A Unique Role of Endogenous Visual-Spatial Attention in Rapid Processing of Multiple Targets

ERIC Educational Resources Information Center

Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru

2011-01-01

Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions).…

Apple fruit responses following exposure to nitric oxide

USDA-ARS?s Scientific Manuscript database

Exogenous nitric oxide (.NO) applied as gas or generated from .NO releasing compounds has physiological activity in cut apple fruit tissues. Studies were conducted to characterize .NO production by whole fruit as well as to assess responses of whole fruit to exogenous .NO. .NO and ethylene product...

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Exogenic and endogenic albedo and color patterns on Europa

NASA Technical Reports Server (NTRS)

Mcewen, A. S.

1986-01-01

New global and high-resolution multispectral mosaics of Europa have been produced from the Voyager imaging data. Photometric normalizations are based on multiple-image techniques that explicitly account for intrinsic albedo variations through pixel-by-pixel solutions. The exogenic color and albedo pattern on Europa is described by a second-order function of the cosine of the angular distance from the apex of orbital motion. On the basis of this second-order function and of color trends that are different on the leading and trailing hemispheres, the exogenic pattern is interpreted as being due to equilibrium between two dominant processes: (1) impact gardening and (2) magnetospheric interactions, including sulfur-ion implantation and sputtering redistribution. Removal of the model exogenic pattern in the mosaics reveals the endogenic variations, consisting of only two major units: darker (redder) and bright materials. Therefore Europa's visual spectral reflectivity is simple, having one continuous exogenic pattern and two discrete endogenic units.

Exogenous Social Identity Cues Differentially Affect the Dynamic Tracking of Individual Target Faces

ERIC Educational Resources Information Center

Allen, Roy; Gabbert, Fiona

2013-01-01

We report on an experiment to investigate the top-down effect of exogenous social identity cues on a multiple-identity tracking task, a paradigm well suited to investigate the processes of binding identity to spatial locations. Here we simulated an eyewitness event in which dynamic targets, all to be tracked with equal effort, were identified from…

Exogenous Attention Enables Perceptual Learning

PubMed Central

Szpiro, Sarit F. A.; Carrasco, Marisa

2015-01-01

Practice can improve visual perception, and these improvements are considered to be a form of brain plasticity. Training-induced learning is time-consuming and requires hundreds of trials across multiple days. The process of learning acquisition is understudied. Can learning acquisition be potentiated by manipulating visual attentional cues? We developed a protocol in which we used task-irrelevant cues for between-groups manipulation of attention during training. We found that training with exogenous attention can enable the acquisition of learning. Remarkably, this learning was maintained even when observers were subsequently tested under neutral conditions, which indicates that a change in perception was involved. Our study is the first to isolate the effects of exogenous attention and to demonstrate its efficacy to enable learning. We propose that exogenous attention boosts perceptual learning by enhancing stimulus encoding. PMID:26502745

Diagnostic utility of dermatoscopy in hydroquinone-induced exogenous ochronosis.

PubMed

Mishra, Sunil N; Dhurat, Rachita S; Deshpande, Deepal J; Nayak, Chitra S

2013-04-01

  Hydroquinone is the preferred topical bleaching agent used in the treatment of melasma. The adverse effects of its chronic use are confetti-like depigmentation and exogenous ochronosis. Exogenous ochronosis manifests clinically with gray-brown or blue-black hyperpigmentation, as well as pinpoint hyperchromic caviar-like papules over the malar region. Dermatoscopic findings of ochronosis are unique and point towards a clue for its diagnosis.   Three cases of suspected hydroquinone-induced exogenous ochronosis while treating melasma were subjected to dermatoscopy and histopathology studies.   Dermatoscopy in the areas of caviar-like hyperpigmentation revealed accentuation of the normal pseudo-rete of the facial skin with amorphous densely-pigmented structures obliterating some follicular opening and multiple thin, short arciform structures. On histopathological examination, curved ochre-colored structures, 'banana-shaped' fibers, were seen in the dermis of all patients.   Exogenous ochronosis is difficult to treat. Dermatologists should be able to differentiate it from melasma and immediately discontinue hydroquinone. Exogenous ochronosis has characteristic features on dermatoscopy which may obviate the need for an invasive procedure of biopsy for its diagnosis. © 2012 The International Society of Dermatology.

Heme acquisition in the parasitic filarial nematode Brugia malayi.

PubMed

Luck, Ashley N; Yuan, Xiaojing; Voronin, Denis; Slatko, Barton E; Hamza, Iqbal; Foster, Jeremy M

2016-10-01

Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter B. malayi HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3-6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi. © The Author(s).

Heme acquisition in the parasitic filarial nematode Brugia malayi

PubMed Central

Luck, Ashley N.; Yuan, Xiaojing; Voronin, Denis; Slatko, Barton E.; Hamza, Iqbal; Foster, Jeremy M.

2016-01-01

Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter B. malayi HRG-1 (BmHRG-1) is indeed functional in B. malayi. In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non–heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3–6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.—Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi. PMID:27363426

Exogenous Attention Enables Perceptual Learning.

PubMed

Szpiro, Sarit F A; Carrasco, Marisa

2015-12-01

Practice can improve visual perception, and these improvements are considered to be a form of brain plasticity. Training-induced learning is time-consuming and requires hundreds of trials across multiple days. The process of learning acquisition is understudied. Can learning acquisition be potentiated by manipulating visual attentional cues? We developed a protocol in which we used task-irrelevant cues for between-groups manipulation of attention during training. We found that training with exogenous attention can enable the acquisition of learning. Remarkably, this learning was maintained even when observers were subsequently tested under neutral conditions, which indicates that a change in perception was involved. Our study is the first to isolate the effects of exogenous attention and to demonstrate its efficacy to enable learning. We propose that exogenous attention boosts perceptual learning by enhancing stimulus encoding. © The Author(s) 2015.

