteroids metabolize sugars, the rates are very low and are inadequate to support nitrogenase

Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera.

Science.gov (United States)

Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

2016-01-01

The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK ( B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase ( B. longum ssp. longum CCDM 372).

In silico prediction of xenobiotic metabolism in humans

Energy Technology Data Exchange (ETDEWEB)

Mu, Fangping [Los Alamos National Laboratory

2009-01-01

Xenobiotic metabolism in humans is catalyzed by a few enzymes with broad substrate specificities, which provide the overall broad chemical specificity for nearly all xenobiotics that humans encounter. Xenobiotic metabolism are classified into functional group biotransformations. Based on bona fide reactions and negative examples for each reaction class, support vector machine (SVM) classifiers are built. The input to SVM is a set of atomic and molecular features to define the electrostatic, steric, energetic, geometrical and topological environment of the atoms in the reaction center under the molecule. Results show that the overall sensitivity and specificity of classifiers is around 87%.

Early differences in metabolic flexibility between obesity-resistant and obesity-prone mice

Czech Academy of Sciences Publication Activity Database

Bardová, Kristina; Horáková, Olga; Janovská, Petra; Hansíková, Jana; Kůs, Vladimír; van Schothorst, E. M.; Hoevenaars, F.P.M.; Uil, M.; Hensler, Michal; Keijer, J.; Kopecký, Jan

2016-01-01

Roč. 124, May (2016), s. 163-170 ISSN 0300-9084 R&D Projects: GA MŠk(CZ) 7E10059; GA ČR(CZ) GB14-36804G Institutional support: RVO:67985823 Keywords : indirect calorimetry * glucose tolerance * weaning * C57BL/6J mice * A/J mice * metabolic flexibility Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.112, year: 2016

SBOLme: a Repository of SBOL Parts for Metabolic Engineering

KAUST Repository

Kuwahara, Hiroyuki; Cui, Xuefeng; Umarov, Ramzan; Grunberg, Raik; Myers, Chris J.; Gao, Xin

2017-01-01

The Synthetic Biology Open Language (SBOL) is a community-driven open language to promote standardization in synthetic biology. To support the use of SBOL in metabolic engineering, we developed SBOLme, the first open-access repository of SBOL 2

A central role of eNOS in the protective effect of wine against metabolic syndrome.

Science.gov (United States)

Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

2006-01-01

The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic

Rufibacter ruber sp. nov., isolated from fragmentary rock

Czech Academy of Sciences Publication Activity Database

Kýrová, K.; Sedláček, I.; Pantůček, R.; Králová, S.; Holochová, P.; Mašlaňová, I.; Staňková, E.; Kleinhagauer, T.; Gelbíčková, T.; Sobotka, Roman; Švec, P.; Busse, H.-J.

2016-01-01

Roč. 66, č. 11 (2016), s. 4401-4405 ISSN 1466-5026 R&D Projects: GA MŠk(CZ) LO1416 Institutional support: RVO:61388971 Keywords : Gram-stain-negative * CCM 8646T * Rufibacter Subject RIV: EE - Microbiology, Virology Impact factor: 2.134, year: 2016

Integrated community case management for childhood illnesses: explaining policy resistance in Kenya.

Science.gov (United States)

Juma, Pamela A; Owuor, Karen; Bennett, Sara

2015-12-01

There has been a re-emphasis recently on community health workers to provide child health care services including integrated community case management for childhood illness (iCCM). This research analysed iCCM policy development in Kenya and in particular the types of decision-making criteria used by Kenyan policy-makers in considering whether to advance iCCM policy. Data were collected through document reviews (n = 41) and semi-structured interviews (n = 19) with key stakeholders in iCCM policy including government officials, development partners, bilateral donors, and civil society organizations. Initial analysis was guided by the policy triangle with further analysis of factors affecting policy decision-making drawing upon a simple framework developed by Grindle and Thomas (Policy makers, policy choices and policy outcomes: the political economy of reform in developing countries. 1989; Policy Sci 22: :213-48.). Policy development for iCCM has been slow in Kenya, compared with other Sub-Saharan African countries. At the time of the study, the Government had just completed the Community Health Training Manual which incorporated iCCM as a module, but this was the only formal expression of iCCM in Kenya. We found technical considerations, notably concerns about community health workers dispensing antibiotics to be a key factor slowing iCCM policy development, but this also overlapped with bureaucratic considerations, such as how the development of community health worker cadres may affect clinicians, as well as initial concerns about how an integrated approach might affect vertically oriented programs. International actors through agreements such as the Millennium Development Goals helped to get child survival onto the national policy agenda and such actors were active promoters of iCCM policy change. However international funders had not committed funding to scale-up iCCM policy, and this probably constrained their influence over iCCM policy debate. Kenyan actors

Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature.

Science.gov (United States)

Safavi, Maryam Sadat; Shojaosadati, Seyed Abbas; Yang, Hye Gyeong; Kim, Yejin; Park, Eun Ji; Lee, Kang Choon; Na, Dong Hee

2017-08-30

The purpose of this study was to prepare curcumin-loaded bovine serum albumin nanoparticles (CCM-BSA-NPs) by reducing agent-free self-assembly at room temperature. A 2 4 factorial design approach was used to investigate the CCM-BSA-NP preparation process at different pH values, temperatures, dithiothreitol amounts, and CCM/BSA mass ratios. Increasing the ionic strength enabled preparation of CCM-BSA-NPs at 25°C without reducing agent. CCM-BSA-NPs prepared under the optimized conditions at 25°C showed a particle size of 110±6nm, yield of 88.5%, and drug loading of 7.1%. The CCM-BSA-NPs showed strong antioxidant activity and neuroprotective effects in glutamate-induced mouse hippocampal neuronal HT22 cells. This study suggests that ionic strength can be a key parameter affecting the preparation of albumin-based NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolism of Ca and Sr in late adult life

International Nuclear Information System (INIS)

Newton, D.; Harrison, G.E.; Rundo, J.; Kang, C.; Warner, A.J.

1990-01-01

Data are presented on the metabolism of Ca and Sr in a healthy male volunteer who, in a series of investigations conducted between the ages of 53 and 82 y, received controlled intakes of 45 Ca, 47 Ca, or 85 Sr. No age-related trends were established, either in factors affecting the skeletal deposition of the tracers or in their subsequent retention studied for up to 462 d after intake. The data thus lend support to an important working postulate in the ICRP's model of alkaline earth metabolism

Medicare Chronic Care Management Payments and Financial Returns to Primary Care Practices: A Modeling Study.

Science.gov (United States)

Basu, Sanjay; Phillips, Russell S; Bitton, Asaf; Song, Zirui; Landon, Bruce E

2015-10-20

Physicians have traditionally been reimbursed for face-to-face visits. A new non-visit-based payment for chronic care management (CCM) of Medicare patients took effect in January 2015. To estimate financial implications of CCM payment for primary care practices. Microsimulation model incorporating national data on primary care use, staffing, expenditures, and reimbursements. National Ambulatory Medical Care Survey and other published sources. Medicare patients. 10 years. Practice-level. Comparison of CCM delivery approaches by staff and physicians. Net revenue per full-time equivalent (FTE) physician; time spent delivering CCM services. If nonphysician staff were to deliver CCM services, net revenue to practices would increase despite opportunity and staffing costs. Practices could expect approximately $332 per enrolled patient per year (95% CI, $234 to $429) if CCM services were delivered by registered nurses (RNs), approximately $372 (CI, $276 to $468) if services were delivered by licensed practical nurses, and approximately $385 (CI, $286 to $485) if services were delivered by medical assistants. For a typical practice, this equates to more than $75 ,00 of net annual revenue per FTE physician and 12 hours of nursing service time per week if 50% of eligible patients enroll. At a minimum, 131 Medicare patients (CI, 115 to 140 patients) must enroll for practices to recoup the salary and overhead costs of hiring a full-time RN to provide CCM services. If physicians were to deliver all CCM services, approximately 25% of practices nationwide could expect net revenue losses due to opportunity costs of face-to-face visit time. The CCM program may alter long-term primary care use, which is difficult to predict. Practices that rely on nonphysician team members to deliver CCM services will probably experience substantial net revenue gains but must enroll a sufficient number of eligible patients to recoup costs. None.

The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.

Science.gov (United States)

Caetano-Anollés, Gustavo; Kim, Hee Shin; Mittenthal, Jay E

2007-05-29

Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

Science.gov (United States)

Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

2015-04-01

Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

Development of clinical contents model markup language for electronic health records.

Science.gov (United States)

Yun, Ji-Hyun; Ahn, Sun-Ju; Kim, Yoon

2012-09-01

To develop dedicated markup language for clinical contents models (CCM) to facilitate the active use of CCM in electronic health record systems. Based on analysis of the structure and characteristics of CCM in the clinical domain, we designed extensible markup language (XML) based CCM markup language (CCML) schema manually. CCML faithfully reflects CCM in both the syntactic and semantic aspects. As this language is based on XML, it can be expressed and processed in computer systems and can be used in a technology-neutral way. CCML HAS THE FOLLOWING STRENGTHS: it is machine-readable and highly human-readable, it does not require a dedicated parser, and it can be applied for existing electronic health record systems.

Energy metabolism and the metabolic syndrome: does a lower basal metabolic rate signal recovery following weight loss?

Science.gov (United States)

Soares, Mario J; Cummings, Nicola K; Ping-Delfos, Wendy L Chan She

2011-01-01

To determine whether basal metabolic rate (BMR) was causally related to MetS, and to study the role of gender in this relationship. Seventy-two Caucasian subjects (43 women, 29 men) had changes in basal metabolic rate (BMR), carbohydrate oxidation rate (COR), fat oxidation rate (FOR) and prevalence of the metabolic syndrome (MetS) assessed in response to weight loss. There was a significant gender×MetS interaction in BMR at the start. Women with MetS had higher adjusted BMR, whilst men with MetS had lower adjusted BMR than their respective counterparts. Weight loss resulted in a significant decrease in fat mass (-5.2±0.31 kg, p=0.001), fat free mass (-2.3±0.27 kg, p=0.001), BMR (-549±58 kJ/d, p=0.001) and a decreased proportion of MetS (22/72, χ(2)=0.005). Subjects who recovered from MetS after weight loss (RMS) had ∼250 kJ/d significantly lower adjusted BMR compared to those who were never MetS (NMS, p=0.046) and those who still had MetS (MetS+, p=0.047). Regression analysis showed that change (Δ) in BMR was best determined by Δglucose×gender interaction (r(2)=23%), ΔFOR (r(2)=20.3%), ΔCOR (r(2)=19.4%) and Δtriglycerides (r(2)=7.8%). There is a sexual dimorphism of BMR in MetS. Overall, the data support the notion that alterations in BMR may be central to the etiopathogenesis of MetS. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Science.gov (United States)

Lamb, Joseph J; Holick, Michael F; Lerman, Robert H; Konda, Veera R; Minich, Deanna M; Desai, Anuradha; Chen, Tai C; Austin, Melissa; Kornberg, Jacob; Chang, Jyh-Lurn; Hsi, Alex; Bland, Jeffrey S; Tripp, Matthew L

2011-05-01

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Perceptions of a mobile health intervention for Community Case ...

African Journals Online (AJOL)

Journal Home > Vol 30, No 1 (2018) > ... quality of CCM delivery, and work efficiency as opportunities associated with using the ... records,, cumbersome duplicate assessments/data entry study procedures, and inconsistencies between the SL eCCM App and paper-based CCM guidelines as challenges to implementation.

Ecological relationship analysis of the urban metabolic system of Beijing, China

International Nuclear Information System (INIS)

Li Shengsheng; Zhang Yan; Yang Zhifeng; Liu Hong; Zhang Jinyun

2012-01-01

Cities can be modelled as giant organisms, with their own metabolic processes, and can therefore be studied using the same tools used for biological metabolic systems. The complicated distribution of compartments within these systems and the functional relationships among them define the system's network structure. Taking Beijing as an example, we divided the city's internal system into metabolic compartments, then used ecological network analysis to calculate a comprehensive utility matrix for the flows between compartments within Beijing's metabolic system from 1998 to 2007 and to identify the corresponding functional relationships among the system's compartments. Our results show how ecological network analysis, utility analysis, and relationship analysis can be used to discover the implied ecological relationships within a metabolic system, thereby providing insights into the system's internal metabolic processes. Such analyses provide scientific support for urban ecological management. - Highlights: ► Urban metabolic processes can be analyzed by treating cities as superorganisms. ► We developed an ecological network model for an urban system. ► We studied the system's network relationships using ecological network analysis. ► We developed indices for judging the system's synergism and degree of stability. - Using Beijing as an example of an urban superorganism, we used ecological network analysis to describe the ecological relationships among the urban metabolic system's compartments.

The Essential Role of Cholesterol Metabolism in the Intracellular Survival of Mycobacterium leprae Is Not Coupled to Central Carbon Metabolism and Energy Production.

Science.gov (United States)

Marques, Maria Angela M; Berrêdo-Pinho, Marcia; Rosa, Thabatta L S A; Pujari, Venugopal; Lemes, Robertha M R; Lery, Leticia M S; Silva, Carlos Adriano M; Guimarães, Ana Carolina R; Atella, Georgia C; Wheat, William H; Brennan, Patrick J; Crick, Dean C; Belisle, John T; Pessolani, Maria Cristina V

2015-12-01

Mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and Schwann cells. Cholesterol is among the lipids with increased abundance in M. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. The present study investigated the capacity of M. leprae to acquire and metabolize cholesterol. In silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), the first step of cholesterol degradation catalyzed by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD), is apparently the only portion of the cholesterol catabolic pathway seen in Mycobacterium tuberculosis preserved by M. leprae. Incubation of bacteria with radiolabeled cholesterol confirmed the in silico predictions. Radiorespirometry and lipid analyses performed after incubating M. leprae with [4-(14)C]cholesterol or [26-(14)C]cholesterol showed the inability of this pathogen to metabolize the sterol rings or the side chain of cholesterol as a source of energy and carbon. However, the bacteria avidly incorporated cholesterol and, as expected, converted it to cholestenone both in vitro and in vivo. Our data indicate that M. leprae has lost the capacity to degrade and utilize cholesterol as a nutritional source but retains the enzyme responsible for its oxidation to cholestenone. Thus, the essential role of cholesterol metabolism in the intracellular survival of M. leprae is uncoupled from central carbon metabolism and energy production. Further elucidation of cholesterol metabolism in the host cell during M. leprae infection will establish the mechanism by which this lipid supports M. leprae intracellular survival and will open new avenues for novel leprosy therapies. Our study focused on the obligate intracellular pathogen Mycobacterium leprae and its capacity to metabolize cholesterol. The data make an important contribution for those interested in understanding the

Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

Science.gov (United States)

Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

2015-08-20

The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Telmisartan as metabolic modulator: a new perspective in sports doping?

Science.gov (United States)

Sanchis-Gomar, Fabian; Lippi, Giuseppe

2012-03-01

The World Antidoping Agency (WADA) has introduced some changes in the 2012 prohibited list. Among the leading innovations to the rules are that both 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (peroxisome proliferator-activated receptor-δ [PPAR-δ]-5' adenosine monophosphate-activated protein kinase [AMPK] agonist) and GW1516 (PPAR-δ-agonist) are no longer categorized as gene doping substances in the new 2012 prohibited list but as metabolic modulators in the class "Hormone and metabolic modulators." This may also be valid for the angotensin II receptor blocker telmisartan. It has recently been shown that telmisartan might induce similar biochemical, biological, and metabolic changes (e.g., mitochondrial biogenesis and changes in skeletal muscle fiber type) as those reported for the former call of substances. We suspect that metabolic modulators abuse such as telmisartan might become a tangible threat in sports and should be thereby targeted as an important antidoping issue. The 2012 WADA prohibited list does not provide telmisartan for a potential doping drug, but arguments supporting the consideration to include them among "metabolic modulators" are at hand.

Community case management improves use of treatment for ...

African Journals Online (AJOL)

Objective: Evaluate the performance of volunteers in providing Community Case Management (CCM) for diarrhea, fever and pneumonia – in a pre-HEW setting in Liben Woreda, Oromiya Regional State. Methods: Save the Children supported Ministry of Health and communities to deliver child survival interventions from ...

Effects of independently altering body weight and body mass on the metabolic cost of running

NARCIS (Netherlands)

Teunissen, L.P.J.; Grabowski, A.; Kram, R.