Methods and materials for the production of L-lactic acid in yeast

DOEpatents

Hause, Ben [Jordan, MN; Rajgarhia, Vineet [Minnetonka, MN; Suominen, Pirkko [Maple Grove, MN

2009-05-19

Recombinant yeast are provided having, in one aspect, multiple exogenous LDH genes integrated into the genome, while leaving native PDC genes intact. In a second aspect, recombinant yeast are provided having an exogenous LDH gene integrated into its genome at the locus of a native PDC gene, with deletion of the native PDC gene. The recombinant yeast are useful in fermentation process for producing lactic acid.

Elongator Plays a Positive Role in Exogenous NAD-Induced Defense Responses in Arabidopsis.

PubMed

An, Chuanfu; Ding, Yezhang; Zhang, Xudong; Wang, Chenggang; Mou, Zhonglin

2016-05-01

Extracellular NAD is emerging as an important signal molecule in animal cells, but its role in plants has not been well-established. Although it has been shown that exogenous NAD(+) activates defense responses in Arabidopsis, components in the exogenous NAD(+)-activated defense pathway remain to be fully discovered. In a genetic screen for mutants insensitive to exogenous NAD(+) (ien), we isolated a mutant named ien2. Map-based cloning revealed that IEN2 encodes ELONGATA3 (ELO3)/AtELP3, a subunit of the Arabidopsis Elongator complex, which functions in multiple biological processes, including histone modification, DNA (de)methylation, and transfer RNA modification. Mutations in the ELO3/AtELP3 gene compromise exogenous NAD(+)-induced expression of pathogenesis-related (PR) genes and resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326, and transgenic expression of the coding region of ELO3/AtELP3 in elo3/Atelp3 restores NAD(+) responsiveness to the mutant plants, demonstrating that ELO3/AtELP3 is required for exogenous NAD(+)-induced defense responses. Furthermore, mutations in genes encoding the other five Arabidopsis Elongator subunits (ELO2/AtELP1, AtELP2, ELO1/AtELP4, AtELP5, and AtELP6) also compromise exogenous NAD(+)-induced PR gene expression and resistance to P. syringae pv. maculicola ES4326. These results indicate that the Elongator complex functions as a whole in exogenous NAD(+)-activated defense signaling in Arabidopsis.

MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

PubMed

Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

2015-07-01

Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

Anaerobic conditions improve germination of a gibberellic acid deficient rice

NASA Technical Reports Server (NTRS)

Frantz, Jonathan M.; Bugbee, Bruce

2002-01-01

Dwarf plants are useful in research because multiple plants can be grown in a small area. Rice (Oryza sativa L.) is especially important since its relatively simple genome has recently been sequenced. We are characterizing a gibberellic acid (GA) mutant of rice (japonica cv 'Shiokari,' line N-71) that is extremely dwarf (20 cm tall). Unfortunately, this GA mutation is associated with poor germination (70%) under aerobic conditions. Neither exogenous GA nor a dormancy-breaking heat treatment improved germination. However, 95% germination was achieved by germinating the seeds anaerobically, either in a pure N2 environment or submerged in unstirred tap water. The anaerobic conditions appear to break a mild post-harvest dormancy in this rice cultivar. Copyright 2002 Crop Science Society of America.

Anaerobic conditions improve germination of a gibberellic acid deficient rice.

PubMed

Frantz, Jonathan M; Bugbee, Bruce

2002-01-01

Dwarf plants are useful in research because multiple plants can be grown in a small area. Rice (Oryza sativa L.) is especially important since its relatively simple genome has recently been sequenced. We are characterizing a gibberellic acid (GA) mutant of rice (japonica cv 'Shiokari,' line N-71) that is extremely dwarf (20 cm tall). Unfortunately, this GA mutation is associated with poor germination (70%) under aerobic conditions. Neither exogenous GA nor a dormancy-breaking heat treatment improved germination. However, 95% germination was achieved by germinating the seeds anaerobically, either in a pure N2 environment or submerged in unstirred tap water. The anaerobic conditions appear to break a mild post-harvest dormancy in this rice cultivar. Copyright 2002 Crop Science Society of America.

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation.

PubMed

Imai, Jun; Otani, Mayu; Sakai, Takahiro; Hatta, Shinichi

2017-08-21

Dendritic cells (DCs) are highly capable of processing and presenting internalized exogenous antigens upon major histocompatibility class (MHC) I molecules also known as cross-presentation (CP). CP plays an important role not only in the stimulation of naïve CD8 + T cells and memory CD8 + T cells for infectious and tumor immunity but also in the inactivation of self-acting naïve T cells by T cell anergy or T cell deletion. Although the critical molecular mechanism of CP remains to be elucidated, accumulating evidence indicates that exogenous antigens are processed through endoplasmic reticulum-associated degradation (ERAD) after export from non-classical endocytic compartments. Until recently, characterizations of these endocytic compartments were limited because there were no specific molecular markers other than exogenous antigens. The method described here is a new vesicle isolation protocol, which allows for the purification of these endocytic compartments. Using this purified microsome, we reconstituted the ERAD-like transport, ubiquitination, and processing of the exogenous antigen in vitro, suggesting that the ubiquitin-proteasome system processed the exogenous antigen after export from this cellular compartment. This protocol can be further applied to other cell types to clarify the molecular mechanism of CP.

Enhancement of bioelectricity generation via heterologous expression of IrrE in Pseudomonas aeruginosa-inoculated MFCs.

PubMed

Luo, Jianmei; Wang, Tingting; Li, Xiao; Yang, Yanan; Zhou, Minghua; Li, Ming; Yan, Zhongli

2018-05-30

Low electricity power output (EPT) is still the main bottleneck limited the industrial application of microbial fuel cells (MFCs). Herein, EPT enhancement by introducing an exogenous global regulator IrrE derived from Deinococcus radiodurans into electrochemically active bacteria (EAB) was explored using Pseudomonas aeruginosa PAO1 as a model strain, achieving a power density 71% higher than that of the control strain. Moreover, IrrE-expressing strain exhibited a remarkable increase in the total amount of electron shuttles (majorly phenazines compounds) and a little decrease in internal resistance, which should underlie the enhancement in extracellular electron transfer (EET) efficiency and EPT. Strikingly, IrrE significantly affected substrate utilization profiling, improved cell growth characterization and cell tolerance to various stresses. Further quantitative RT-PCR analysis revealed that IrrE led to many differentially expressed genes, which were responsible for phenazines core biosynthesis, biofilm formation, QS systems, transcriptional regulation, glucose metabolism and general stress response. The results substantiated that targeting cellular regulatory network by the introduction of exogenous global regulators could be a facile and promising approach for the enhancement of bioelectricity generation and cell multiple phenotypes, and thus would be of great potential application in the practical MFCs. Copyright © 2018 Elsevier B.V. All rights reserved.

Dynamics of tuberculosis transmission with exogenous reinfections and endogenous reactivation

NASA Astrophysics Data System (ADS)

Khajanchi, Subhas; Das, Dhiraj Kumar; Kar, Tapan Kumar

2018-05-01

We propose and analyze a mathematical model for tuberculosis (TB) transmission to study the role of exogenous reinfection and endogenous reactivation. The model exhibits two equilibria: a disease free and an endemic equilibria. We observe that the TB model exhibits transcritical bifurcation when basic reproduction number R0 = 1. Our results demonstrate that the disease transmission rate β and exogenous reinfection rate α plays an important role to change the qualitative dynamics of TB. The disease transmission rate β give rises to the possibility of backward bifurcation for R0 < 1, and hence the existence of multiple endemic equilibria one of which is stable and another one is unstable. Our analysis suggests that R0 < 1 may not be sufficient to completely eliminate the disease. We also investigate that our TB transmission model undergoes Hopf-bifurcation with respect to the contact rate β and the exogenous reinfection rate α. We conducted some numerical simulations to support our analytical findings.

Carbohydrate and exercise performance: the role of multiple transportable carbohydrates.

PubMed

Jeukendrup, Asker E

2010-07-01

Carbohydrate feeding has been shown to be ergogenic, but recently substantial advances have been made in optimizing the guidelines for carbohydrate intake during prolonged exercise. It was found that limitations to carbohydrate oxidation were in the absorptive process most likely because of a saturation of carbohydrate transporters. By using a combination of carbohydrates that use different intestinal transporters for absorption it was shown that carbohydrate delivery and oxidation could be increased. Studies demonstrated increases in exogenous carbohydrate oxidation rates of up to 65% of glucose: fructose compared with glucose only. Exogenous carbohydrate oxidation rates reach values of 1.75 g/min whereas previously it was thought that 1 g/min was the absolute maximum. The increased carbohydrate oxidation with multiple transportable carbohydrates was accompanied by increased fluid delivery and improved oxidation efficiency, and thus the likelihood of gastrointestinal distress may be diminished. Studies also demonstrated reduced fatigue and improved exercise performance with multiple transportable carbohydrates compared with a single carbohydrate. Multiple transportable carbohydrates, ingested at high rates, can be beneficial during endurance sports in which the duration of exercise is 3 h or more.

Endogenous versus exogenous generic reference pricing for pharmaceuticals.

PubMed

Antoñanzas, F; Juárez-Castelló, C A; Rodríguez-Ibeas, R

2017-12-01

In this paper we carry out a vertical differentiation duopoly model applied to pharmaceutical markets to analyze how endogenous and exogenous generic reference pricing influence competition between generic and branded drugs producers. Unlike the literature, we characterize for the exogenous case the equilibrium prices for all feasible relevant reference prices. Competition is enhanced after the introduction of a reference pricing system. We also compare both reference pricing systems on welfare grounds, assuming two different objective functions for health authorities: (i) standard social welfare and (ii) gross consumer surplus net of total pharmaceutical expenditures. We show that regardless of the objective function, health authorities will never choose endogenous reference pricing. When health authorities are paternalistic, the exogenous reference price that maximizes standard social welfare is such that the price of the generic drug is the reference price while the price of the branded drug is higher than the reference price. When health authorities are not paternalistic, the optimal exogenous reference price is such that the price of the branded drug is the reference price while the price of the generic drug is lower than the reference price.

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

PubMed

Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-02-28

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

Arabidopsis phosphatidylinositol monophosphate 5-kinase 2 is involved in root gravitropism through regulation of polar auxin transport by affecting the cycling of PIN proteins.

PubMed

Mei, Yu; Jia, Wen-Jing; Chu, Yu-Jia; Xue, Hong-Wei

2012-03-01

Phosphatidylinositol monophosphate 5-kinase (PIP5K) catalyzes the synthesis of PI-4,5-bisphosphate (PtdIns(4,5)P(2)) by phosphorylation of PI-4-phosphate at the 5 position of the inositol ring, and is involved in regulating multiple developmental processes and stress responses. We here report on the functional characterization of Arabidopsis PIP5K2, which is expressed during lateral root initiation and elongation, and whose expression is enhanced by exogenous auxin. The knockout mutant pip5k2 shows reduced lateral root formation, which could be recovered with exogenous auxin, and interestingly, delayed root gravity response that could not be recovered with exogenous auxin. Crossing with the DR5-GUS marker line and measurement of free IAA content confirmed the reduced auxin accumulation in pip5k2. In addition, analysis using the membrane-selective dye FM4-64 revealed the decelerated vesicle trafficking caused by PtdIns(4,5)P(2) reduction, which hence results in suppressed cycling of PIN proteins (PIN2 and 3), and delayed redistribution of PIN2 and auxin under gravistimulation in pip5k2 roots. On the contrary, PtdIns(4,5)P(2) significantly enhanced the vesicle trafficking and cycling of PIN proteins. These results demonstrate that PIP5K2 is involved in regulating lateral root formation and root gravity response, and reveal a critical role of PIP5K2/PtdIns(4,5)P(2) in root development through regulation of PIN proteins, providing direct evidence of crosstalk between the phosphatidylinositol signaling pathway and auxin response, and new insights into the control of polar auxin transport.

Characterization of volatile sulfur compound production by Solobacterium moorei.