2011-01-01

The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In

Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.

Science.gov (United States)

Carey, Maureen A; Papin, Jason A; Guler, Jennifer L

2017-07-19

Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P. falciparum parasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites, including folate and polyamines. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistant parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood. Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.

ANTIMICROBIAL ACTIVITY OF TUSSILAGO FARFARA L.

Directory of Open Access Journals (Sweden)

Miroslava Kačániová

2013-02-01

Full Text Available In this study, ethanolic extracts of Tussilago farfara L. which had been described in herbal books, were screened for their antimicrobial activity. The following strains of bacteria for antimicrobial activity were used Escherichia coli CCM 3988, Serratia rubidea CCM 4684, Staphylococcus epidermis CC 4418, Lactobacillus rhamnosus CCM 1828, Pseudomonas aeroginosa CCM 1960 and Enterococcus raffinosus CCM 4216. The yeast strain used in this study was Saccharomyces cerevisiae CCM 8191 using disc diffusion method and microbroth dilution technique. The highest antibacterial activity of Tussilago farfara L. ethanolic extract was measured in Grampositive bacteria Lactobacillus rhamnosus (6.67±1.53 mm and lower in yeast Saccharomyces cerevisiae (1.67±0.58 mm with disc diffusion method used. The ethanolic extract present an important activity against Saccharomyces cerevisiae (MIC50=24 µg.ml-1; MIC90=25.69 µg.ml-1 and Serratia rubidaea (MIC=48.01 µg.ml-1; MIC90=51.26 µg.ml-1 with microbroth dilution technique used.

Activating transcription factor 3 regulates immune and metabolic homeostasis

Czech Academy of Sciences Publication Activity Database

Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

2012-01-01

Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

Metabolic pathways of benzimidazole anthelmintics in harebell (Campanula rotundifolia)

Czech Academy of Sciences Publication Activity Database

Stuchlíková, L.; Jirásko, R.; Skálová, L.; Pavlík, F.; Szotáková, B.; Holčapek, M.; Vaněk, Tomáš; Podlipná, Radka

2016-01-01

Roč. 157, AUG (2016), s. 10-17 ISSN 0045-6535 R&D Projects: GA ČR(CZ) GA15-05325S Institutional support: RVO:61389030 Keywords : Drug metabolism * Biotransformation * Albendazole Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.208, year: 2016

Development and fabrication of membrane electrode assembly for PEM fuel cell

International Nuclear Information System (INIS)

Anjum, M.A.R.; Arshad, M.; Hussain, S.; Saeed, M.M.

2011-01-01

The 10 cm x 10 cm active area membrane electrode assembly (MEA) has been fabricated by adopting two routes, i.e., catalyst-coated membrane (CCM) and catalyst-coated support (CCS). In CCM method, the catalyst is directly applied on the Nafion membrane while in CCS method, catalyst is applied on support (GDL). The catalyst layer was prepared by nano-sized platinum on carbon particle, the ionomer material of the membrane and a solvent that allows the catalyst to behave like ink. The catalyst slurry was applied on the membrane, hot-pressed the sandwich of GDL and catalyst-coated Nafion membrane to form a single unit which behaves as electrodes. The primary tests regarding the efficiency of indigenously-fabricated MEAs have been carried out successfully. The performance of MEA with respect to continuous operation for long hours from the standpoint of proper functioning was also checked. A maximum power of 13 watt was obtained. (author)

Horizontal and vertical growth of S. cerevisiae metabolic network.

KAUST Repository

Grassi, Luigi

2011-10-14

BACKGROUND: The growth and development of a biological organism is reflected by its metabolic network, the evolution of which relies on the essential gene duplication mechanism. There are two current views about the evolution of metabolic networks. The retrograde model hypothesizes that a pathway evolves by recruiting novel enzymes in a direction opposite to the metabolic flow. The patchwork model is instead based on the assumption that the evolution is based on the exploitation of broad-specificity enzymes capable of catalysing a variety of metabolic reactions. RESULTS: We analysed a well-studied unicellular eukaryotic organism, S. cerevisiae, and studied the effect of the removal of paralogous gene products on its metabolic network. Our results, obtained using different paralog and network definitions, show that, after an initial period when gene duplication was indeed instrumental in expanding the metabolic space, the latter reached an equilibrium and subsequent gene duplications were used as a source of more specialized enzymes rather than as a source of novel reactions. We also show that the switch between the two evolutionary strategies in S. cerevisiae can be dated to about 350 million years ago. CONCLUSIONS: Our data, obtained through a novel analysis methodology, strongly supports the hypothesis that the patchwork model better explains the more recent evolution of the S. cerevisiae metabolic network. Interestingly, the effects of a patchwork strategy acting before the Euascomycete-Hemiascomycete divergence are still detectable today.

Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

Science.gov (United States)

Mulvihill, Erin E; Burke, Amy C; Huff, Murray W

2016-07-17

Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

Uric acid in metabolic syndrome: From an innocent bystander to a central player

Science.gov (United States)

Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

2016-01-01

Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies.

Science.gov (United States)

O'Grady, John; Schwender, Jörg; Shachar-Hill, Yair; Morgan, John A

2012-03-01

For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (13)CO(2) dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

Variation in winter metabolic reduction between sympatric amphibians

Czech Academy of Sciences Publication Activity Database

Podhajský, Luděk; Gvoždík, Lumír

2016-01-01

Roč. 201, November (2016), s. 110-114 ISSN 1095-6433 R&D Projects: GA ČR(CZ) GA15-07140S Institutional support: RVO:68081766 Keywords : Caloric reserves * Ichthyosaura * Lissotriton * Metabolic rate * Newt * Oxygen consumption * Respirometry * Salamander * Thermal sensitivity * Wintering Subject RIV: EG - Zoology Impact factor: 1.812, year: 2016

Preliminary results of Physiological plant growth modelling for human life support in space

Science.gov (United States)

Sasidharan L, Swathy; Dussap, Claude-Gilles; Hezard, Pauline

2012-07-01

Human life support is fundamental and crucial in any kind of space explorations. MELiSSA project of European Space Agency aims at developing a closed, artificial ecological life support system involving human, plants and micro organisms. Consuming carbon dioxide and water from the life support system, plants grow in one of the chambers and convert it into food and oxygen along with potable water. The environmental conditions, nutrient availability and its consumption of plants should be studied and necessarily modeled to predict the amount of food, oxygen and water with respect to the environmental changes and limitations. The reliability of a completely closed system mainly depends on the control laws and strategies used. An efficient control can occur, only if the system to control is itself well known, described and ideally if the responses of the system to environmental changes are predictable. In this aspect, the general structure of plant growth model has been designed together with physiological modelling.The physiological model consists of metabolic models of leaves, stem and roots, of which concern specific metabolisms of the associated plant parts. On the basis of the carbon source transport (eg. sucrose) through stem, the metabolic models (leaf and root) can be interconnected to each other and finally coupled to obtain the entire plant model. For the first step, leaf metabolic model network was built using stoichiometric, mass and energy balanced metabolic equations under steady state approach considering all necessary plant pathways for growth and maintenance of leaves. As the experimental data for lettuce plants grown in closed and controlled environmental chambers were available, the leaf metabolic model has been established for lettuce leaves. The constructed metabolic network is analyzed using known stoichiometric metabolic technique called metabolic flux analysis (MFA). Though, the leaf metabolic model alone is not sufficient to achieve the

Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

International Nuclear Information System (INIS)

Eilon, Tali; Barash, Itamar

2008-01-01

Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip ® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. At least

Human breath analysis may support the existence of individual metabolic phenotypes.

Directory of Open Access Journals (Sweden)

Pablo Martinez-Lozano Sinues

Full Text Available The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

Resuscitation Prior to Emergency Endotracheal Intubation: Results of a National Survey

Directory of Open Access Journals (Sweden)

Robert S. Green

2016-09-01

Full Text Available Introduction: Respiratory failure is a common problem in emergency medicine (EM and critical care medicine (CCM. However, little is known about the resuscitation of critically ill patients prior to emergency endotracheal intubation (EETI. Our aim was to describe the resuscitation practices of EM and CCM physicians prior to EETI. Methods: A cross-sectional survey was developed and tested for content validity and retest reliability by members of the Canadian Critical Care Trials Group. The questionnaire was distributed to all EM and CCM physician members of three national organizations. Using three clinical scenarios (trauma, pneumonia, congestive heart failure, we assessed physician preferences for use and types of fluid and vasopressor medication in pre-EETI resuscitation of critically ill patients. Results: In total, 1,758 physicians were surveyed (response rate 50.2%, 882/1,758. Overall, physicians would perform pre-EETI resuscitation using either fluids or vasopressors in 54% (1,193/2,203 of cases. Most physicians would “always/often” administer intravenous fluid pre-EETI in the three clinical scenarios (81%, 1,484/1,830. Crystalloids were the most common fluid physicians would “always/often” administer in congestive heart failure (EM 43%; CCM 44%, pneumonia (EM 97%; CCM 95% and trauma (EM 96%; CCM 96%. Pre-EETI resuscitation using vasopressors was uncommon (4.9%. Training in CCM was associated with performing pre-EETI resuscitation (odds ratio, 2.20; 95% CI, [1.44-3.36], p<0.001. Conclusion: Pre-EETI resuscitation is common among Canadian EM and CCM physicians. Most physicians use crystalloids pre-EETI as a resuscitation fluid, while few would give vasopressors. Physicians with CCM training were more likely to perform pre-EETI resuscitation.

Assessment of the monitoring and evaluation system for integrated community case management (ICCM) in Ethiopia: a comparison against global benchmark indicators.

Science.gov (United States)

Mamo, Dereje; Hazel, Elizabeth; Lemma, Israel; Guenther, Tanya; Bekele, Abeba; Demeke, Berhanu

2014-10-01

Program managers require feasible, timely, reliable, and valid measures of iCCM implementation to identify problems and assess progress. The global iCCM Task Force developed benchmark indicators to guide implementers to develop or improve monitoring and evaluation (M&E) systems. To assesses Ethiopia's iCCM M&E system by determining the availability and feasibility of the iCCM benchmark indicators. We conducted a desk review of iCCM policy documents, monitoring tools, survey reports, and other rele- vant documents; and key informant interviews with government and implementing partners involved in iCCM scale-up and M&E. Currently, Ethiopia collects data to inform most (70% [33/47]) iCCM benchmark indicators, and modest extra effort could boost this to 83% (39/47). Eight (17%) are not available given the current system. Most benchmark indicators that track coordination and policy, human resources, service delivery and referral, supervision, and quality assurance are available through the routine monitoring systems or periodic surveys. Indicators for supply chain management are less available due to limited consumption data and a weak link with treatment data. Little information is available on iCCM costs. Benchmark indicators can detail the status of iCCM implementation; however, some indicators may not fit country priorities, and others may be difficult to collect. The government of Ethiopia and partners should review and prioritize the benchmark indicators to determine which should be included in the routine M&E system, especially since iCCMdata are being reviewed for addition to the HMIS. Moreover, the Health Extension Worker's reporting burden can be minimized by an integrated reporting approach.

Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data.

Science.gov (United States)

Horne, Margaret A; Flemming, Kelly D; Su, I-Chang; Stapf, Christian; Jeon, Jin Pyeong; Li, Da; Maxwell, Susanne S; White, Philip; Christianson, Teresa J; Agid, Ronit; Cho, Won-Sang; Oh, Chang Wan; Wu, Zhen; Zhang, Jun-Ting; Kim, Jeong Eun; Ter Brugge, Karel; Willinsky, Robert; Brown, Robert D; Murray, Gordon D; Al-Shahi Salman, Rustam

2016-02-01

Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7-17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2-9·7) and with brainstem CCM location versus other locations (4·4, 2·3-8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1-5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1-15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3-23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3-35·2) for 495 people with brainstem CCM presenting with ICH or FND. Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These

Collaborative care model improves self-care ability, quality of life and cardiac function of patients with chronic heart failure

Directory of Open Access Journals (Sweden)

C.Y. Hua

2017-09-01

Full Text Available Chronic heart failure (CHF is a common chronic disease that requires much care. This study aimed to explore the effects of collaborative care model (CCM on patients with CHF. A total of 114 CHF patients were enrolled in this study, and were randomly and equally divided into two groups: control and experimental. Patients in the two groups received either usual care or CCM for 3 continuous months. The impacts of CCM on the self-care ability and quality of life were assessed using self-care of heart failure index and short form health survey 12, respectively. Further, cardiac function was assessed by measuring left ventricular ejection fraction (LVEF and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP, and by the 6-min walking test. Clinical and demographic characteristics of patients in the control and CCM groups were statistically equivalent. Compared with usual care, CCM significantly enhanced self-care abilities of patients with CHF, including self-care maintenance, self-care management and self-care confidence (all P<0.05. The physical and mental quality of life was also significantly improved by CCM (P<0.01 or P<0.05. Compared with usual care, CCM significantly increased the LVEF (P<0.01, decreased the NT-proBNP level (P<0.01, and enhanced exercise capacity (P<0.001. In conclusion, CCM improved the self-care, quality of life and cardiac function of patients with CHF compared with usual care.

Integrating Cellular Metabolism into a Multiscale Whole-Body Model

Science.gov (United States)

Krauss, Markus; Schaller, Stephan; Borchers, Steffen; Findeisen, Rolf; Lippert, Jörg; Kuepfer, Lars

2012-01-01

Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development. PMID:23133351

Double silencing of relevant genes suggests the existence of the direct link between DNA replication/repair and central carbon metabolism in human fibroblasts.

Science.gov (United States)

Wieczorek, Aneta; Fornalewicz, Karolina; Mocarski, Łukasz; Łyżeń, Robert; Węgrzyn, Grzegorz

2018-04-15

Genetic evidence for a link between DNA replication and glycolysis has been demonstrated a decade ago in Bacillus subtilis, where temperature-sensitive mutations in genes coding for replication proteins could be suppressed by mutations in genes of glycolytic enzymes. Then, a strong influence of dysfunctions of particular enzymes from the central carbon metabolism (CCM) on DNA replication and repair in Escherichia coli was reported. Therefore, we asked if such a link occurs only in bacteria or it is a more general phenomenon. Here, we demonstrate that effects of silencing (provoked by siRNA) of expression of genes coding for proteins involved in DNA replication and repair (primase, DNA polymerase ι, ligase IV, and topoisomerase IIIβ) on these processes (less efficient entry into the S phase of the cell cycle and decreased level of DNA synthesis) could be suppressed by silencing of specific genes of enzymes from CMM. Silencing of other pairs of replication/repair and CMM genes resulted in enhancement of the negative effects of lower expression levels of replication/repair genes. We suggest that these results may be proposed as a genetic evidence for the link between DNA replication/repair and CMM in human cells, indicating that it is a common biological phenomenon, occurring from bacteria to humans. Copyright © 2018 Elsevier B.V. All rights reserved.

What is Metabolic Syndrome?

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... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

Metabolic Effects of Intermittent Fasting.

Science.gov (United States)

Patterson, Ruth E; Sears, Dorothy D

2017-08-21

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

Science.gov (United States)

Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

2017-09-05

The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

Directory of Open Access Journals (Sweden)

Jon C Svendsen

Full Text Available Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons. Using juvenile lake sturgeon (Acipenser fulvescens, the objective of this study was to test four hypotheses: 1 A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2 A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3 measurements of forced maximum metabolic rate (MMR(F are repeatable in individual fish; and 4 MMR(F correlates positively with spontaneous maximum metabolic rate (MMR(S. Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMR(F. Trials lasting 24 h were used to measure standard metabolic rate (SMR and MMR(S. Repeatability and correlations between MMR(F and MMR(S were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O(2sat, demonstrating oxygen regulation. In contrast, MMR(F was affected by hypoxia and decreased across the range from 100% O(2sat to 70% O(2sat. MMR(F was repeatable in individual fish, and MMR(F correlated positively with MMR(S, but the relationships between MMR(F and MMR(S were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor. Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMR(F and MMR(S support the conjecture that MMR(F represents a measure of organism performance that could be a target of natural selection.

Computational Modelling of the Metabolic States Regulated by the Kinase Akt

Directory of Open Access Journals (Sweden)

Ettore eMosca

2012-11-01

Full Text Available Signal transduction pathways and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB, also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modelled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production and nucleotide biosynthesis. We used a computational model in order to compare two metabolic states generated by the specific variation of the metabolic fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One of the two states represented the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis, while the other state represented the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism, as reported in literature in relation to the activity of the PI3K/Akt/mTOR. Some steps that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism.