PubMed

Tanabe, Shin-ichi; Grenier, Daniel

2012-12-01

Solobacterium moorei is a Gram positive bacterium that has been specifically associated with halitosis. The aim of this study was to characterize volatile sulfur compound (VSC) production by S. moorei. S. moorei was either grown or incubated in the presence of various supplements prior to determining VSC production with a Halimeter sulfide monitor. The effect of exogenous proteases or glycosidase inhibitors on VSC production by S. moorei was examined. We first showed that S. moorei can convert cysteine into hydrogen sulfide. The capacity of S. moorei to produce VSCs from serum, saliva, and mucin was dependent on the presence of an exogenous source of proteases such as pancreatic trypsin or Porphyromonas gingivalis gingipains. VSC production from mucin was inhibited by the presence of a β-galactosidase inhibitor, thus suggesting that deglycosylation of mucin by S. moorei is critical for VSC production. Our study suggests that S. moorei can be a major source of malodorous compounds in halitosis by producing VSCs through a process involving the β-galactosidase activity of the bacterium and an exogenous source of proteases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Phylogenetic characterization of Clonorchis sinensis proteins homologous to the sigma-class glutathione transferase and their differential expression profiles.

PubMed

Bae, Young-An; Kim, Jeong-Geun; Kong, Yoon

2016-01-01

Glutathione transferase (GST) is one of the major antioxidant proteins with diverse supplemental activities including peroxidase, isomerase, and thiol transferase. GSTs are classified into multiple classes on the basis of their primary structures and substrate/inhibitor specificity. However, the evolutionary routes and physiological environments specific to each of the closely related bioactive enzymes remain elusive. The sigma-like GSTs exhibit amino acid conservation patterns similar to the prostaglandin D synthases (PGDSs). In this study, we analyzed the phylogenetic position of the GSTs of the biocarcinogenic liver fluke, Clonorchis sinensis. We also observed induction profile of the GSTs in association with the parasite's maturation and in response to exogenous oxidative stresses, with special attention to sigma-class GSTs and PGDSs. The C. sinensis genome encoded 12 GST protein species, which were separately assigned to cytosolic (two omega-, one zeta-, two mu-, and five sigma-class), mitochondrial (one kappa-class), and microsomal (one membrane-associated proteins in eicosanoid and glutathione metabolism-like protein) GST families. Multiple sigma GST (or PGDS) orthologs were also detected in Opisthorchis viverrini. Other trematode species possessed only a single sigma-like GST gene. A phylogenetic analysis demonstrated that one of the sigma GST lineages duplicated in the common ancestor of trematodes were specifically expanded in the opisthorchiids, but deleted in other trematodes. The induction profiles of these sigma GST genes along with the development and aging of C. sinensis, and against various exogenous chemical stimuli strongly suggest that the paralogous sigma GST genes might be undergone specialized evolution to cope with the diverse hostile biochemical environments within the mammalian hepatobiliary ductal system. Copyright © 2016 Elsevier B.V. All rights reserved.

Drought and exogenous abscisic acid alter hydrogen peroxide accumulation and differentially regulate the expression of two maize RD22-like genes.

PubMed

Phillips, Kyle; Ludidi, Ndiko

2017-08-18

Increased biosynthesis of abscisic acid (ABA) occurs in plants in response to water deficit, which is mediated by changes in the levels of reactive oxygen species such as H 2 O 2 . Water deficit and ABA induce expression of some RD22-like proteins. This study aimed to evaluate the effect of water deficit and exogenous ABA (50 µM ABA applied every 24 hours for a total of 72 hours) on H 2 O 2 content in Zea mays (maize) and to characterise genes encoding two putative maize RD22-like proteins (designated ZmRD22A and ZmRD22B). The expression profiles of the two putative maize RD22-like genes in response to water deficit and treatment with ABA were examined in leaves. In silico analyses showed that the maize RD22-like proteins share domain organisation with previously characterized RD22-like proteins. Both water deficit and exogenous ABA resulted in increased H 2 O 2 content in leaves but the increase was more pronounced in response to water deficit than to exogenous ABA. Lignin content was not affected by exogenous ABA, whereas it was decreased by water deficit. Expression of both RD22-like genes was up-regulated by drought but the ZmRD22A gene was not influenced by exogenous ABA, whereas ZmRD22B was highly responsive to exogenous ABA.

Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro

PubMed Central

Purohit, Nupur K.; Robu, Mihaela; Shah, Rashmi G.; Geacintov, Nicholas E.; Shah, Girish M.

2016-01-01

The existing methodologies for studying robust responses of poly (ADP-ribose) polymerase-1 (PARP-1) to DNA damage with strand breaks are often not suitable for examining its subtle responses to altered DNA without strand breaks, such as UV-damaged DNA. Here we describe two novel assays with which we characterized the interaction of PARP-1 with UV-damaged DNA in vivo and in vitro. Using an in situ fractionation technique to selectively remove free PARP-1 while retaining the DNA-bound PARP-1, we demonstrate a direct recruitment of the endogenous or exogenous PARP-1 to the UV-lesion site in vivo after local irradiation. In addition, using the model oligonucleotides with single UV lesion surrounded by multiple restriction enzyme sites, we demonstrate in vitro that DDB2 and PARP-1 can simultaneously bind to UV-damaged DNA and that PARP-1 casts a bilateral asymmetric footprint from −12 to +9 nucleotides on either side of the UV-lesion. These techniques will permit characterization of different roles of PARP-1 in the repair of UV-damaged DNA and also allow the study of normal housekeeping roles of PARP-1 with undamaged DNA. PMID:26753915

Stimulation of a Ca sup 2+ -dependent protein kinase by G sub M1 ganglioside in nerve growth factor-treated PC12 cells

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

Hilbush, B.S.; Levine, J.M.