Letter report: Cold crucible melter assessment

International Nuclear Information System (INIS)

Elliott, M.L.

1996-03-01

One of the activities of the PNL Vitrification Technology Development (PVTD) Project is to assist the Tank Waste Remediation Systems (TWRS) Program in determining which melter systems should be performance tested for potential implementation in the high-level waste (HLW) vitrification plant. The Richland Operations Office (RL) has recommended that the Cold Crucible Melter (CCM) be evaluated as a candidate ''next generation'' melter. As a result, the CCM System Evaluation cost account was established under the PVTD Project so that the CCM could be initially assessed on a high-priority basis. This letter report summarizes a brief initial review and assessment of the CCM. Using the recommendations made in this document, Westinghouse Hanford Company (WHC) and RL will make a decision regarding the urgency of performance testing the CCM. If the decision is favorable, a subcontract will be negotiated for performance testing of a CCM using Hanford HLW simulants in a pilot-scale facility. Because of the aggressive nature of the schedule, the CCM evaluation was not rigorous. The evaluation consisted of a literature review and interviews with proponents of the technology during a recent trip to France. This letter report summarizes the evaluation and makes recommendations regarding further work in this area

A study on the carotid artery ultrasonography for the metabolic syndrome

International Nuclear Information System (INIS)

Kong, Hye Jung; Cho, Pyong Kon; Kang, Young Han

2013-01-01

The primary goal of this study was to ascertain the primary factors to the affect for the carotid artery intima-media thickness (IMT), the prevalence of metabolic syndrome and other risks can possibly influence the carotid artery IMT. All patients data (total specimens: 289, male: 197, female: 92) including the carotid artery ultrasonography examination. The all data were analyzed by the use of SPSS software, version 21.0 (SPSS, Chicago, IL USA), with the descriptive statistics method. The Results of this study was found to be highly increased in the males than the females. The prevalence of metabolic syndrome in all of the participants was 30.5 percentages. The carotid artery IMT in the subjects with metabolic syndrome was significantly high in both genders, compared to the rest, who were without metabolic syndrome. The Pearsons correlation coefficient of metabolic syndrome and CIMT was 0.378(p<0.01). In conclusions, the present study also supports the association between the carotid artery IMT and the metabolic syndromes with cardiovascular risk factors. Usage of B-mode ultrasonography to measure the carotid artery IMT was found to be highly effective in the current analysis

A study on the carotid artery ultrasonography for the metabolic syndrome

Energy Technology Data Exchange (ETDEWEB)

Kong, Hye Jung; Cho, Pyong Kon [Dept. of Radiological Science, Catholic University of Daegu, Daegu (Korea, Republic of); Kang, Young Han [Dept. of Radiology, Catholic University Hospital of Daegu, Daegu (Korea, Republic of)

2013-09-15

The primary goal of this study was to ascertain the primary factors to the affect for the carotid artery intima-media thickness (IMT), the prevalence of metabolic syndrome and other risks can possibly influence the carotid artery IMT. All patients data (total specimens: 289, male: 197, female: 92) including the carotid artery ultrasonography examination. The all data were analyzed by the use of SPSS software, version 21.0 (SPSS, Chicago, IL USA), with the descriptive statistics method. The Results of this study was found to be highly increased in the males than the females. The prevalence of metabolic syndrome in all of the participants was 30.5 percentages. The carotid artery IMT in the subjects with metabolic syndrome was significantly high in both genders, compared to the rest, who were without metabolic syndrome. The Pearsons correlation coefficient of metabolic syndrome and CIMT was 0.378(p<0.01). In conclusions, the present study also supports the association between the carotid artery IMT and the metabolic syndromes with cardiovascular risk factors. Usage of B-mode ultrasonography to measure the carotid artery IMT was found to be highly effective in the current analysis.

Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome.

Science.gov (United States)

Smith, Caitlin J; Ryckman, Kelli K

2015-01-01

Metabolic syndrome is a growing cause of morbidity and mortality worldwide. Metabolic syndrome is characterized by the presence of a variety of metabolic disturbances including obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar. Although the risk for metabolic syndrome has largely been attributed to adult lifestyle factors such as poor nutrition, lack of exercise, and smoking, there is now strong evidence suggesting that predisposition to the development of metabolic syndrome begins in utero. First posited by Hales and Barker in 1992, the "thrifty phenotype" hypothesis proposes that susceptibility to adult chronic diseases can occur in response to exposures in the prenatal and perinatal periods. This hypothesis has been continually supported by epidemiologic studies and studies involving animal models. In this review, we describe the structural, metabolic and epigenetic changes that occur in response to adverse intrauterine environments including prenatal and postnatal diet, maternal obesity, and pregnancy complications. Given the increasing prevalence of metabolic syndrome in both the developed and developing worlds, a greater understanding and appreciation for the role of the intrauterine environment in adult chronic disease etiology is imperative.

Identification and characterization of a carboxysomal γ-carbonic anhydrase from the cyanobacterium Nostoc sp. PCC 7120.

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de Araujo, Charlotte; Arefeen, Dewan; Tadesse, Yohannes; Long, Benedict M; Price, G Dean; Rowlett, Roger S; Kimber, Matthew S; Espie, George S

2014-09-01

Carboxysomes are proteinaceous microcompartments that encapsulate carbonic anhydrase (CA) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco); carboxysomes, therefore, catalyze reversible HCO3 (-) dehydration and the subsequent fixation of CO2. The N- and C-terminal domains of the β-carboxysome scaffold protein CcmM participate in a network of protein-protein interactions that are essential for carboxysome biogenesis, organization, and function. The N-terminal domain of CcmM in the thermophile Thermosynechococcus elongatus BP-1 is also a catalytically active, redox regulated γ-CA. To experimentally determine if CcmM from a mesophilic cyanobacterium is active, we cloned, expressed and purified recombinant, full-length CcmM from Nostoc sp. PCC 7120 as well as the N-terminal 209 amino acid γ-CA-like domain. Both recombinant proteins displayed ethoxyzolamide-sensitive CA activity in mass spectrometric assays, as did the carboxysome-enriched TP fraction. NstCcmM209 was characterized as a moderately active and efficient γ-CA with a k cat of 2.0 × 10(4) s(-1) and k cat/K m of 4.1 × 10(6) M(-1) s(-1) at 25 °C and pH 8, a pH optimum between 8 and 9.5 and a temperature optimum spanning 25-35 °C. NstCcmM209 also catalyzed the hydrolysis of the CO2 analog carbonyl sulfide. Circular dichroism and intrinsic tryptophan fluorescence analysis demonstrated that NstCcmM209 was progressively and irreversibly denatured above 50 °C. NstCcmM209 activity was inhibited by the reducing agent tris(hydroxymethyl)phosphine, an effect that was fully reversed by a molar excess of diamide, a thiol oxidizing agent, consistent with oxidative activation being a universal regulatory mechanism of CcmM orthologs. Immunogold electron microscopy and Western blot analysis of TP pellets indicated that Rubisco and CcmM co-localize and are concentrated in Nostoc sp. PCC 7120 carboxysomes.

Metabolic acclimation to excess light intensity in Chlamydomonas reinhardtii.

Science.gov (United States)

Davis, Maria C; Fiehn, Oliver; Durnford, Dion G

2013-07-01

There are several well-described acclimation responses to excess light in green algae but the effect on metabolism has not been thoroughly investigated. This study examines the metabolic changes during photoacclimation to high-light (HL) stress in Chlamydomonas reinhardtii using nuclear magnetic resonance and mass spectrometry. Using principal component analysis, a clear metabolic response to HL intensity was observed on global metabolite pools, with major changes in the levels of amino acids and related nitrogen metabolites. Amino acid pools increased during short-term photoacclimation, but were especially prominent in HL-acclimated cultures. Unexpectedly, we observed an increase in mitochondrial metabolism through downstream photorespiratory pathways. The expression of two genes encoding key enzymes in the photorespiratory pathway, glycolate dehydrogenase and malate synthase, were highly responsive to the HL stress. We propose that this pathway contributes to metabolite pools involved in nitrogen assimilation and may play a direct role in photoacclimation. Our results suggest that primary and secondary metabolism is highly pliable and plays a critical role in coping with the energetic imbalance during HL exposure and a necessary adjustment to support an increased growth rate that is an effective energy sink for the excess reducing power generated during HL stress. © 2013 John Wiley & Sons Ltd.

Metabolism

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... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine.

Science.gov (United States)

Aurich, Maike K; Thiele, Ines

2016-01-01

Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine.

Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies.

Science.gov (United States)

Kalnenieks, Uldis; Pentjuss, Agris; Rutkis, Reinis; Stalidzans, Egils; Fell, David A

2014-01-01

Mathematical modeling of metabolism is essential for rational metabolic engineering. The present work focuses on several types of modeling approach to quantitative understanding of central metabolic network and energetics in the bioethanol-producing bacterium Zymomonas mobilis. Combined use of Flux Balance, Elementary Flux Mode, and thermodynamic analysis of its central metabolism, together with dynamic modeling of the core catabolic pathways, can help to design novel substrate and product pathways by systematically analyzing the solution space for metabolic engineering, and yields insights into the function of metabolic network, hardly achievable without applying modeling tools.

Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

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Sebastiano Collino

Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

Metabolism

Science.gov (United States)

... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

Uncovering transcriptional regulation of metabolism by using metabolic network topology

DEFF Research Database (Denmark)

Patil, Kiran Raosaheb; Nielsen, Jens

2005-01-01

in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

[Metabolic acidosis].

Science.gov (United States)

Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

2016-01-01

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

The Protein Cost of Metabolic Fluxes: Prediction from Enzymatic Rate Laws and Cost Minimization.

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Elad Noor

2016-11-01

Full Text Available Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain metabolic enzymes. The necessary enzyme amount per unit flux is a major determinant of metabolic strategies both in evolution and bioengineering. It depends on enzyme parameters (such as kcat and KM constants, but also on metabolite concentrations. Moreover, similar amounts of different enzymes might incur different costs for the cell, depending on enzyme-specific properties such as protein size and half-life. Here, we developed enzyme cost minimization (ECM, a scalable method for computing enzyme amounts that support a given metabolic flux at a minimal protein cost. The complex interplay of enzyme and metabolite concentrations, e.g. through thermodynamic driving forces and enzyme saturation, would make it hard to solve this optimization problem directly. By treating enzyme cost as a function of metabolite levels, we formulated ECM as a numerically tractable, convex optimization problem. Its tiered approach allows for building models at different levels of detail, depending on the amount of available data. Validating our method with measured metabolite and protein levels in E. coli central metabolism, we found typical prediction fold errors of 4.1 and 2.6, respectively, for the two kinds of data. This result from the cost-optimized metabolic state is significantly better than randomly sampled metabolite profiles, supporting the hypothesis that enzyme cost is important for the fitness of E. coli. ECM can be used to predict enzyme levels and protein cost in natural and engineered pathways, and could be a valuable computational tool to assist metabolic engineering projects. Furthermore, it establishes a direct connection between protein cost and thermodynamics, and provides a physically plausible and computationally tractable way to include enzyme kinetics into constraint-based metabolic models, where kinetics have usually been ignored or

Lipid signaling in adipose tissue: Connecting inflammation & metabolism

Czech Academy of Sciences Publication Activity Database

Masoodi, M.; Kuda, Ondřej; Rossmeisl, Martin; Flachs, Pavel; Kopecký, Jan

2015-01-01

Roč. 1851, č. 4 (2015), s. 503-518 ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E12073; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipocyte * futile substrate cycle * macrophage Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.779, year: 2015

Dietary Interventions and Changes in Cardio-Metabolic Parameters in Metabolically Healthy Obese Subjects: A Systematic Review with Meta-Analysis

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Marta Stelmach-Mardas

2016-07-01

Full Text Available The aim of this systematic review was to assess the effect of diet on changes in parameters describing the body size phenotype of metabolically healthy obese subjects. The databases Medline, Scopus, Web of Knowledge and Embase were searched for clinical studies carried out between 1958 and June 2016 that reported the effect of dietary intervention on BMI, blood pressure, concentration of fasting triglyceride (TG, high density lipoprotein cholesterol (HDL-C, fasting glucose level, the homoeostatic model assessment of insulin resistance (HOMA-IR and high sensitivity C-Reactive Protein (hsCRP in metabolically healthy, obese subjects. Twelve clinical studies met inclusion criteria. The combined analyzed population consists of 1827 subjects aged 34.4 to 61.1 with a BMI > 30 kg/m2. Time of intervention ranged from eight to 104 weeks. The baseline characteristics related to lipid profile were more favorable for metabolically healthy obese than for metabolically unhealthy obese. The meta-analyses revealed a significant associations between restricted energy diet and BMI (95% confidence interval (CI: −0.88, −0.19, blood pressure (systolic blood pressure (SBP: −4.73 mmHg; 95% CI: −7.12, −2.33; and diastolic blood pressure (DBP: −2.75 mmHg; 95% CI: −4.30, −1.21 and TG (−0.11 mmol/l; 95% CI: −0.16, −0.06. Changes in fasting glucose, HOMA-IR and hsCRP did not show significant changes. Sufficient evidence was not found to support the use of specific diets in metabolically healthy obese subjects. This analysis suggests that the effect of caloric restriction exerts its effects through a reduction in BMI, blood pressure and triglycerides in metabolically healthy obese (MHO patients.

Pulmonary metabolism of foreign compounds: Its role in metabolic activation

International Nuclear Information System (INIS)

Cohen, G.M.

1990-01-01

The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity

The way forward for integrated community case managementprogrammes: A summary of lessons learned to date and future priorities

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Mark Young

2014-11-01

Full Text Available Integrated community case management (iCCM programming is an important and increasingly common strategy used to deliver essential health and nutrition interventions to families in sub–Saharan Africa. Between 3 and 5 March 2014, over 400 individuals from 35 countries in sub–Saharan Africa and 59 international partner organisations gathered in Accra, Ghana for an iCCM Evidence Review Symposium. The objective of the Symposium was twofold: first, to review the current state of the art of iCCM implementation by bringing together researchers, donors, government, implementers and partners to review the map of the current landscape and status of evidence in key iCCM programme areas, in order to draw out priorities, lessons and gaps for improving child and maternal–newborn health and nutrition. Second, to assist African countries to integrate and take action on key frontline iCCM findings presented during the evidence Symposium around eight thematic areas: 1 Coordination, Policy Setting and Scale up; 2 Human Resources and Deployment; 3 Supervision & Performance Quality Assurance; 4 Supply Chain Management; 5 Costs, and cost-effectiveness and financing; 6 Monitoring, Evaluation and Health Information Systems; 7 Demand generation and social mobilisation; and 8 Impact and outcome evaluations. The eight thematic areas were based on the CCM benchmark framework, a tool for iCCM program planners and managers to systematically design and implement iCCM programs from the early phases through expansion and scale up. The framework specifies key steps that should be completed for each component and phase of implementation.

Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

Science.gov (United States)

Kim, Woonsu; Park, Hyesun; Seo, Seongwon

2016-01-01

The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID

Tissue-Specific Peroxisome Proliferator Activated Receptor Gamma Expression and Metabolic Effects of Telmisartan

Czech Academy of Sciences Publication Activity Database

Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Landa, Vladimír; Kazdová, L.; Pravenec, Michal; Kurtz, T. W.

2013-01-01

Roč. 26, č. 6 (2013), s. 829-835 ISSN 0895-7061 R&D Projects: GA ČR(CZ) GAP303/10/0505; GA MŠk(CZ) LH11049; GA MŠk(CZ) LL1204; GA MŠk(CZ) 7E10067 Institutional support: RVO:67985823 Keywords : telmisartan * metabolic effects * tissue-specific Pparg knockout mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.402, year: 2013

Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

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Olivier F. Noel

2016-01-01

Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.

Science.gov (United States)

de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Verheijen, Mark H G; Posthuma, Danielle

2015-11-01

Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.

Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

Science.gov (United States)

McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

2015-09-01

Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Metabolism of γ-hydroxyl-[1-14C] butyrate by rat brain: relationship to the Krebs cycle and metabolic compartmentation of amino acids

International Nuclear Information System (INIS)

Doherty, J.D.; Roth, R.H.