1991-07-01

The authors have investigated the ability of exogenous gangliosides to modulate nerve growth factor (NGF) signal transduction in PC12 cells. The effects of exogenous ganglioside G{sub M1} on multiple protein kinase activities were assayed by analyzing site-specific serine phosphorylation of tyrosine hydroxylase (TyrOHase) by two-dimensional phosphopeptide mapping. In the presence of NGF, exogenous G{sub M1} increased {sup 32}P incorporation into TyrOHase phosphopeptide T2, a Ca{sup 2+}/calmodulin-dependent protein kinase substrate whose phosphorylation is not normally affected by NGF treatment. In the absence of NGF, G{sub M1} treatment had no significant effects on TyrOHase phosphorylation. The removal of extracellular Ca{sup 2+} ormore » blockade of dihydropyridine-sensitive Ca{sup 2+} channels prevented the G{sub M1}-induced increases in {sup 32}P incorporation into phosphopeptide T2. Exogenous G{sub M1} also potentiated K{sup +} depolarization-induced increases in the phosphorylation of TyrOHase. These results suggest that the stimulatory effects of exogenous G{sub M1} ganglioside on NGF actions may be due to its ability to potentiate a Ca{sup 2+}-dependent signaling pathway.« less

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma

PubMed Central

Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-01-01

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides “killing” PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors. PMID:28146424

Surfactant Therapy of ALI and ARDS

PubMed Central

Raghavendran, K; Willson, D; Notter, RH

2011-01-01

This article examines exogenous lung surfactant replacement therapy and its utility in mitigating clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Biophysical research has documented that lung surfactant dysfunction can be reversed or mitigated by increasing surfactant concentration, and multiple studies in animals with ALI/ARDS have shown that respiratory function and pulmonary mechanics in vivo can be improved by exogenous surfactant administration. Exogenous surfactant therapy is a routine intervention in neonatal intensive care, and is life-saving in preventing or treating the neonatal respiratory distress syndrome (NRDS) in premature infants. In applications relevant for lung injury-related respiratory failure and ALI/ARDS, surfactant therapy has been shown to be beneficial in term infants with pneumonia and meconium aspiration lung injury, and in children up to age 21 with direct pulmonary forms of ALI/ARDS. However, extension of exogenous surfactant therapy to adults with respiratory failure and clinical ALI/ARDS remains a challenge. Coverage here reviews clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS, particularly focusing on its potential advantages in patients with direct pulmonary forms of these syndromes. Also discussed is the rationale for mechanism-based therapies utilizing exogenous surfactant in combination with agents targeting other aspects of the multifaceted pathophysiology of inflammatory lung injury. Additional factors affecting the efficacy of exogenous surfactant therapy in ALI/ARDS are also described, including the difficulty of effectively delivering surfactants to injured lungs and the existence of activity differences between clinical surfactant drugs. PMID:21742216

Simultaneous quantification of endogenous and exogenous plasma glucose by isotope dilution LC-MS/MS with indirect MRM of the derivative tag.

PubMed

Yu, Lingling; Wen, Chao; Li, Xing; Fang, Shiqi; Yang, Lichuan; Wang, Tony; Hu, Kaifeng

2018-03-01

Quantification of endogenous and exogenous plasma glucose can help more comprehensively evaluate the glucose metabolic status. A ratio-based approach using isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was developed to simultaneously quantify endo-/exogenous plasma glucose. Using diluted D-[ 13 C 6 ] glucose as tracer of exogenous glucose, 12 C 6 / 13 C 6 glucoses were first derivatized and then data were acquired in MRM mode. The metabolism of exogenous glucose can be tracked and the concentration ratio of endo/exo-genous glucose can be measured by calculating the endo-/exo-genous glucose concentrations from peak area ratio of specific daughter ions. Joint application of selective derivatization and MRM analysis not only improves the sensitivity but also minimizes the interference from the background of plasma, which warrants the accuracy and reproducibility. Good agreement between the theoretical and calculated concentration ratios was obtained with a linear correlation coefficient (R) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which covers the healthy and diabetic physiological scenarios. Satisfactory reproducibility was obtained by evaluation of the intra- and inter-day precisions with relative standard deviations (RSDs) less than 5.16%, and relative recoveries of 85.96 to 95.92% were obtained at low, medium, and high concentration, respectively. The method was successfully applied to simultaneous determination of the endo-/exogenous glucose concentration in plasma of non-diabetic and type II diabetic cynomolgus monkeys. Graphical Abstract The scheme of the proposed ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the derivative tag for simultaneous quantification of endogenous and exogenous plasma glucose.

Psyche: State of Knowledge from Ground-Based Observations

NASA Astrophysics Data System (ADS)

Reddy, V.; Shepard, M. K.; Takir, D.; Sanchez, J. A.; Richardson, J.; Emery, J. P.; Taylor, P. A.

2017-07-01

We present results from a multi-year campaign to characterize asteroid (16) Psyche, the target of NASA Discovery mission. Our results suggest that Psyche is covered with exogenic carbonaceous impactor similar to Vesta.

Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers

PubMed Central

Li, Yuanpei; Xiao, Kai; Zhu, Wei; Deng, Wenbin; Lam, Kit S.

2013-01-01

Stimuli-responsive cross-linked micelles (SCMs) represent an ideal nanocarrier system for drug delivery against cancers. SCMs exhibit superior structural stability compared to their non-crosslinked counterpart. Therefore, these nanocarriers are able to minimize the premature drug release during blood circulation. The introduction of environmentally sensitive crosslinkers or assembly units makes SCMs responsive to single or multiple stimuli present in tumor local microenvironment or exogenously applied stimuli. In these instances, the payload drug is released almost exclusively in cancerous tissue or cancer cells upon accumulation via enhanced permeability and retention effect or receptor mediated endocytosis. In this review, we highlight recent advances in the development of SCMs for cancer therapy. We also introduce the latest biophysical techniques, such as electron paramagnetic resonance (EPR) spectroscopy and fluorescence resonance energy transfer (FRET), for the characterization of the interactions between SCMs and blood proteins. PMID:24060922

Amnion: a potent graft source for cell therapy in stroke.

PubMed

Yu, Seong Jin; Soncini, Maddalena; Kaneko, Yuji; Hess, David C; Parolini, Ornella; Borlongan, Cesar V

2009-01-01

Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

Engineered M13 bacteriophage nanocarriers for intracellular delivery of exogenous proteins to human prostate cancer cells.

PubMed

DePorter, Sandra M; McNaughton, Brian R

2014-09-17

The size, well-defined structure, and relatively high folding energies of most proteins allow them to recognize disease-relevant receptors that present a challenge to small molecule reagents. While multiple challenges must be overcome in order to fully exploit the use of protein reagents in basic research and medicine, perhaps the greatest challenge is their intracellular delivery to a particular diseased cell. Here, we describe the genetic and enzymatic manipulation of prostate cancer cell-penetrating M13 bacteriophage to generate nanocarriers for the intracellular delivery of functional exogenous proteins to a human prostate cancer cell line.