1978-01-01

Ninhydrin decarboxylation experiments were carried out on the labelled amino acids produced following intraventricular injection of either γ-hydroxy-[1- 14 C] butyric acid (GHB) or [1- 14 C] succinate. The loss of isotope (as 14 CO 2 ) was similar for both substances. The [1- 14 C] GHB metabolites lost 75% of the label and the [1- 14 C] succinate metabolites lost 68%. This observation gives support to the hypothesis that the rat brain has the enzymatic capacity to metabolize [1- 14 C] GHB to succinate and to amino acids that have the isotope in the carboxylic acid group adjacent to the α-amino group. These results also indicate that the label from [1- 14 C] GHB does not enter the Krebs cycle as acetate. The specific activity ratio of radio-labelled glutamine to glutamic acid was determined in order to evaluate which of the two major metabolic compartments prefentially metabolize GHB. It was found that for [1- 14 C] GHB the ratio was 4.20 +- 0.18 (S.E. for n = 7) and for [1- 14 C] succinate the ratio was 7.71 (average of two trials, 7.74 and 7.69). These results suggest that the compartment thought to be associated with glial cells and synaptosomal structures is largely responsible for the metabolism of GHB. Metabolism as it might relate to the neuropharmacological action of GHB is discussed. (author)

Obestatin as a regulator of adipocyte metabolism and adipogenesis

Science.gov (United States)

Gurriarán-Rodríguez, Uxía; Al-Massadi, Omar; Roca-Rivada, Arturo; Crujeiras, Ana Belén; Gallego, Rosalía; Pardo, Maria; Seoane, Luisa Maria; Pazos, Yolanda; Casanueva, Felipe F; Camiña, Jesús P

2011-01-01

Abstract The role of obestatin, a 23-amino-acid peptide encoded by the ghrelin gene, on the control of the metabolism of pre-adipocyte and adipocytes as well as on adipogenesis was determined. For in vitro assays, pre-adipocyte and adipocyte 3T3-L1 cells were used to assess the obestatin effect on cell metabolism and adipogenesis based on the regulation of the key enzymatic nodes, Akt and AMPK and their downstream targets. For in vivo assays, white adipose tissue (WAT) was obtained from male rats under continuous subcutaneous infusion of obestatin. Obestatin activated Akt and its downstream targets, GSK3α/β, mTOR and S6K1, in 3T3-L1 adipocyte cells. Simultaneously, obestatin inactivated AMPK in this cell model. In keeping with this, ACC phosphorylation was also decreased. This fact was confirmed in vivo in white adipose tissue (omental, subcutaneous and gonadal) obtained from male rats under continuous sc infusion of obestatin (24 and 72 hrs). The relevance of obestatin as regulator of adipocyte metabolism was supported by AS160 phosphorylation, GLUT4 translocation and augment of glucose uptake in 3T3-L1 adipocyte cells. In contrast, obestatin failed to modify translocation of fatty acid transporters, FATP1, FATP4 and FAT/CD36, to plasma membrane. Obestatin treatment in combination with IBMX and DEX showed to regulate the expression of C/EBPα, C/EBPβ, C/EBPδ and PPARγ promoting adipogenesis. Remarkable, preproghrelin expression, and thus obestatin expression, increased during adipogenesis being sustained throughout terminal differentiation. Neutralization of endogenous obestatin secreted by 3T3-L1 cells by anti-obestatin antibody decreased adipocyte differentiation. Furthermore, knockdown experiments by preproghrelin siRNA supported that obestatin contributes to adipogenesis. In summary, obestatin promotes adipogenesis in an autocrine/paracrine manner, being a regulator of adipocyte metabolism. These data point to a putative role in the pathogenesis of

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

Science.gov (United States)

Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

2007-11-01

1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH 120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

International Nuclear Information System (INIS)

Altenburg, Jeffrey D; Bieberich, Andrew A; Terry, Colin; Harvey, Kevin A; VanHorn, Justin F; Xu, Zhidong; Jo Davisson, V; Siddiqui, Rafat A

2011-01-01

Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED 50 . Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER - PR - Her2 + ) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes

Opposite metabolic responses of shoots and roots to drought

Czech Academy of Sciences Publication Activity Database

Gargallo-Garriga, A.; Sardans, J.; Pérez-Trujillo, M.; Rivas-Ubach, A.; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Jentsch, A.; Kreyling, J.; Beierkuhnlein, C.; Parella, T.; Penuelas, J.

2014-01-01

Roč. 4, č. 6829 (2014), s. 1-7 ISSN 2045-2322 Grant - others:AV ČR(CZ) M200871201 Institutional support: RVO:67179843 Keywords : shoot and roots * autotrophic and heterotrophic organs * environmental change * growth metabolism * water and nutirens Subject RIV: EH - Ecology, Behaviour Impact factor: 5.578, year: 2014

Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension

Czech Academy of Sciences Publication Activity Database

Plecitá-Hlavatá, Lydie; Tauber, Jan; Li, M.; Zhang, H.; Flockton, A. R.; Pullamsetti, S. S.; Chelladurai, P.; D'Alessandro, A.; El Kasmi, K. C.; Ježek, Petr; Stenmark, K. R.

2016-01-01

Roč. 55, č. 1 (2016), s. 47-57 ISSN 1044-1549 R&D Projects: GA MŠk(CZ) LH11055; GA MŠk(CZ) LH15071 Institutional support: RVO:67985823 Keywords : mitochondria * complex I * oxidative metabolism * pulmonary hypertension * adventitial fibroblasts Subject RIV: ED - Physiology Impact factor: 4.100, year: 2016

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

Science.gov (United States)

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-01-01

Metabolic homeostasis is regulated by the brain, whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipids levels. Importantly, this function of metabolic learning requires not only the mushroom body but the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. PMID:25848677

An Integrative Approach to Energy, Carbon, and Redox Metabolism in the Cyanobacterium Synechocystis sp. PCC 6803. Special Report

Energy Technology Data Exchange (ETDEWEB)

Overbeek, R.

2003-06-30

The main objectives for the first year were to produce a detailed metabolic reconstruction of synechocystis sp. PCC 6803 especially in interrelated areas of photosynthesis, respiration, and central carbon metabolism to support a more complete understanding and modeling of this organism. Additionally, Integrated Genomics, Inc., provided detailed bioinformatic analysis of selected functional systems related to carbon and energy generation and utilization, and of the corresponding pathways, functional roles and individual genes to support wet lab experiments by collaborators.

A clustering analysis of lipoprotein diameters in the metabolic syndrome

Science.gov (United States)

The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

Abdominal obesity and metabolic syndrome: exercise as medicine?

Science.gov (United States)

Paley, Carole A; Johnson, Mark I

2018-01-01

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

Science.gov (United States)

Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

2015-12-01

Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

Metabolic basis of ethanol-induced cytotoxicity in recombinant HepG2 cells: Role of nonoxidative metabolism

International Nuclear Information System (INIS)

Wu Hai; Cai Ping; Clemens, Dahn L.; Jerrells, Thomas R.; Ansari, G.A. Shakeel; Kaphalia, Bhupendra S.

2006-01-01

. VA-13 cells incubated with ethanol appears to be mediated by release of mitochondrial cytochrome c via activation of caspase-9 and caspase-3. These results strongly support our hypothesis that diminished hepatic ADH activity facilitates nonoxidative metabolism of ethanol and the products of ethanol nonoxidative metabolism cause apoptosis in HepG2 cells via intrinsic pathway

Engineering Cellular Metabolism

DEFF Research Database (Denmark)

Nielsen, Jens; Keasling, Jay

2016-01-01

Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

It must be my metabolism: Metabolic control of mind

Directory of Open Access Journals (Sweden)

Dana M Small

2014-07-01

participant ingested the same caloric dose during conditioning, changes in plasma glucose depended upon individual differences in glucose absorption/metabolism. Therefore, these findings provide indirect, and yet convincing, support for our hypothesis that glucose metabolism regulates response to calorie-predictive flavors in brain reward circuits. We can therefore conclude that, at least for carbohydrates, responses to calorie predictive food cues reflect the learned association between the cue and its ability to result in a change in blood glucose. This finding has important implications for understanding how the modern food environment promotes weight gain. Carbohydrates now come in forms and doses not experienced during our evolutionary past. Not only are calories increased, but the way in which they are metabolized differs. For example, calories ingested in liquid form are trafficked through the gut faster than solids (e.g. 18. Might this influence metabolic regulation of reward circuits? Certainly it stands to reason that larger loads delivered more quickly to the circulation might increase the metabolic impact and hence more efficiently engage reward circuits to enhance food cue reactivity and promote eating in the absence of hunger. In summary, our result indicates that, as in the rodent model, metabolic response drives the reinforcement potency of carbohydrates and regulates food cue reactivity. We conclude that not only are modern foods more caloric, but in addition their increased metabolic impact drives reward circuits and may therefore promote intake by enhancing food cue reactivity. Our finding further suggests that metabolic regulation of reward circuits may differ in individuals with altered glucose metabolism, such as type II diabetes, offering a potential mechanism by which they become susceptible to weight gain.

Feasible Metabolic Schema Associated with High pH Springs in the Philippines

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DAWN eCARDACE

2015-02-01

Full Text Available A field campaign targeting high pH springs in the Zambales and Palawan Ophiolites of the Philippines was conducted in 2012-2013, and enabled description of several springs sourced in altered pillow basalts, gabbros, and peridotites. We combine field observations of pH, temperature, conductivity, dissolved oxygen, and oxidation-reduction potential with analyses of major ions, dissolved inorganic carbon, dissolved organic carbon, and dissolved gas phases in order to model the activities of selected phases important to microbial metabolism, and to evaluate feasible metabolic reactions based on energy yield. We document changing geochemical inventories in these springs, and examine how the environment supports or prevents the function of certain microbial metabolisms.

Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

Science.gov (United States)

Zholudeva, Lyandysha V.; Ward, Kristina G.; Nichols, Michael G.; Smith, Heather Jensen

2015-05-01

Aminoglycoside antibiotics are implicated as culprits of hearing loss in more than 120,000 individuals annually. Research has shown that the sensory cells, but not supporting cells, of the cochlea are readily damaged and/or lost after use of such antibiotics. High-frequency outer hair cells (OHCs) show a greater sensitivity to antibiotics than high- and low-frequency inner hair cells (IHCs). We hypothesize that variations in mitochondrial metabolism account for differences in susceptibility. Fluorescence lifetime microscopy was used to quantify changes in NAD(P)H in sensory and supporting cells from explanted murine cochleae exposed to mitochondrial uncouplers, inhibitors, and an ototoxic antibiotic, gentamicin (GM). Changes in metabolic state resulted in a redistribution of NAD(P)H between subcellular fluorescence lifetime pools. Supporting cells had a significantly longer lifetime than sensory cells. Pretreatment with GM increased NAD(P)H intensity in high-frequency sensory cells, as well as the NAD(P)H lifetime within IHCs. GM specifically increased NAD(P)H concentration in high-frequency OHCs, but not in IHCs or pillar cells. Variations in NAD(P)H intensity in response to mitochondrial toxins and GM were greatest in high-frequency OHCs. These results demonstrate that GM rapidly alters mitochondrial metabolism, differentially modulates cell metabolism, and provides evidence that GM-induced changes in metabolism are significant and greatest in high-frequency OHCs.

Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

Directory of Open Access Journals (Sweden)

Anja Karlstaedt

2018-06-01

Full Text Available Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

Carbohydrate Metabolism Disorders

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... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

Integrating cellular metabolism into a multiscale whole-body model.

Directory of Open Access Journals (Sweden)

Markus Krauss

Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

Czech Academy of Sciences Publication Activity Database

Tomasetti, M.; Amati, M.; Santarelli, L.; Neužil, Jiří

2016-01-01

Roč. 17, č. 5 (2016), č. článku 754. E-ISSN 1422-0067 Institutional support: RVO:86652036 Keywords : miRNAs * tumorigenesis * miR-126 and cancer-stroma environment * metabolic reprogramming Subject RIV: EB - Genetics ; Molecular Biology

Energy Metabolism and Human Dosimetry of Tritium

International Nuclear Information System (INIS)

Galeriu, D.; Takeda, H.; Melintescu, A.; Trivedi, A.

2005-01-01

In the frame of current revision of human dosimetry of 14 C and tritium, undertaken by the International Commission of Radiological Protection, we propose a novel approach based on energy metabolism and a simple biokinetic model for the dynamics of dietary intake (organic 14 C, tritiated water and Organically Bound Tritium-OBT). The model predicts increased doses for HTO and OBT comparing to ICRP recommendations, supporting recent findings

Effect of psychosocial factors on metabolic syndrome in male and female blue-collar workers.

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Hwang, Won Ju; Lee, Chung Yul

2014-01-01

The purposes of this study were to examine the relationship between psychosocial factors and metabolic syndrome among male and female blue-collar workers, and which factors influence their metabolic syndrome by sex. A cross-sectional study was completed of 154 men and 80 women working at small companies in Korea. The data were collected through a structured questionnaire, blood test, and anthropometric and blood pressure measure. Metabolic syndrome was diagnosed from the results of blood test and the measurements of waist circumference and blood pressure. The prevalence of metabolic syndrome among male and female blue-collar workers was 24.0% and 7.5%, respectively. Multiple logistic regression analysis was performed to examine factors of metabolic syndrome associated with sex. After controlling for age, marital status, smoking, alcohol drinking, shift work, overtime work, and physical exercise, job stress (odds ratio [OR] = 3.10, P = 0.005) and risk perception (OR = 1.12, P = 0.016) were influencing factors for men, and low job stress (OR = 0.05, P = 0.04), low social support (OR = 1.51, P = 0.009), and risk perception (OR = 1.27, P = 0.023) for women. Metabolic syndrome among blue-collar workers is closely related to psychosocial factors, such as job stress, social support, and risk perception, with the effect of job stress a point of difference between men and women. Occupational health nurses should be cognizant of the importance of assessing the effect of psychosocial factors on cardiovascular risk for blue-collar workers. © 2012 The Authors. Japan Journal of Nursing Science © 2012 Japan Academy of Nursing Science.

Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome

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Smith CJ

2015-06-01

Full Text Available Caitlin J Smith, Kelli K Ryckman Department of Epidemiology, University of Iowa, College of Public Health, Iowa City, IA, USA Abstract: Metabolic syndrome is a growing cause of morbidity and mortality worldwide. Metabolic syndrome is characterized by the presence of a variety of metabolic disturbances including obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar. Although the risk for metabolic syndrome has largely been attributed to adult lifestyle factors such as poor nutrition, lack of exercise, and smoking, there is now strong evidence suggesting that predisposition to the development of metabolic syndrome begins in utero. First posited by Hales and Barker in 1992, the “thrifty phenotype” hypothesis proposes that susceptibility to adult chronic diseases can occur in response to exposures in the prenatal and perinatal periods. This hypothesis has been continually supported by epidemiologic studies and studies involving animal models. In this review, we describe the structural, metabolic and epigenetic changes that occur in response to adverse intrauterine environments including prenatal and postnatal diet, maternal obesity, and pregnancy complications. Given the increasing prevalence of metabolic syndrome in both the developed and developing worlds, a greater understanding and appreciation for the role of the intrauterine environment in adult chronic disease etiology is imperative. Keywords: epigenetics, metabolic syndrome, fetal programming, maternal, pregnancy complications

Metabolic response to feeding in Tupinambis merianae: circadian rhythm and a possible respiratory constraint.

Science.gov (United States)

Klein, Wilfried; Perry, Steven F; Abe, Augusto S; Andrade, Denis V

2006-01-01

The diurnal tegu lizard Tupinambis merianae exhibits a marked circadian variation in metabolism that is characterized by the significant increase in metabolism during part of the day. These increases in metabolic rate, found in the fasting animal, are absent during the first 2 d after meal ingestion but reappear subsequently, and the daily increase in metabolic rate is added to the increase in metabolic rate caused by digestion. During the first 2 d after feeding, priority is given to digestion, while on the third and following days, the metabolic demands are clearly added to each other. This response seems to be a regulated response of the animal, which becomes less active after food ingestion, rather than an inability of the respiratory system to support simultaneous demands at the beginning of digestion. The body cavity of Tupinambis is divided into two compartments by a posthepatic septum (PHS). Animals that had their PHS surgically removed showed no significant alteration in the postprandial metabolic response compared to tegus with intact PHS. The maximal metabolic increment during digestion, the relative cost of meal digestion, and the duration of the process were virtually unaffected by the removal of the PHS.

Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

Science.gov (United States)

Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

2015-04-07

Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

The energy metabolism of megacities

International Nuclear Information System (INIS)

Facchini, Angelo; Kennedy, Chris; Stewart, Iain; Mele, Renata

2017-01-01

Highlights: • Energy metabolism leads to a better management of energy use in megacities. • Insights on strategies to improve energy efficiency and reduce resource consumption. • We find a regionalization of energy flows and sectoral energy use. • Scaling law for energy Vs density suggests strategies for compact cities planning. • Supports development of models to reduce GHG emissions and increase resilience. - Abstract: Due to their sheer size and complexity, megacities are extreme examples in which both negative and positive aspects of urbanization co-exist and are amplified. Especially in emerging countries they are becoming the dominant paradigm of the future urbanization, representing a sustainability challenge both from the point of view of energy and resource consumption, and from the point of view of climate change adaptation and mitigation. In this paper we compare the energy metabolism in 27 of the world’s megacities including details of mobile and stationary energy consumption patterns, fuels used, as well as end-use patterns and electricity generation mix. Our results show that per capita total energy consumption scales with urban population density according to a power law characterized by the universal −3/4 scaling, pointing out that compact cities are more energy efficient with respect to dispersed cities. By comparing energy sources and sectoral end use, also focusing on electricity use and generation source, we found a significant regionalization of energy metabolism, and we discuss the implication for resilience, infrastructure planning, GHG emissions, and policies for infrastructure decarbonization. The comparison of the energy metabolism can lead to a more appropriate management of energy use patterns and electricity generation mix in megacities, giving insights on strategies to improve urban energy efficiency and reducing environmental pressure of megacities.

Metabolic oxidative stress in cancer biology and therapy

International Nuclear Information System (INIS)

Spitz, Douglas R.

2014-01-01

Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate.

Science.gov (United States)

Valdebenito, Rocío; Ruminot, Iván; Garrido-Gerter, Pamela; Fernández-Moncada, Ignacio; Forero-Quintero, Linda; Alegría, Karin; Becker, Holger M; Deitmer, Joachim W; Barros, L Felipe

2016-10-01

The effectiveness of ketogenic diets and intermittent fasting against neurological disorders has brought interest to the effects of ketone bodies on brain cells. These compounds are known to modify the metabolism of neurons, but little is known about their effect on astrocytes, cells that control the supply of glucose to neurons and also modulate neuronal excitability through the glycolytic production of lactate. Here we have used genetically-encoded Förster Resonance Energy Transfer nanosensors for glucose, pyruvate and ATP to characterize astrocytic energy metabolism at cellular resolution. Our results show that the ketone body beta-hydroxybutyrate strongly inhibited astrocytic glucose consumption in mouse astrocytes in mixed cultures, in organotypic hippocampal slices and in acute hippocampal slices prepared from ketotic mice, while blunting the stimulation of glycolysis by physiological and pathophysiological stimuli. The inhibition of glycolysis was paralleled by an increased ability of astrocytic mitochondria to metabolize pyruvate. These results support the emerging notion that astrocytes contribute to the neuroprotective effect of ketone bodies. © The Author(s) 2015.

Obesity and metabolic syndrome in COPD: Is exercise the answer?

Science.gov (United States)

James, Benjamin D; Jones, Amy V; Trethewey, Ruth E; Evans, Rachael A

2018-05-01

Approximately half of all patients with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation (PR) programmes are overweight or obese which negatively impacts upon dyspnoea and exercise tolerance particularly when walking. Within the obese population (without COPD), the observed heterogeneity in prognosis is in part explained by the variability in the risk of developing cardiovascular disease or diabetes (cardiometabolic risk) leading to the description of metabolic syndrome. In obesity alone, high-intensity aerobic training can support healthy weight loss and improve the constituent components of metabolic syndrome. Those with COPD, obesity and/or metabolic syndrome undergoing PR appear to do as well in traditional outcomes as their normal-weight metabolically healthy peers in terms of improvement of symptoms, health-related quality of life and exercise performance, and should therefore not be excluded. To broaden the benefit of PR, for this complex population, we should learn from the extensive literature examining the effects of exercise in obesity and metabolic syndrome discussed in this review and optimize the exercise strategy to improve these co-morbid conditions. Standard PR outcomes could be expanded to include cardiometabolic risk reduction to lower future morbidity and mortality; to this end exercise may well be the answer.

Metabolism of methylamine in the tea plant (Thea sinensis L.)

Science.gov (United States)

Suzuki, Takeo

1973-01-01

1. The metabolism of methylamine in excised shoot tips of tea was studied with micromolar amounts of [14C]methylamine. Of the [14C]methylamine supplied 57% was utilized by tea shoots during the 10h experimental period. 2. The main products of [14C]methylamine metabolism in tea shoots were serine, γ-glutamylmethylamide, theobromine, caffeine and CO2. There was also incorporation of the label into glutamate, aspartate, RNA purine nucleotides and S-adenosylmethionine. 3. The formation of methylamine from γ-glutamylmethylamide was confirmed by feeding tea shoots with γ-glutamyl[14C]methylamide. The products of γ-glutamyl[14C]methylamide metabolism in tea plants were serine, theobromine, caffeine, glutamate and aspartate. 4. The results indicate that the oxidation of methylamine to formaldehyde is the first step of methylamine utilization. Labelled formaldehyde released by the metabolism of methylamine leads to the incorporation of the label into metabolites on the C1 pathways of this compound. It is also suggested that formaldehyde is further oxidized via formate to CO2. 5. The role of γ-glutamylmethylamide in methylamine metabolism in tea plants is discussed. 6. Results support the view that theobromine is the immediate precursor of caffeine. PMID:4721610

Convergent cross-mapping and pairwise asymmetric inference.

Science.gov (United States)

McCracken, James M; Weigel, Robert S

2014-12-01

Convergent cross-mapping (CCM) is a technique for computing specific kinds of correlations between sets of times series. It was introduced by Sugihara et al. [Science 338, 496 (2012).] and is reported to be "a necessary condition for causation" capable of distinguishing causality from standard correlation. We show that the relationships between CCM correlations proposed by Sugihara et al. do not, in general, agree with intuitive concepts of "driving" and as such should not be considered indicative of causality. It is shown that the fact that the CCM algorithm implies causality is a function of system parameters for simple linear and nonlinear systems. For example, in a circuit containing a single resistor and inductor, both voltage and current can be identified as the driver depending on the frequency of the source voltage. It is shown that the CCM algorithm, however, can be modified to identify relationships between pairs of time series that are consistent with intuition for the considered example systems for which CCM causality analysis provided nonintuitive driver identifications. This modification of the CCM algorithm is introduced as "pairwise asymmetric inference" (PAI) and examples of its use are presented.

Myocardial metabolism, perfusion, wall motion and electrical activity in Duchenne muscular dystrophy

International Nuclear Information System (INIS)

Perloff, J.K.; Henze, E.; Schelbert, H.R.

1982-01-01

The cardiomyopathy of Duchenne's muscular dystrophy originates in the posterobasal left ventricle and extends chiefly to the contiguous lateral wall. Ultrastructural abnormalities in these regions precede connective tissue replacement. We postulated that a metabolic fault coincided with or antedated the subcellular abnormality. Accordingly, regional left ventricular metabolism, perfusion and wall motion were studied using positron computed tomography and metabolic isotopes supplemented by thallium perfusion scans, equilibrium radionuclide angiography and M-mode and two-dimensional echocardiography. To complete the assessment, electrocardiograms, vectorcardiograms, 24 hour taped electrocardiograms and chest x-rays were analyzed. Positron computed tomography utilizing F-18 2-fluoro 2-deoxyglucose (FDG) provided the first conclusive evidence supporting the hypothesis of a premorphologic regional metabolic fault. Thus, cardiac involvement in duchenne dystrophy emerges as a unique form of heart disease, genetically targeting specific regions of ventricular myocardium for initial metabolic and subcellular changes. Reported ultrastructural abnormalities of the impulse and conduction systems provide, at least in part, a basis for the clinically observed sinus node, intraatrial, internodal, AV nodal and infranodal disorders

Animal metabolism

International Nuclear Information System (INIS)

Walburg, H.E.

1977-01-01

Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

Metabolic Myopathies.

Science.gov (United States)

Tarnopolsky, Mark A

2016-12-01

Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

Community dialogues for child health: results from a qualitative process evaluation in three countries.

Science.gov (United States)

Martin, Sandrine; Leitão, Jordana; Muhangi, Denis; Nuwa, Anthony; Magul, Dieterio; Counihan, Helen

2017-06-05

Across the developing world, countries are increasingly adopting the integrated community case management of childhood illnesses (iCCM) strategy in efforts to reduce child mortality. This intervention's effectiveness is dependent on community adoption and changes in care-seeking practices. We assessed the implementation process of a theory-driven community dialogue (CD) intervention specifically designed to strengthen the support and uptake of the newly introduced iCCM services and related behaviours in three African countries. A qualitative process evaluation methodology was chosen and used secondary project data and primary data collected in two districts of each of the three countries, in purposefully sampled communities. The final data set included 67 focus group discussions and 57 key informant interviews, totalling 642 respondents, including caregivers, CD facilitators community leaders, and trainers. Thematic analysis of the data followed the 'Framework Approach' utilising both a deduction and induction process. Results show that CDs contribute to triggering community uptake of and support for iCCM services through filling health information gaps and building cooperation within communities. We found it to be an effective approach for addressing social norms around child care practices. This approach was embraced by communities for its flexibility and value in planning individual and collective change. Regular CDs can contribute to the formation of new habits, particularly in relation to seeking timely care in case of child sickness. This study also confirms the value of process evaluation to unwrap the mechanisms of community mobilisation approaches in context and provides key insights for improving the CD approach.

Quality of relationships with parents and friends in adolescence predicts metabolic risk in young adulthood.

Science.gov (United States)

Ehrlich, Katherine B; Hoyt, Lindsay Till; Sumner, Jennifer A; McDade, Thomas W; Adam, Emma K

2015-09-01

This study was designed to examine whether family and peer relationships in adolescence predict the emergence of metabolic risk factors in young adulthood. Participants from a large, nationally representative cohort study (N = 11,617 for these analyses) reported on their relationship experiences with parents and close friends during adolescence. Fourteen years later, interviewers collected blood samples, as well as anthropometric and blood pressure measurements. Blood samples were analyzed for HbA1c. Ordered logistic regressions revealed that for females, supportive parent-child relationships and close male friendships in adolescence were associated with reduced odds of having elevated metabolic risk markers in young adulthood. These effects remained significant even after controlling for baseline measures of body mass index (BMI) and health and demographic covariates. The protective effects of close relationships were not significant for males, however. Exploratory analyses with 2-parent families revealed that supportive father-child relationships were especially protective for females. These findings suggest that, for females, close and supportive relationships with parents and male friends in adolescence may reduce the risk of metabolic dysregulation in adulthood. (c) 2015 APA, all rights reserved).

The use of metabolic balance studies in the objective discrimination between intestinal insufficiency and intestinal failure

DEFF Research Database (Denmark)

Prahm, August P; Brandt, Christopher F; Askov-Hansen, Carsten

2017-01-01

Background: In research settings that use metabolic balance studies (MBSs) of stable adult patients with short bowel syndrome, intestinal failure (IF) and dependence on parenteral support (PS) have been defined objectively as energy absorption metabolic rate (BMR), wet......, to objectivize the cause of nutritional dyshomeostasis (oral failure, malabsorption, or both), and to quantify the effects of treatment....

Species-specific pharmacology of antiestrogens: role of metabolism

International Nuclear Information System (INIS)

Jordan, V.C.; Robinson, S.P.

1987-01-01

The nonsteroidal antiestrogen tamoxifen exhibits a paradoxial space species pharmacology. The drug is a full estrogen in the mouse, a partial estrogen/antiestrogen in humans and the rat, and an antiestrogen in the chick oviduct. Inasmuch as tamoxifen has antiestrogenic effects in vitro, differential metabolism of tamoxifen to estrogens might occur in the species in which it has antiestrogen pharmacology. Tamoxifen or its metabolite 4-hydroxytamoxifen could lose the alkylaminoethane side chain to form the estrogenic compound metabolite E of bisphenol. Sensitive metabolic studies with [ 3 H]tamoxifen in chicks, rats, and mice identified 4-hydroxytamoxifen as the major metabolite. Athymic mice with transplanted human breast tumors can be used to study the ability of tamoxifen to stimulate tissue or tumor growth. Estradiol caused the growth of transplanted breast cancer cells into solid tumors and a uterotrophic response. However, tamoxifen does not support tumor growth when administered alone, although it stimulates uterines growth. Since a similar profile of metabolites is sequestered in human mouse tissues, these studies strongly support the concept that the drug can selectively stimulate or inhibit events in the target tissues of different species without hometabolic intervention

Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.

Science.gov (United States)

Ando, David; Garcia Martin, Hector

2018-01-01

Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is critical to achieving rapid and facile bioengineering of organisms for the production of, e.g., biofuels and other chemicals. The Learn phase involves using data obtained from the Test phase to inform the next Design phase. As part of the Learn phase, mathematical models of metabolic fluxes give a mechanistic level of comprehension to cellular metabolism, isolating the principle drivers of metabolic behavior from the peripheral ones, and directing future experimental designs and engineering methodologies. Furthermore, the measurement of intracellular metabolic fluxes is specifically noteworthy as providing a rapid and easy-to-understand picture of how carbon and energy flow throughout the cell. Here, we present a detailed guide to performing metabolic flux analysis in the Learn phase of the DBTL cycle, where we show how one can take the isotope labeling data from a 13 C labeling experiment and immediately turn it into a determination of cellular fluxes that points in the direction of genetic engineering strategies that will advance the metabolic engineering process.For our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative Metabolic Modeling (jQMM) library, which provides an open-source, python-based framework for modeling internal metabolic fluxes and making actionable predictions on how to modify cellular metabolism for specific bioengineering goals. It presents a complete toolbox for performing different types of flux analysis such as Flux Balance Analysis, 13 C Metabolic Flux Analysis, and it introduces the capability to use 13 C labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) [1]. In addition to several other capabilities, the jQMM is also able to predict the effects of knockouts using the MoMA and ROOM methodologies. The use of the jQMM library is

Nutritional support management in premature infant in a Mexican (Guanajuato) hospital.

OpenAIRE

Monroy-Torres, R.; Mendoza Hernández, A. N.; Ruiz González, S. R.

2012-01-01

Introduction: Premature infant has special nutritional and physiological recommendations. Nutritional support promotes an appropriate weight gain. While this support is monitored according to international guidelines, the metabolic and infectious complicationscan be reduced and prevented.Objective: To describe the management of nutritional support in premature infant in a Mexican (Guana juato) hospital.Methods: A descriptive cross-sectional study, where a survey of 22 questions was applied by...

Comprehensive metabolic panel

Science.gov (United States)

Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

Novel Composite Membrane for Space Life Supporting System, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Space life-supporting systems require effective removal of metabolic CO2 from the cabin atmosphere with minimal loss of O2. Conventional techniques, using either...

Short peptide based nanotubes capable of effective curcumin delivery for treating drug resistant malaria.

Science.gov (United States)

Alam, Shadab; Panda, Jiban Jyoti; Mukherjee, Tapan Kumar; Chauhan, Virander Singh

2016-04-05

Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine-α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC50, 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC50, 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an

The role of astrocytic glycogen in supporting the energetics of neuronal activity.

Science.gov (United States)

Dinuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

2012-11-01

Energy homeostasis in the brain is maintained by oxidative metabolism of glucose, primarily to fulfil the energy demand associated with ionic movements in neurons and astrocytes. In this contribution we review the experimental evidence that grounds a specific role of glycogen metabolism in supporting the functional energetic needs of astrocytes during the removal of extracellular potassium. Based on theoretical considerations, we further discuss the hypothesis that the mobilization of glycogen in astrocytes serves the purpose to enhance the availability of glucose for neuronal glycolytic and oxidative metabolism at the onset of stimulation. Finally, we provide an evolutionary perspective for explaining the selection of glycogen as carbohydrate reserve in the energy-sensing machinery of cell metabolism.

A state of the art of metabolic networks of unicellular microalgae and cyanobacteria for biofuel production.