Comparative proteomic and physiological analyses reveal the protective effect of exogenous polyamines in the bermudagrass (Cynodon dactylon) response to salt and drought stresses.

PubMed

Shi, Haitao; Ye, Tiantian; Chan, Zhulong

2013-11-01

Polyamines conferred enhanced abiotic stress tolerance in multiple plant species. However, the effect of polyamines on abiotic stress and physiological change in bermudagrass, the most widely used warm-season turfgrasses, are unknown. In this study, pretreatment of exogenous polyamine conferred increased salt and drought tolerances in bermudagrass. Comparative proteomic analysis was performed to further investigate polyamines mediated responses, and 36 commonly regulated proteins by at least two types of polyamines in bermudagrass were successfully identified, including 12 proteins with increased level, 20 proteins with decreased level and other 4 specifically expressed proteins. Among them, proteins involved in electron transport and energy pathways were largely enriched, and nucleoside diphosphate kinase (NDPK) and three antioxidant enzymes were extensively regulated by polyamines. Dissection of reactive oxygen species (ROS) levels indicated that polyamine-derived H2O2 production might play dual roles under abiotic stress conditions. Moreover, accumulation of osmolytes was also observed after application of exogenous polyamines, which is consistent with proteomics results that several proteins involved in carbon fixation pathway were mediated commonly by polyamines pretreatment. Taken together, we proposed that polyamines could activate multiple pathways that enhance bermudagrass adaption to salt and drought stresses. These findings might be applicable for genetically engineering of grasses and crops to improve stress tolerance.

Exogenous application of hydrogen sulfide donor sodium hydrosulfide enhanced multiple abiotic stress tolerance in bermudagrass (Cynodon dactylon (L). Pers.).

PubMed

Shi, Haitao; Ye, Tiantian; Chan, Zhulong

2013-10-01

As a gaseous molecule, hydrogen sulfide (H2S) has been recently found to be involved in plant responses to multiple abiotic stress. In this study, salt (150 and 300 mM NaCl), osmotic (15% and 30% PEG6000) and cold (4 °C) stress treatments induced accumulation of endogenous H2S level, indicating that H2S might play a role in bermudagrass responses to salt, osmotic and cold stresses. Exogenous application of H2S donor (sodium hydrosulfide, NaHS) conferred improved salt, osmotic and freezing stress tolerances in bermudagrass, which were evidenced by decreased electrolyte leakage and increased survival rate under stress conditions. Additionally, NaHS treatment alleviated the reactive oxygen species (ROS) burst and cell damage induced by abiotic stress, via modulating metabolisms of several antioxidant enzymes [catalase (CAT), peroxidase (POD) and GR (glutathione reductase)] and non-enzymatic glutathione antioxidant pool and redox state. Moreover, exogenous NaHS treatment led to accumulation of osmolytes (proline, sucrose and soluble total sugars) in stressed bermudagrass plants. Taken together, all these data indicated the protective roles of H2S in bermudagrass responses to salt, osmotic and freezing stresses, via activation of the antioxidant response and osmolyte accumulation. These findings might be applicable to grass and crop engineering to improve abiotic stress tolerance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Effect of storage temperature on endogenous GHB levels in urine.

PubMed

LeBeau, M A; Miller, M L; Levine, B

2001-06-15

Because gamma-hydroxybutyrate (GHB) is an endogenous substance present in the body and is rapidly eliminated after ingestion, toxicologists investigating drug-facilitated sexual assault cases are often asked to differentiate between endogenous and exogenous levels of GHB in urine samples. This study was designed to determine the effects of storage temperature on endogenous GHB levels in urine. Specifically, it was designed to ascertain whether endogenous levels can be elevated to a range considered indicative of GHB ingestion. Urine specimens from two subjects that had not been administered exogenous GHB were collected during a 24h period and individually pooled. The pooled specimens were separated into standard sample cups and divided into three storage groups: room temperature ( approximately 25 degrees C), refrigerated (5 degrees C), and frozen (-10 degrees C). Additionally, some specimens were put through numerous freeze/thaw cycles to mimic situations that may occur if multiple laboratories analyze the same specimen. Periodic analysis of the samples revealed increases in the levels of endogenous GHB over a 6-month period. The greatest increase (up to 404%) was observed in the samples maintained at room temperature. The refrigerated specimens showed increases of 140-208%, while the frozen specimens showed smaller changes (88-116%). The specimens subjected to multiple freeze/thaw cycles mirrored specimens that had been thawed only once. None of the stored urine specimens demonstrated increases in GHB concentrations that would be consistent with exogenous GHB ingestion.

Causal relationship model between variables using linear regression to improve professional commitment of lecturer

NASA Astrophysics Data System (ADS)

Setyaningsih, S.

2017-01-01

The main element to build a leading university requires lecturer commitment in a professional manner. Commitment is measured through willpower, loyalty, pride, loyalty, and integrity as a professional lecturer. A total of 135 from 337 university lecturers were sampled to collect data. Data were analyzed using validity and reliability test and multiple linear regression. Many studies have found a link on the commitment of lecturers, but the basic cause of the causal relationship is generally neglected. These results indicate that the professional commitment of lecturers affected by variables empowerment, academic culture, and trust. The relationship model between variables is composed of three substructures. The first substructure consists of endogenous variables professional commitment and exogenous three variables, namely the academic culture, empowerment and trust, as well as residue variable ɛ y . The second substructure consists of one endogenous variable that is trust and two exogenous variables, namely empowerment and academic culture and the residue variable ɛ 3. The third substructure consists of one endogenous variable, namely the academic culture and exogenous variables, namely empowerment as well as residue variable ɛ 2. Multiple linear regression was used in the path model for each substructure. The results showed that the hypothesis has been proved and these findings provide empirical evidence that increasing the variables will have an impact on increasing the professional commitment of the lecturers.

Epidemiological investigations into multiple sclerosis in southern Hesse. II. The distribution of cases in relation to exogenous features.