Science.gov (United States)

Baroukh, Caroline; Muñoz-Tamayo, Rafael; Steyer, Jean-Philippe; Bernard, Olivier

2015-07-01

The most promising and yet challenging application of microalgae and cyanobacteria is the production of renewable energy: biodiesel from microalgae triacylglycerols and bioethanol from cyanobacteria carbohydrates. A thorough understanding of microalgal and cyanobacterial metabolism is necessary to master and optimize biofuel production yields. To this end, systems biology and metabolic modeling have proven to be very efficient tools if supported by an accurate knowledge of the metabolic network. However, unlike heterotrophic microorganisms that utilize the same substrate for energy and as carbon source, microalgae and cyanobacteria require light for energy and inorganic carbon (CO2 or bicarbonate) as carbon source. This double specificity, together with the complex mechanisms of light capture, makes the representation of metabolic network nonstandard. Here, we review the existing metabolic networks of photoautotrophic microalgae and cyanobacteria. We highlight how these networks have been useful for gaining insight on photoautotrophic metabolism. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Metabolic Signaling and Therapy of Lung Cancer

Science.gov (United States)

2013-09-01

report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...which makes them attractive therapeutic targets. However, the development of targeted agents in lung cancer is still in its infancy, despite the...notion that metabolites can act as signaling molecules in distant metabolic pathways is gaining significant attentionand support (Figure 1A). Some of the

Ovarian tumor-initiating cells display a flexible metabolism

International Nuclear Information System (INIS)

Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

2014-01-01

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

Ovarian tumor-initiating cells display a flexible metabolism

Energy Technology Data Exchange (ETDEWEB)

Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

2014-10-15

An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

Metabolic heat production by human and animal populations in cities

Science.gov (United States)

Stewart, Iain D.; Kennedy, Chris A.

2017-07-01

Anthropogenic heating from building energy use, vehicle fuel consumption, and human metabolism is a key term in the urban energy budget equation. Heating from human metabolism, however, is often excluded from urban energy budgets because it is widely observed to be negligible. Few reports for low-latitude cities are available to support this observation, and no reports exist on the contribution of domestic animals to urban heat budgets. To provide a more comprehensive view of metabolic heating in cities, we quantified all terms of the anthropogenic heat budget at metropolitan scale for the world's 26 largest cities, using a top-down statistical approach. Results show that metabolic heat release from human populations in mid-latitude cities (e.g. London, Tokyo, New York) accounts for 4-8% of annual anthropogenic heating, compared to 10-45% in high-density tropical cities (e.g. Cairo, Dhaka, Kolkata). Heat release from animal populations amounts to <1% of anthropogenic heating in all cities. Heat flux density from human and animal metabolism combined is highest in Mumbai—the world's most densely populated megacity—at 6.5 W m-2, surpassing heat production by electricity use in buildings (5.8 W m-2) and fuel combustion in vehicles (3.9 W m-2). These findings, along with recent output from global climate models, suggest that in the world's largest and most crowded cities, heat emissions from human metabolism alone can force measurable change in mean annual temperature at regional scale.

Metabolic heat production by human and animal populations in cities.

Science.gov (United States)

Stewart, Iain D; Kennedy, Chris A

2017-07-01

Anthropogenic heating from building energy use, vehicle fuel consumption, and human metabolism is a key term in the urban energy budget equation. Heating from human metabolism, however, is often excluded from urban energy budgets because it is widely observed to be negligible. Few reports for low-latitude cities are available to support this observation, and no reports exist on the contribution of domestic animals to urban heat budgets. To provide a more comprehensive view of metabolic heating in cities, we quantified all terms of the anthropogenic heat budget at metropolitan scale for the world's 26 largest cities, using a top-down statistical approach. Results show that metabolic heat release from human populations in mid-latitude cities (e.g. London, Tokyo, New York) accounts for 4-8% of annual anthropogenic heating, compared to 10-45% in high-density tropical cities (e.g. Cairo, Dhaka, Kolkata). Heat release from animal populations amounts to heating in all cities. Heat flux density from human and animal metabolism combined is highest in Mumbai-the world's most densely populated megacity-at 6.5 W m -2 , surpassing heat production by electricity use in buildings (5.8 W m -2 ) and fuel combustion in vehicles (3.9 W m -2 ). These findings, along with recent output from global climate models, suggest that in the world's largest and most crowded cities, heat emissions from human metabolism alone can force measurable change in mean annual temperature at regional scale.

The Aging Clock and Circadian Control of Metabolism and Genome Stability

Directory of Open Access Journals (Sweden)

Victoria P. Belancio

2015-01-01

Full Text Available It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

Energy Technology Data Exchange (ETDEWEB)

Bremer, J; Davis, E J

1973-01-01

The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

Hepatocytes in the development of liver support systems

NARCIS (Netherlands)

I.H.M. Borel Rinkes (Inne)

1993-01-01

textabstractThis thesis focuses on the development of alternative strategies in the treatment of patients with acute fulminant hepatic failure and inborn errors of metabolism, using hepatocytes as the basis of liver support. When compared with transplantation of the liver as an organ, the

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Directory of Open Access Journals (Sweden)

Lucio Della Guardia

2018-05-01

Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

The metabolic cost of human running: is swinging the arms worth it?

Science.gov (United States)

Arellano, Christopher J; Kram, Rodger

2014-07-15

Although the mechanical function is quite clear, there is no consensus regarding the metabolic benefit of arm swing during human running. We compared the metabolic cost of running using normal arm swing with the metabolic cost of running while restricting the arms in three different ways: (1) holding the hands with the arms behind the back in a relaxed position (BACK), (2) holding the arms across the chest (CHEST) and (3) holding the hands on top of the head (HEAD). We hypothesized that running without arm swing would demand a greater metabolic cost than running with arm swing. Indeed, when compared with running using normal arm swing, we found that net metabolic power demand was 3, 9 and 13% greater for the BACK, CHEST and HEAD conditions, respectively (all Prunning without arm swing, subjects significantly increased the peak-to-peak amplitudes of both shoulder and pelvis rotation about the vertical axis, most likely a compensatory strategy to counterbalance the rotational angular momentum of the swinging legs. In conclusion, our findings support our general hypothesis that swinging the arms reduces the metabolic cost of human running. Our findings also demonstrate that arm swing minimizes torso rotation. We infer that actively swinging the arms provides both metabolic and biomechanical benefits during human running. © 2014. Published by The Company of Biologists Ltd.

The TIM Barrel Architecture Facilitated the Early Evolution of Protein-Mediated Metabolism.

Science.gov (United States)

Goldman, Aaron David; Beatty, Joshua T; Landweber, Laura F

2016-01-01

The triosephosphate isomerase (TIM) barrel protein fold is a structurally repetitive architecture that is present in approximately 10% of all enzymes. It is generally assumed that this ubiquity in modern proteomes reflects an essential historical role in early protein-mediated metabolism. Here, we provide quantitative and comparative analyses to support several hypotheses about the early importance of the TIM barrel architecture. An information theoretical analysis of protein structures supports the hypothesis that the TIM barrel architecture could arise more easily by duplication and recombination compared to other mixed α/β structures. We show that TIM barrel enzymes corresponding to the most taxonomically broad superfamilies also have the broadest range of functions, often aided by metal and nucleotide-derived cofactors that are thought to reflect an earlier stage of metabolic evolution. By comparison to other putatively ancient protein architectures, we find that the functional diversity of TIM barrel proteins cannot be explained simply by their antiquity. Instead, the breadth of TIM barrel functions can be explained, in part, by the incorporation of a broad range of cofactors, a trend that does not appear to be shared by proteins in general. These results support the hypothesis that the simple and functionally general TIM barrel architecture may have arisen early in the evolution of protein biosynthesis and provided an ideal scaffold to facilitate the metabolic transition from ribozymes, peptides, and geochemical catalysts to modern protein enzymes.

The "parallel pathway": a novel nutritional and metabolic approach to cancer patients.

Science.gov (United States)

Muscaritoli, Maurizio; Molfino, Alessio; Gioia, Gianfranco; Laviano, Alessandro; Rossi Fanelli, Filippo

2011-04-01

Cancer-associated malnutrition results from a deadly combination of anorexia, which leads to reduced food intake, and derangements of host metabolism inducing body weight loss, and hindering its reversal with nutrient supplementation. Cancer patients often experience both anorexia and weight loss, contributing to the onset of the clinical feature named as anorexia-cachexia syndrome. This condition has a negative impact upon patients' nutritional status. The pathogenesis of the anorexia-cachexia syndrome is multifactorial, and is related to: tumour-derived factors, host-derived factors inducing metabolic derangements, and side effects of anticancer therapies. In addition, the lack of awareness of cancer patients' nutritional issues and status by many oncologists, frequently results in progressive weight loss going undiagnosed until it becomes severe. The critical involvement of host inflammatory response in the development of weight loss, and, in particular, lean body mass depletion, limits the response to the provision of standard nutrition support. A novel nutritional and metabolic approach, named "parallel pathway", has been devised that may help maintain or improve nutritional status, and prevent or delay the onset of cancer cachexia. Such an approach may improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity and quality of life even in advanced disease stages. The "parallel pathway" implies a multiprofessional and multimodal approach aimed at ensuring early, appropriate and continuous nutritional and metabolic support to cancer patients in any phase of their cancer journey.

Metabolic rates are significantly lower in abyssal Holothuroidea than in shallow-water Holothuroidea

Science.gov (United States)

van Oevelen, Dick

2018-01-01

Recent analyses of metabolic rates in fishes, echinoderms, crustaceans and cephalopods have concluded that bathymetric declines in temperature- and mass-normalized metabolic rate do not result from resource-limitation (e.g. oxygen or food/chemical energy), decreasing temperature or increasing hydrostatic pressure. Instead, based on contrasting bathymetric patterns reported in the metabolic rates of visual and non-visual taxa, declining metabolic rate with depth is proposed to result from relaxation of selection for high locomotory capacity in visual predators as light diminishes. Here, we present metabolic rates of Holothuroidea, a non-visual benthic and benthopelagic echinoderm class, determined in situ at abyssal depths (greater than 4000 m depth). Mean temperature- and mass-normalized metabolic rate did not differ significantly between shallow-water (less than 200 m depth) and bathyal (200–4000 m depth) holothurians, but was significantly lower in abyssal (greater than 4000 m depth) holothurians than in shallow-water holothurians. These results support the dominance of the visual interactions hypothesis at bathyal depths, but indicate that ecological or evolutionary pressures other than biotic visual interactions contribute to bathymetric variation in holothurian metabolic rates. Multiple nonlinear regression assuming power or exponential models indicates that in situ hydrostatic pressure and/or food/chemical energy availability are responsible for variation in holothurian metabolic rates. Consequently, these results have implications for modelling deep-sea energetics and processes. PMID:29892403

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

Energy Technology Data Exchange (ETDEWEB)

Schulz, W.; Schmidt, M.

1986-12-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

International Nuclear Information System (INIS)

Schulz, W.; Schmidt, M.; Klinikum Bamberg

1986-01-01

Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early. (orig.) [de

Endocrine and metabolic characteristics in polycystic ovary syndrome

DEFF Research Database (Denmark)

Glintborg, Dorte

2016-01-01

of dyslipidemia, diabetes, and possibly cardiovascular disease. Patients diagnosed with PCOS therefore should be screened for elements in the metabolic syndrome including weight, waist, blood pressure, HbA1c, and lipid status. Our data supported that prolactin and HbA1c levels could be markers of cardiovascular......Hirsutism affects 5-25% women, and the condition is most often caused by polycystic ovary syndrome (PCOS). The initial evaluation of hirsute patients should include a thorough medical history, clinical evaluation, and standardized blood samples to diagnose the 5% hirsute patients with rare...... which subgroups of patients should be treated by their general practitioner and which patients should be referred for hospital and/or gynecological evaluation and treatment. Furthermore more data are needed to determine the optimal follow-up program regarding metabolic risk in different subgroups...

Bovine vaginal strain Kocuria kristinae and its characterization.

Science.gov (United States)

Styková, Eva; Nemcová, Radomíra; Gancarčíková, Soňa; Valocký, Igor; Lauková, Andrea

2016-05-01

Kocuria spp. are widely distributed in nature. They are Gram-positive, coagulase-negative, coccoid bacteria belonging to the family Micrococcaceae, suborder Micrococcineae, order Actinomycetales, class Actinobacteria. In general, limited knowledge exists concerning the properties associated with the representants of the genus Kocuria, Kocuria kristinae as well. Following our previous results, K. kristinae Kk2014 Biocenol(™) (CCM 8628) was isolated from vagina of a healthy cow. Its taxonomical allottation was confirmed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) identification system and phenotypic characteristics. Kk2014 strain showed strong adherence capability to the vaginal mucus, produced organic acids which can play a role in prevention of unsuitable contamination, and showed in vitro antagonistic/antimicrobial activity against strains Arcanobacterium pyogenes CCM 5753, Fusobacterium necrophorum CCM 5982, Streptococcus equi subsp. zooepidemicus CCM 7316, and Gardnerella vaginalis CCM 6221. Antimicrobial activity ranged from 100 to 200 AU/mL, up to 32 mm in size, respectively.

Absorption mechanism of whey-protein-delivered curcumin using Caco-2 cell monolayers.

Science.gov (United States)

Li, Ming; Cui, Jie; Ngadi, Michael O; Ma, Ying

2015-08-01

Curcumin (CCM) is a bioactive polyphenolic compound that suffers a low bioavailability because of its low water solubility. In this work β-lactoglobulin (β-Lg) and nanoemulsion were used as carriers to deliver curcumin. The pH stability of β-Lg-CCM was investigated. The digestion of β-Lg-CCM and the nanoemulsion was studied using an in vitro gastrointestinal model. The effect of different carriers on the permeability of curcumin was assessed using the Caco-2 cell monolayer model. The results revealed that the water solubility and the pH stability of curcumin significantly increased by binding with β-Lg. In SDS-PAGE experiments the β-Lg-CCM complex and nanoemulsion were found to be resistant to pepsin digestion but sensitive to trypsin. In the permeability experiment it was shown that the digested nanoemulsion and β-Lg-CCM improved significantly the permeation rate of curcumin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

Science.gov (United States)

Scholz, Gerhard H; Hanefeld, Markolf

2016-10-01

Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

Environmental and genetic influences on flight metabolic rate in the honey bee, Apis mellifera.

Science.gov (United States)

Harrison, Jon F; Fewell, Jennifer H

2002-10-01

Flying honey bees demonstrate highly variable metabolic rates. The lowest reported values (approximately 0.3 Wg(-1)) occur in tethered bees generating the minimum lift to support their body weight, free-flying 2-day old bees, winter bees, or bees flying at high air temperatures (45 degrees C). The highest values (approximately 0.8 Wg(-1)) occur in foragers that are heavily loaded or flying in low-density air. In different studies, flight metabolic rate has increased, decreased, or remained constant with air temperature. Current research collectively suggests that this variation occurs because flight metabolic rates decrease at thorax temperatures above or below 38 degrees C. At 30 degrees C, approximately 30% of colonial energy is spent during typical foraging, so variation in flight metabolic rate can strongly affect colony-level energy balance. Higher air temperatures tend to increase colonial net gain rates, efficiencies and honey storage rates due to lower metabolic rates during flight and in the hive. Variation in flight metabolism has a clear genetic basis. Different genetic strains of honey bees often differ in flight metabolic rate, and these differences in flight physiology can be correlated with foraging effort, suggesting a possible pathway for selection effects on flight metabolism.

Service Blueprint for Improving Clinical Guideline Adherence via Mobile Health Technology

OpenAIRE

Y. O'Connor; C. Heavin; S. O' Connor; J. Gallagher; J. Wu; J. O'Donoghue

2015-01-01

Background: To improve the delivery of paediatric healthcare in low resource settings, Community Health Workers (CHW) have been provided with a paper-based set of protocols known as Community Case Management (CCM). Yet research has shown that CHW adherence to CCM guidelines is poor, ultimately impacting health service delivery. Digitising the CCM guidelines via mobile technology is argued in extant literature to improve CHW adherence. However, little research exist which ...

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

Directory of Open Access Journals (Sweden)

Laura ePaixão

2015-10-01

Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

Science.gov (United States)

Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

2015-01-01

Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

The Adverse Effects of Alcohol on Vitamin A Metabolism

Directory of Open Access Journals (Sweden)

William S. Blaner

2012-05-01

Full Text Available The objective of this review is to explore the relationship between alcohol and the metabolism of the essential micronutrient, vitamin A; as well as the impact this interaction has on alcohol-induced disease in adults. Depleted hepatic vitamin A content has been reported in human alcoholics, an observation that has been confirmed in animal models of chronic alcohol consumption. Indeed, alcohol consumption has been associated with declines in hepatic levels of retinol (vitamin A, as well as retinyl ester and retinoic acid; collectively referred to as retinoids. Through the use of animal models, the complex interplay between alcohol metabolism and vitamin A homeostasis has been studied; the reviewed research supports the notion that chronic alcohol consumption precipitates a decline in hepatic retinoid levels through increased breakdown, as well as increased export to extra-hepatic tissues. While the precise biochemical mechanisms governing alcohol’s effect remain to be elucidated, its profound effect on hepatic retinoid status is irrefutable. In addition to a review of the literature related to studies on tissue retinoid levels and the metabolic interactions between alcohol and retinoids, the significance of altered hepatic retinoid metabolism in the context of alcoholic liver disease is also considered.

Anthelmintic metabolism in parasitic helminths: proteomic insights.

Science.gov (United States)

Brophy, Peter M; MacKintosh, Neil; Morphew, Russell M

2012-08-01

Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokinetics, and provide an integrated insight into both the cellular mechanisms underpinning response to anthelmintics and also the identification of biomarker panels for monitoring the development of anthelmintic resistance. To date, there have been limited attempts to include proteomics in anthelmintic metabolism studies. Optimisations of membrane, post-translational modification and interaction proteomic technologies in helminths are needed to especially study Phase I CYPs and Phase III ABC transporter pumps for anthelmintics and their metabolites.

Evidence for transgenerational metabolic programming in Drosophila

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Jessica L. Buescher

2013-09-01

Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon.

Metabolic Syndrome

Science.gov (United States)

Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

Fatty acids in energy metabolism of the central nervous system.

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Panov, Alexander; Orynbayeva, Zulfiya; Vavilin, Valentin; Lyakhovich, Vyacheslav

2014-01-01

In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

Diet and cognition: interplay between cell metabolism and neuronal plasticity.

Science.gov (United States)

Gomez-Pinilla, Fernando; Tyagi, Ethika

2013-11-01

To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

Metabolic syndrome and menopause

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Jouyandeh Zahra

2013-01-01

Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

Identifying organisational principles and management practices important to the quality of health care services for chronic conditions

DEFF Research Database (Denmark)

Frølich, Anne

2012-01-01

are limited, it is necessary to identify efficient methods to improve the quality of care. Comparing health care systems is a well-known method for identifying new knowledge regarding, for instance, organisational methods and principles. Kaiser Permanente (KP), an integrated health care delivery system...... in the U.S., is recognized as providing high-quality chronic care; to some extent, this is due to KP's implementation of the chronic care model (CCM). This model recommends a range of evidence-based management practices that support the implementation of evidence-based medicine. However, it is not clear...... which management practices in the CCM are most efficient and in what combinations. In addition, financial incentives and public reporting of performance are often considered effective at improving the quality of health care services, but this has not yet been definitively proved....

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

Science.gov (United States)

Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

2007-04-01

Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

Type I Interferon Responses Drive Intrahepatic T cells to Promote Metabolic Syndrome

DEFF Research Database (Denmark)

Ghazarian, Magar; Revelo, Xavier S; Nøhr, Mark K

2017-01-01

Obesity-related insulin resistance is driven by low-grade chronic inflammation of metabolic tissues. In the liver, non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance and systemic glucose dysregulation. However, the immunological factors supporting these proces...

The role of family nutritional support in Japanese patients with type 2 diabetes mellitus.

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Watanabe, Koin; Kurose, Takeshi; Kitatani, Naomi; Yabe, Daisuke; Hishizawa, Masahiro; Hyo, Takanori; Seino, Yutaka

2010-01-01

We investigated the role of family support in glycemic control by nutritional self-care behavior of Japanese patients with type 2 diabetes. One hundred twelve Japanese out-patients with type 2 diabetes were recruited for the study at Kansai Electric Power Hospital. Interviews were conducted and HbA1c and triglyceride levels were measured. HbA1c levels were significantly related to family nutritional support. Patients under 60 years old with family nutritional support showed significantly lower HbA1c than patients without family support (p1 week) showed similar outcomes in glycemic control. Patients who appreciate the support and follow the advice showed lower HbA1c (6.88 +/- 0.22%) than (7.43 +/- 0.23%) patients who appreciate the advice but sometimes feel emotional barriers. Family nutritional support is useful in improving metabolic outcome of diabetic patients. Self-care practice in disease management should be carefully adjusted to the family setting of type 2 diabetic patients. Emotional barriers to family support may affect the metabolic consequences, especially in the Japanese elderly.

Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism

Czech Academy of Sciences Publication Activity Database

Pavelka, Stanislav

2014-01-01

Roč. 63, Suppl.1 (2014), S133-S140 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 7AMB12SK158; GA ČR(CZ) GA304/08/0256 Institutional support: RVO:67985823 Keywords : enzyme * metabolism * radiometric assay * thyroid hormone Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.293, year: 2014

Antimicrobial and antioxidant activity of natural honeys of different origin

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Miartina Fikselová

2014-10-01

Full Text Available To examine the antimicrobial and antioxidant activity of 15 natural honeys, honey samples were collected from different locations of Slovakia, Poland and Serbia. For antimicrobial activity determination honey solutions were prepared at three concentrations: 50, 25 and 12.5 % (by mass per volume. The potential antimicrobial activity of  selected samples against four species of bacteria (Escherichia coli CCM 3988, Pseudomonas aeroginosa CCM 1960, Staphylococcus epidermis CCM 4418, Bacillus cereus CCM 2010 and two species of yeasts (Saccharomyces cerevisiae CCM 8191, Candida albicans CCM 8216 was studied using the disc diffusion method. After incubation, the zones of inhibition of the growth of the microorganisms around the disks were measured. The strongest antimicrobial activity was shown at honey samples of 50 % concentration against Escherichia coli, Pseudomonas aeroginosa and Staphylococcus epidermis. Against Saccharomyces cerevisae and Candida albicans very low (at 50 %, 25 % concentration or zero antifugal (at 12.5 % concentration activity was determined. From the results obtained it was shown the variable ability of honey samples to scavenge stable free radical DPPH. TEACDPPH values ranged between 0.1-1.0 mmol.kg-1. As the antioxidative best source buckwheat honey was manifested and the lowest antioxidant activity was shown at acacia honey.

Effect of Curcumin Supplementation on Physiological Fatigue and Physical Performance in Mice

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Wen-Ching Huang

2015-01-01

Full Text Available Curcumin (CCM is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 μg/mL by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN, and glucose and tissue damage markers such as aspartate transaminase (AST, alanine transaminase (ALT, and creatine kinase (CK. CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue.

Original communication: Basal metabolic rate in children with a solid tumor

NARCIS (Netherlands)

Broeder, den E.; Oeseburg, B.; Lippens, R.J.J.; Staveren, van W.A.; Sengers, R.C.A.; Hof, van 't M.A.; Tolboom, J.J.M.

2001-01-01

Objective: To study the level of and changes in basal metabolic rate (BMR) in children with a solid tumour at diagnosis and during treatment in order to provide a more accurate estimate of energy requirements for nutritional support. Design: An observational study. Setting: Tertiary care at the

OptFlux: an open-source software platform for in silico metabolic engineering.

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Rocha, Isabel; Maia, Paulo; Evangelista, Pedro; Vilaça, Paulo; Soares, Simão; Pinto, José P; Nielsen, Jens; Patil, Kiran R; Ferreira, Eugénio C; Rocha, Miguel

2010-04-19

Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications. OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph. The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.

Science.gov (United States)

Escobedo, Noelia; Oliver, Guillermo

2017-10-03

Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

Costing commodity and human resource needs for integrated community case management in thie differing community health strategies of Ethiopia, Kenya and Zambia.

Science.gov (United States)

Nefdt, Rory; Ribaira, Eric; Diallo, Khassoum

2014-10-01

To ensure correct and appropriate funding is available, there is a need to estimate resource needs for improved planning and implementation of integrated Community Case Management (iCCM). To compare and estimate costs for commodity and human resource needs for iCCM, based on treatment coverage rates, bottlenecks and national targets in Ethiopia, Kenya and Zambia from 2014 to 2016. Resource needs were estimated using Ministry of Health (MoH) targets fronm 2014 to 2016 for implementation of case management of pneumonia, diarrhea and malaria through iCCM based on epidemiological, demographic, economic, intervention coverage and other health system parameters. Bottleneck analysis adjusted cost estimates against system barriers. Ethiopia, Kenya and Zambia were chosen to compare differences in iCCM costs in different programmatic implementation landscapes. Coverage treatment rates through iCCM are lowest in Ethiopia, followed by Kenya and Zambia, but Ethiopia had the greatest increases between 2009 and 2012. Deployment of health extension workers (HEWs) in Ethiopia is more advanced compared to Kenya and Zambia, which have fewer equivalent cadres (called commu- nity health workers (CHWs)) covering a smaller proportion of the population. Between 2014 and 2016, the propor- tion of treatments through iCCM compared to health centres are set to increase from 30% to 81% in Ethiopia, 1% to 18% in Kenya and 3% to 22% in Zambia. The total estimated cost of iCCM for these three years are USD 75,531,376 for Ethiopia, USD 19,839,780 for Kenya and USD 33,667,742 for Zambia. Projected per capita expen- diture for 2016 is USD 0.28 for Ethiopia, USD 0.20 in Kenya and USD 0.98 in Zambia. Commodity costs for pneumonia and diarrhea were a small fraction of the total iCCM budget for all three countries (less than 3%), while around 80% of the costs related to human resources. Analysis of coverage, demography and epidemiology data improves estimates of fimding requirements for iCCM. Bottleneck

Supportive care in radiation oncology

International Nuclear Information System (INIS)

Rotman, M.; John, M.

1987-01-01

The radiation therapist, concerned with the disease process and all the technical intricacies of treatment, has usually not been involved in managing the supportive aspects of caring for the patient. Yet, of the team of medical specialists and allied health personnel required in oncology, the radiation therapist is the one most responsible for overseeing the total care of the cancer patient. At times this might include emotional support, prevention and correction of tissue dysfunction, augmentation of nutrition, metabolic and electrolyte regulation, rehabilitation, and vocational support. This chapter is a brief overview of a considerable volume of literature that has occupied the interest of a rather small group of physicians, nutritionists, and psychologists. The discussion highlights the special management problems of the normal-tissue effects of radiation, the related nutritional aspects of cancer care, and certain emotional and pathologic considerations

Inborn errors of metabolism: a clinical overview

Directory of Open Access Journals (Sweden)

Ana Maria Martins

1999-11-01

Full Text Available CONTEXT: Inborn errors of metabolism cause hereditary metabolic diseases (HMD and classically they result from the lack of activity of one or more specific enzymes or defects in the transportation of proteins. OBJECTIVES: A clinical review of inborn errors of metabolism (IEM to give a practical approach to the physician with figures and tables to help in understanding the more common groups of these disorders. DATA SOURCE: A systematic review of the clinical and biochemical basis of IEM in the literature, especially considering the last ten years and a classic textbook (Scriver CR et al, 1995. SELECTION OF STUDIES: A selection of 108 references about IEM by experts in the subject was made. Clinical cases are presented with the peculiar symptoms of various diseases. DATA SYNTHESIS: IEM are frequently misdiagnosed because the general practitioner, or pediatrician in the neonatal or intensive care units, does not think about this diagnosis until the more common cause have been ruled out. This review includes inheritance patterns and clinical and laboratory findings of the more common IEM diseases within a clinical classification that give a general idea about these disorders. A summary of treatment types for metabolic inherited diseases is given. CONCLUSIONS: IEM are not rare diseases, unlike previous thinking about them, and IEM patients form part of the clientele in emergency rooms at general hospitals and in intensive care units. They are also to be found in neurological, pediatric, obstetrics, surgical and psychiatric clinics seeking diagnoses, prognoses and therapeutic or supportive treatment.

[Gut microbiota and immune crosstalk in metabolic disease].

Science.gov (United States)

Burcelin, Rémy

2017-01-01

, and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, which induces inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities. © Société de Biologie, 2017.

Weight loss experiences of obese perimenopausal women with metabolic syndrome.

Science.gov (United States)

Su, Mei-Chen; Lin, Hung-Ru; Chu, Nain-Feng; Huang, Chih-Hsung; Tsao, Lee-Ing

2015-07-01

To develop a descriptive theory for the weight loss experiences of obese perimenopausal women with metabolic syndrome. Obesity and metabolic syndrome both pose a threat to the health of perimenopausal women; therefore, understanding perimenopausal women's subjective feelings and experiences is beneficial to establishing effective prevention strategies. However, studies have rarely explored these relevant experiences. A qualitative study using the grounded theory method to establish a descriptive theory. Eighteen obese perimenopausal women with metabolic syndrome aged 45-60 years participated in comprehensive interviews. 'Crossing the gaps to making life modifications' was the core category, and 'the awareness of weight gain and health alarm' was the antecedent condition. In the weight loss experience, the following three interaction categories were identified: (1) 'experiencing bad feelings,' (2) 'encountering obstacles' and (3) 'making efforts to transition to a new life.' Some women adhered to new life habits through perceiving social support and by using self-incentives. Finally, women enjoyed and mastered self-monitoring of their health in their new life, and practiced new changes as part of their life. However, some participants felt that making changes to their life was too time-consuming. Therefore, these women chose to live with their abnormal health without making changes. Obese perimenopausal women with metabolic syndrome experienced various gaps in their weight loss process. Although they struggled with many obstacles, these women were able to learn from their experiences and face their health challenges. These findings can guide healthcare professionals to provide appropriate interventions to understand the hidden health problems of this particular group of women. Healthcare professionals should develop a set of plans by which women receive a complete weight loss program and support from professionals and family. © 2015 John Wiley & Sons Ltd.

A New Water-Soluble Nanomicelle Formed through Self-Assembly of Pectin-Curcumin Conjugates: Preparation, Characterization, and Anticancer Activity Evaluation.

Science.gov (United States)

Bai, Feng; Diao, Jiajing; Wang, Ying; Sun, Shixin; Zhang, Hongmei; Liu, Yunyun; Wang, Yanqing; Cao, Jian

2017-08-16

Curcumin is a dominating active component of Curcuma longa and has been studied widely because of its prominent biological activities. The extremely low aqueous solubility, stability, and bioavailability of curcumin limit its application in the field of medicine. In this study, we developed pectin-curcumin (PEC-CCM) conjugates that could self-assemble water-soluble nanomicelles in aqueous solution. The structure of PEC-CCM conjugates was characterized by ultraviolet-visible spectra, fluorescence spectra, Fourier transform infrared spectroscopy, and 1 H nuclear magnetic resonance spectroscopy. The thermal property of PEC-CCM conjugates was investigated by thermogravimetric analysis. It was found that PEC-CCM conjugates had formed nanomicelles in aqueous medium via self-assembly. These nanomicelles were observed as small spheres or ellipsoids and aggregated with a size range of 70-190 nm by transmission electron microscopy analysis. In a solution of nanomicelles, the stability of curcumin was improved, and its antioxidant property was preserved. The anticancer activity of PEC-CCM conjugates was quantified by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay using a hepatic cancer cell line (HepG2), a breast cancer cell line (MCF-7), a cervical cancer cell line (HeLa), and a human normal kidney cell line (293A). It was found that the curcumin of PEC-CCM conjugates had a more significant inhibitory effect on cancer cells and was less cytotoxic to normal cells than free curcumin was. PEC-CCM conjugates have great potential for some food and pharmaceutical applications.

MCT4 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies

Directory of Open Access Journals (Sweden)

GuemHee Baek

2014-12-01

Full Text Available KRAS mutation, which occurs in ∼95% of pancreatic ductal adenocarcinoma (PDA, has been shown to program tumor metabolism. MCT4 is highly upregulated in a subset of PDA with a glycolytic gene expression program and poor survival. Models with high levels of MCT4 preferentially employ glycolytic metabolism. Selectively in such “addicted” models, MCT4 attenuation compromised glycolytic flux with compensatory induction of oxidative phosphorylation and scavenging of metabolites by macropinocytosis and autophagy. In spite of these adaptations, MCT4 depletion induced cell death characterized by elevated reactive oxygen species and metabolic crisis. Cell death induced by MCT4-depletion was augmented by inhibition of compensatory pathways. In xenograft models, MCT4 had a significant impact on tumor metabolism and was required for rapid tumor growth. Together, these findings illustrate the metabolic diversity of PDA described by MCT4, delineate pathways through which this lactate transporter supports cancer growth, and demonstrate that PDA can be rationally targeted based on metabolic addictions.