PubMed

Lauer, K; Firnhaber, W

1984-10-01

In order to discover possible exogenous variables associated with a higher multiple sclerosis risk, the distribution of cases with definite and probable multiple sclerosis ascertained in the course of a micro-epidemiologic study in Southern Hesse was evaluated and compared with some environmental factors. The prevalence in 1980, the prevalence of cases with disease-onset within the region according to locality of onset and the rate of native Southern Hesse patients according to childhood residence all showed a similar geographical distribution, with the highest values in the south-eastern, mountainous part of the region. This district has a lower annual mean temperature, more annual snow-days and a higher annual precipitation compared to the remaining area. A statistical comparison revealed no association with industrial or agricultural activities, with a particular type of land use, with cattle, pig- or horse-breeding, or with sanitary or housing standards. On the other hand, a slight association with the soil type could be demonstrated, with higher rates on loam and clay subsoils when compared to predominantly sandy regions. Whether this finding has any significance or not remains to be clarified.

Glucose enhances tilapia against Edwardsiella tarda infection through metabolome reprogramming.

PubMed

Zeng, Zao-hai; Du, Chao-Chao; Liu, Shi-Rao; Li, Hui; Peng, Xuan-Xian; Peng, Bo

2017-02-01

We have recently reported that the survival of tilapia, Oreochromis niloticus, during Edwardsiella tarda infection is tightly associated with their metabolome, where the survived O. niloticus has distinct metabolomic profile to dying O. niloticus. Glucose is the key metabolite to distinguish the survival- and dying-metabolome. More importantly, exogenous administration of glucose to the fish greatly enhances their survival for the infection, indicating the functional roles of glucose in metabolome repurposing, known as reprogramming metabolomics. However, the underlying information for the reprogramming is not yet available. Here, GC/MS based metabolomics is used to understand the mechanisms by which how exogenous glucose elevates O. niloticus, anti-infectious ability to E. tarda. Results showed that exogenous glucose promotes stearic acid and palmitic acid biosynthesis but attenuates TCA cycle to potentiate O. niloticus against bacterial infection, which is confirmed by the fact that exogenous stearic acid increases immune protection in O. niloticus against E. tarda infection in a manner of Mx protein. These results indicate that exogenous glucose reprograms O. niloticus anti-infective metabolome that characterizes elevation of stearic acid and palmitic acid and attenuation of the TCA cycle. Therefore, our results proposed a novel mechanism that glucose promotes unsaturated fatty acid biosynthesis to cope with infection, thereby highlighting a potential way of enhancing fish immunity in aquaculture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Message survival and decision dynamics in a class of reactive complex systems subject to external fields

NASA Astrophysics Data System (ADS)

Rodriguez Lucatero, C.; Schaum, A.; Alarcon Ramos, L.; Bernal-Jaquez, R.

2014-07-01

In this study, the dynamics of decisions in complex networks subject to external fields are studied within a Markov process framework using nonlinear dynamical systems theory. A mathematical discrete-time model is derived using a set of basic assumptions regarding the convincement mechanisms associated with two competing opinions. The model is analyzed with respect to the multiplicity of critical points and the stability of extinction states. Sufficient conditions for extinction are derived in terms of the convincement probabilities and the maximum eigenvalues of the associated connectivity matrices. The influences of exogenous (e.g., mass media-based) effects on decision behavior are analyzed qualitatively. The current analysis predicts: (i) the presence of fixed-point multiplicity (with a maximum number of four different fixed points), multi-stability, and sensitivity with respect to the process parameters; and (ii) the bounded but significant impact of exogenous perturbations on the decision behavior. These predictions were verified using a set of numerical simulations based on a scale-free network topology.

A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron.

PubMed

Horn, Nikki; Carvalho, Ana L; Overweg, Karin; Wegmann, Udo; Carding, Simon R; Stentz, Régis

2016-01-01

There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI)-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterized Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter-region of an α-1,2-mannosidase gene (BT_3784), a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products.

Modeling the spread of tuberculosis in semiclosed communities.

PubMed

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play.

Modeling the Spread of Tuberculosis in Semiclosed Communities

PubMed Central

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play. PMID:23762194

Exogenous γ-aminobutyric acid (GABA) affects pollen tube growth via modulating putative Ca2+-permeable membrane channels and is coupled to negative regulation on glutamate decarboxylase

PubMed Central

Yu, Guang-Hui; Zou, Jie; Feng, Jing; Peng, Xiong-Bo; Wu, Ju-You; Wu, Ying-Liang; Palanivelu, Ravishankar; Sun, Meng-Xiang

2014-01-01

γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes. PMID:24799560

IL-22 promotes Fas expression in oligodendrocytes and inhibits FOXP3 expression in T cells by activating the NF-κB pathway in multiple sclerosis.

PubMed

Zhen, Jin; Yuan, Jun; Fu, Yongwang; Zhu, Runxiu; Wang, Meiling; Chang, Hong; Zhao, Yan; Wang, Dong; Lu, Zuneng

2017-02-01

Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4 + CCR4 + CCR6 + CCR10 + T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells. Depending on exogenous IL-22, Fas increased the phosphorylation of mitogen- and stress-activated protein kinase 1 and activated the nuclear factor-κB pathway in oligodendrocytes, leading to an increase in Fas and oligodendrocyte apoptosis. IL-22 decreased FOXP3 expression by activating NF-κB, and it further inhibited PTEN and Ikaros expression. Tregs reversed the functions of IL-22. Taken together, these findings help to elucidate the mechanisms of IL-22 in MS development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum.

PubMed

Tang, Yuanman; Liu, Qiuping; Liu, Ying; Zhang, Linli; Ding, Wei

2017-01-01

Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA)-responsive genes NtPR1a/c , NtPR2 and NtCHN50 , JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26 . Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum . Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

Elbow joint angle and elbow movement velocity estimation using NARX-multiple layer perceptron neural network model with surface EMG time domain parameters.