Exogenous Classic Phytohormones Have Limited Regulatory Effects on Fructan and Primary Carbohydrate Metabolism in Perennial Ryegrass (Lolium perenne L.)

Czech Academy of Sciences Publication Activity Database

Gasperl, A.; Morvan-Bertrand, A.; Prud'homme, M. P.; van der Graaff, E.; Roitsch, Thomas

2016-01-01

Roč. 6, jan (2016), s. 1251 ISSN 1664-462X R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : enzymatic activity * fructan exohydrolase * fructan metabolism * fructosyltransferase * perennial ryegrass * phytohormones * primary carbohydrate metabolism Subject RIV: ED - Physiology Impact factor: 4.298, year: 2016

Metabolic regulation of inflammation.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

2017-05-01

Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

Effects of Space Flight, Clinorotation, and Centrifugation on the Growth and Metabolism of Escherichia Coli

Science.gov (United States)

Brown, Robert B.

1999-01-01

Previous experiments have shown that space flight stimulates bacterial growth and metabolism. An explanation for these results is proposed, which may eventually lead to improved terrestrial pharmaceutical production efficiency. It is hypothesized that inertial acceleration affects bacterial growth and metabolism by altering the transport phenomena in the cells external fluid environment. It is believed that this occurs indirectly through changes in the sedimentation rate acting on the bacteria and buoyancy-driven convection acting on their excreted by-products. Experiments over a broad range of accelerations consistently supported this theory. Experiments at I g indicated that higher concentrations of excreted by products surrounding bacterial cells result in a shorter lag phase. Nineteen additional experiments simulated 0 g and 0.5 g using a clinostat, and achieved 50 g, 180 g, and 400 g using a centrifuge. These experiments showed that final cell density is inversely related to the level of acceleration. The experiments also consistently showed that acceleration affects the length of the lag phase in a non-monotonic, yet predictable, manner. Additional data indicated that E. coli metabolize glucose less efficiently at hypergravity, and more efficiently at hypogravity. A space-flight experiment was also performed. Samples on orbit had a statistically significant higher final cell density and more efficient metabolism than did ground controls. These results. which were similar to simulations of 0 g using a clinostat, support the theory that gravity only affects bacterial growth and metabolism indirectly, through changes in the bacteria's fluid environment.

Metabolic Control of Redox and Redox Control of Metabolism in Plants

Science.gov (United States)

Fernie, Alisdair R.

2014-01-01

Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

Blocking hexose entry into glycolysis activates alternative metabolic conversion of these sugars and upregulates pentose metabolism in Aspergillus nidulans

Energy Technology Data Exchange (ETDEWEB)

Khosravi, Claire; Battaglia, Evy; Kun, Roland S.; Dalhuijsen, Sacha; Visser, Jaap; Aguilar-Pontes, Maria V.; Zhou, Miamiao; Heyman, Heino M.; Kim, Young-Mo; Baker, Scott E.; de Vries, Ronald P.

2018-03-22

Background: Plant biomass is the most abundant carbon source for many fungal species. In the biobased industry fungi are used to produce lignocellulolytic enzymes to degrade agricultural waste biomass. Here we evaluated if it would be possible to create an Aspergillus nidulans strain that releases but does not metabolize hexoses from plant biomass. For this purpose, metabolic mutants were generated that were impaired in glycolysis, by using hexokinase (hxkA) and glucokinase (glkA) negative strains. To prevent repression of enzyme production due to the hexose accumulation, strains were generated that combined these mutations with a deletion in creA, the repressor involved in regulating preferential use of different carbon catabolic pathways. Results: Phenotypic analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran. However, hexoses did not accumulate during growth of the mutants on wheat bran, suggesting that glucose metabolism is re-routed towards alternative carbon catabolic pathways. The creAΔ4 mutation in combination with preventing initial phosphorylation in glycolysis resulted in better growth than the hxkA/glkA mutant and an increased expression of pentose catabolic and pentose phosphate pathway genes. This indicates that the reduced ability to use hexoses as carbon sources created a shift towards the pentose fraction of wheat bran as a major carbon source to support growth. Conclusion: Blocking the direct entry of hexoses to glycolysis activates alternative metabolic conversion of these sugars in A. nidulans during growth on plant biomass, but also upregulates conversion of other sugars, such as pentoses.

Treatment of metabolic syndrome.

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Wagh, Arati; Stone, Neil J

2004-03-01

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin

Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling.

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Madji Hounoum, Blandine; Mavel, Sylvie; Coque, Emmanuelle; Patin, Franck; Vourc'h, Patrick; Marouillat, Sylviane; Nadal-Desbarats, Lydie; Emond, Patrick; Corcia, Philippe; Andres, Christian R; Raoul, Cédric; Blasco, Hélène

2017-04-01

The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605. © 2017 Wiley Periodicals, Inc.

Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk

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Hoeft, B.; Linseisen, J.; Beckmann, L.

2010-01-01

as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred......Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes...... variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk....

Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat.

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Park, Thomas J; Reznick, Jane; Peterson, Bethany L; Blass, Gregory; Omerbašić, Damir; Bennett, Nigel C; Kuich, P Henning J L; Zasada, Christin; Browe, Brigitte M; Hamann, Wiebke; Applegate, Daniel T; Radke, Michael H; Kosten, Tetiana; Lutermann, Heike; Gavaghan, Victoria; Eigenbrod, Ole; Bégay, Valérie; Amoroso, Vince G; Govind, Vidya; Minshall, Richard D; Smith, Ewan St J; Larson, John; Gotthardt, Michael; Kempa, Stefan; Lewin, Gary R

2017-04-21

The African naked mole-rat's ( Heterocephalus glaber ) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease. Copyright © 2017, American Association for the Advancement of Science.

Does circadian disruption play a role in the metabolic-hormonal link to delayed lactogenesis II?

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Manjie eFu

2015-02-01

Full Text Available Breastfeeding improves maternal and child health. The American Academy of Pediatrics recommends exclusive breastfeeding for six months, with continued breastfeeding for at least one year. However, in the US, only 18.8% of infants are exclusively breastfed until six months of age. For mothers who initiate breastfeeding, the early postpartum period sets the stage for sustained breastfeeding. Mothers who experience breastfeeding problems in the early postpartum period are more likely to discontinue breastfeeding within two weeks. A major risk factor for shorter breastfeeding duration is delayed lactogenesis II (i.e. onset of milk coming in more than 72 h postpartum. Recent studies report a metabolic-hormonal link to delayed lactogenesis II. This is not surprising because around the time of birth the mother’s entire metabolism changes to direct nutrients to mammary glands. Circadian and metabolic systems are closely linked, and our rodent studies suggest circadian clocks coordinate hormonal and metabolic changes to support lactation. Molecular and environmental disruption of the circadian system decreases a dam’s ability to initiate lactation and negatively impacts milk production. Circadian and metabolic systems evolved to be functional and adaptive when lifestyles and environmental exposures were quite different from modern times. We now have artificial lights, longer work days, and increases in shift work. Disruption in the circadian system due to shift work, jet lag, sleep disorders and other modern life style choices are associated with metabolic disorders, obesity, and impaired reproduction. We hypothesize delayed lactogenesis II is related to disruption of the mother’s circadian system. Here we review literature that supports this hypothesis, and describe interventions that may help to increase breastfeeding success.

Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics.

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Chicco, Adam J; Le, Catherine H; Gnaiger, Erich; Dreyer, Hans C; Muyskens, Jonathan B; D'Alessandro, Angelo; Nemkov, Travis; Hocker, Austin D; Prenni, Jessica E; Wolfe, Lisa M; Sindt, Nathan M; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

2018-05-04

Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia down-regulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose toward pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity in vivo Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Altered metabolism in cancer

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Locasale Jason W

2010-06-01

Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

Food composition influences metabolism, heart rate and organ growth during digestion in Python regius.

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Henriksen, Poul Secher; Enok, Sanne; Overgaard, Johannes; Wang, Tobias

2015-05-01

Digestion in pythons is associated with a large increase in oxygen consumption (SDA), increased cardiac output and growth in visceral organs assisting in digestion. The processes leading to the large postprandial rise in metabolism in snakes is subject to opposing views. Gastric work, protein synthesis and organ growth have each been speculated to be major contributors to the SDA. To investigate the role of food composition on SDA, heart rate (HR) and organ growth, 48 ball pythons (Python regius) were fed meals of either fat, glucose, protein or protein combined with carbonate. Our study shows that protein, in the absence or presence of carbonate causes a large SDA response, while glucose caused a significantly smaller SDA response and digestion of fat failed to affect metabolism. Addition of carbonate to the diet to stimulate gastric acid secretion did not increase the SDA response. These results support protein synthesis as a major contributor to the SDA response and show that increased gastric acid secretion occurs at a low metabolic cost. The increase in metabolism was supported by tachycardia caused by altered autonomic regulation as well as an increased non-adrenergic, non-cholinergic (NANC) tone in response to all diets, except for the lipid meal. Organ growth only occurred in the small intestine and liver in snakes fed on a high protein diet. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolic Risk Profile and Cancer in Korean Men and Women.

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Ko, Seulki; Yoon, Seok-Jun; Kim, Dongwoo; Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

2016-05-01

Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

Metabolic and demographic feedbacks shape the emergent spatial structure and function of microbial communities.

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Sylvie Estrela

Full Text Available Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships, and species spatial organization (structural relationships are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource is traded for detoxification (service and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition, and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies.

Impact of novel palmitoylated prolactin-eleasing peptide analogs on metabolic changes in mice with diet-induced obesity

Czech Academy of Sciences Publication Activity Database

Pražienková, V.; Holubová, M.; Pelantová, H.; Bugáňová, M.; Pirník, Z.; Mikulášková, Barbora; Popelová, A.; Blechová, M.; Haluzík, M.; Železná, B.; Kuzma, M.; Kuneš, Jaroslav; Maletínská, L.

2017-01-01

Roč. 12, č. 8 (2017), č. článku e0183449. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : food intake regulation * peroxisome proliferation * lipidized analogs Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes , hormones) Impact factor: 2.806, year: 2016

Secondary psychosis induced by metabolic disorders

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Olivier eBonnot

2015-05-01

Full Text Available Metabolic disorders are not well recognized by psychiatrists as a possible source of secondary psychoses. Inborn errors of metabolism (IEMs are not frequent. Although, their prompt diagnosis may lead to suitable treatments. IEMs are well known to paediatricians, in particular for their most serious forms, having an early expression most of the time. Recent years discoveries have unveiled later expression forms, and sometimes, very discreet first physical signs. There is a growing body of evidence that supports the hypothesis that IEMs can manifest as atypical psychiatric symptoms, even in the absence of clear neurological symptoms. In the present review, we propose a detailed overview at schizophrenia-like and autism-like symptoms that can lead practitioners to bear in mind an IEM. Other psychiatric manifestations are also found, as behavioral., cognitive, learning and mood disorders. However, they are less frequent. Ensuring an accurate IEM diagnosis, in front of these psychiatric symptoms should be a priority, in order to grant suitable and valuable treatment for these pathologies.

Complex Correlation Measure: a novel descriptor for Poincaré plot

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Gubbi Jayavardhana

2009-08-01

Full Text Available Abstract Background Poincaré plot is one of the important techniques used for visually representing the heart rate variability. It is valuable due to its ability to display nonlinear aspects of the data sequence. However, the problem lies in capturing temporal information of the plot quantitatively. The standard descriptors used in quantifying the Poincaré plot (SD1, SD2 measure the gross variability of the time series data. Determination of advanced methods for capturing temporal properties pose a significant challenge. In this paper, we propose a novel descriptor "Complex Correlation Measure (CCM" to quantify the temporal aspect of the Poincaré plot. In contrast to SD1 and SD2, the CCM incorporates point-to-point variation of the signal. Methods First, we have derived expressions for CCM. Then the sensitivity of descriptors has been shown by measuring all descriptors before and after surrogation of the signal. For each case study, lag-1 Poincaré plots were constructed for three groups of subjects (Arrhythmia, Congestive Heart Failure (CHF and those with Normal Sinus Rhythm (NSR, and the new measure CCM was computed along with SD1 and SD2. ANOVA analysis distribution was used to define the level of significance of mean and variance of SD1, SD2 and CCM for different groups of subjects. Results CCM is defined based on the autocorrelation at different lags of the time series, hence giving an in depth measurement of the correlation structure of the Poincaré plot. A surrogate analysis was performed, and the sensitivity of the proposed descriptor was found to be higher as compared to the standard descriptors. Two case studies were conducted for recognizing arrhythmia and congestive heart failure (CHF subjects from those with NSR, using the Physionet database and demonstrated the usefulness of the proposed descriptors in biomedical applications. CCM was found to be a more significant (p = 6.28E-18 parameter than SD1 and SD2 in discriminating

Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice

International Nuclear Information System (INIS)

Siddiqui, Rafat A; Harvey, Kevin A; Walker, Candace; Altenburg, Jeffrey; Xu, Zhidong; Terry, Colin; Camarillo, Ignacio; Jones-Hall, Yava; Mariash, Cary

2013-01-01

The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice. We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean ± SD and analyzed with one-way ANOVA and Tukey’s post hoc procedure. Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of “PAM50” genes in the SK-BR-3 cell line from an ER - /Her-2 + to that resembling a “normal-like” phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin. The SK-BR-3 cells and DMBA-induced tumors, both with an ER - and Her-2 + phenotype, were affected by the

Network analysis of metabolic enzyme evolution in Escherichia coli

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Kraulis Per

2004-02-01

Full Text Available Abstract Background The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc. Results Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1. Conclusions The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

Deconstructing Black Swans: An Introductory Approach to Inherited Metabolic Disorders in the Neonate.

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Mew, Nicholas Ah; Viall, Sarah; Kirmse, Brian; Chapman, Kimberly A

2015-08-01

Inherited metabolic disorders (IMDs) are individually rare but collectively common disorders that frequently require rapid or urgent therapy. This article provides a generalized approach to IMDs, as well as some investigations and safe therapies that may be initiated pending the metabolic consult. An overview of the research supporting management strategies is provided. In addition, the newborn metabolic screen is reviewed. Caring for infants with IMDs can seem difficult because each of the types is rarely seen; however, collectively the management can be seen as similar. When an IMD is suspected, a metabolic specialist should be consulted for expert advice regarding appropriate laboratory investigations and management. Because rapid intervention of IMDs before the onset of symptoms may prevent future irreversible sequelae, each abnormal newborn screen must be addressed promptly. Management can be difficult. Research in this area is limited and can be difficult without multisite coordination since sample sizes of any significance are difficult to achieve.

NPAS2 and PER2 are linked to risk factors of the metabolic syndrome

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Aromaa Arpo

2009-05-01

Full Text Available Abstract Background Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well. Seasonality elevates the risk for metabolic syndrome, and evidence suggests that disruption of the clockwork can lead to alterations in metabolism. Our aim was to analyze whether circadian clock polymorphisms contribute to seasonal variations in behavior and to the metabolic syndrome. Methods We genotyped 39 single-nucleotide polymorphisms (SNP from 19 genes which were either canonical circadian clock genes or genes related to the circadian clockwork from 517 individuals drawn from a nationwide population-based sample. Associations between these SNPs and seasonality, metabolic syndrome and its risk factors were analyzed using regression analysis. The p-values were corrected for multiple testing. Results Our findings link circadian gene variants to the risk factors of the metabolic syndrome, since Npas2 was associated with hypertension (P-value corrected for multiple testing = 0.0024 and Per2 was associated with high fasting blood glucose (P-value corrected for multiple testing = 0.049. Conclusion Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist.

Astrocyte glycogenolysis is triggered by store-operated calcium entry and provides metabolic energy for cellular calcium homeostasis

DEFF Research Database (Denmark)

Müller, Margit S; Fox, Rebecca; Schousboe, Arne

2014-01-01

Astrocytic glycogen, the only storage form of glucose in the brain, has been shown to play a fundamental role in supporting learning and memory, an effect achieved by providing metabolic support for neurons. We have examined the interplay between glycogenolysis and the bioenergetics of astrocytic...

Mycobacterium tuberculosis Metabolism

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