PubMed

Raj, Retheep; Sivanandan, K S

2017-01-01

Estimation of elbow dynamics has been the object of numerous investigations. In this work a solution is proposed for estimating elbow movement velocity and elbow joint angle from Surface Electromyography (SEMG) signals. Here the Surface Electromyography signals are acquired from the biceps brachii muscle of human hand. Two time-domain parameters, Integrated EMG (IEMG) and Zero Crossing (ZC), are extracted from the Surface Electromyography signal. The relationship between the time domain parameters, IEMG and ZC with elbow angular displacement and elbow angular velocity during extension and flexion of the elbow are studied. A multiple input-multiple output model is derived for identifying the kinematics of elbow. A Nonlinear Auto Regressive with eXogenous inputs (NARX) structure based multiple layer perceptron neural network (MLPNN) model is proposed for the estimation of elbow joint angle and elbow angular velocity. The proposed NARX MLPNN model is trained using Levenberg-marquardt based algorithm. The proposed model is estimating the elbow joint angle and elbow movement angular velocity with appreciable accuracy. The model is validated using regression coefficient value (R). The average regression coefficient value (R) obtained for elbow angular displacement prediction is 0.9641 and for the elbow anglular velocity prediction is 0.9347. The Nonlinear Auto Regressive with eXogenous inputs (NARX) structure based multiple layer perceptron neural networks (MLPNN) model can be used for the estimation of angular displacement and movement angular velocity of the elbow with good accuracy.

Transcriptomic Profiling Analysis of Arabidopsis thaliana Treated with Exogenous Myo-Inositol

PubMed Central

Ye, Wenxing; Ren, Weibo; Kong, Lingqi; Zhang, Wanjun; Wang, Tao

2016-01-01

Myo-insositol (MI) is a crucial substance in the growth and developmental processes in plants. It is commonly added to the culture medium to promote adventitious shoot development. In our previous work, MI was found in influencing Agrobacterium-mediated transformation. In this report, a high-throughput RNA sequencing technique (RNA-Seq) was used to investigate differently expressed genes in one-month-old Arabidopsis seedling grown on MI free or MI supplemented culture medium. The results showed that 21,288 and 21,299 genes were detected with and without MI treatment, respectively. The detected genes included 184 new genes that were not annotated in the Arabidopsis thaliana reference genome. Additionally, 183 differentially expressed genes were identified (DEGs, FDR ≤0.05, log2 FC≥1), including 93 up-regulated genes and 90 down-regulated genes. The DEGs were involved in multiple pathways, such as cell wall biosynthesis, biotic and abiotic stress response, chromosome modification, and substrate transportation. Some significantly differently expressed genes provided us with valuable information for exploring the functions of exogenous MI. RNA-Seq results showed that exogenous MI could alter gene expression and signaling transduction in plant cells. These results provided a systematic understanding of the functions of exogenous MI in detail and provided a foundation for future studies. PMID:27603208

Structural and functional diversity of CLAVATA3/ESR (CLE)-like genes from the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Chen, Shiyan; Wang, Jianying; Yu, Hang; Chronis, Demosthenis; Mitchum, Melissa G; Wang, Xiaohong

2009-09-01

Plant CLAVATA3/ESR-related (CLE) peptides have diverse roles in plant growth and development. Here, we report the isolation and functional characterization of five new CLE genes from the potato cyst nematode Globodera rostochiensis. Unlike typical plant CLE peptides that contain a single CLE motif, four of the five Gr-CLE genes encode CLE proteins with multiple CLE motifs. These Gr-CLE genes were found to be specifically expressed within the dorsal esophageal gland cell of nematode parasitic stages, suggesting a role for their encoded proteins in plant parasitism. Overexpression phenotypes of Gr-CLE genes in Arabidopsis mimicked those of plant CLE genes, and Gr-CLE proteins could rescue the Arabidopsis clv3-2 mutant phenotype when expressed within meristems. A short root phenotype was observed when synthetic GrCLE peptides were exogenously applied to roots of Arabidopsis or potato similar to the overexpression of Gr-CLE genes in Arabidopsis and potato hairy roots. These results reveal that G. rostochiensis CLE proteins with either single or multiple CLE motifs function similarly to plant CLE proteins and that CLE signaling components are conserved in both Arabidopsis and potato roots. Furthermore, our results provide evidence to suggest that the evolution of multiple CLE motifs may be an important mechanism for generating functional diversity in nematode CLE proteins to facilitate parasitism.

Exogenous Ochronosis

PubMed Central

Bhattar, Prachi A; Zawar, Vijay P; Godse, Kiran V; Patil, Sharmila P; Nadkarni, Nitin J; Gautam, Manjyot M

2015-01-01

Exogenous ochronosis (EO) is a cutaneous disorder characterized by blue-black pigmentation resulting as a complication of long-term application of skin-lightening creams containing hydroquinone but may also occur due to topical contact with phenol or resorcinol in dark-skinned individuals. It can also occur following the use of systemic antimalarials such as quinine. EO is clinically and histologically similar to its endogenous counterpart viz., alkaptonuria, which, however, exhibits systemic effects and is an inherited disorder. Dermoscopy and in vivo skin reflectance confocal microscopy are noninvasive in vivo diagnostic tools. It is very difficult to treat EO, a cosmetically disfiguring and troubling disorder with disappointing treatment options. PMID:26677264

Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

PubMed

Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

2011-01-01

Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Characterization of the endolysin from the Enterococcus faecalis bacteriophage VD13

USDA-ARS?s Scientific Manuscript database

Bacteriophage infecting bacteria produce endolysins (peptidoglycan hydrolases) to lyse the host cell from within and release nascent bacteriophage particles. Recombinant endolysins can also lyse Gram-positive bacteria when added exogenously. As a potential alternative to antibiotics, we cloned and...

Flanking sequence determination and specific PCR identification of transgenic wheat B102-1-2.

PubMed

Cao, Jijuan; Xu, Junyi; Zhao, Tongtong; Cao, Dongmei; Huang, Xin; Zhang, Piqiao; Luan, Fengxia

2014-01-01

The exogenous fragment sequence and flanking sequence between the exogenous fragment and recombinant chromosome of transgenic wheat B102-1-2 were successfully acquired using genome walking technology. The newly acquired exogenous fragment encoded the full-length sequence of transformed genes with transformed plasmid and corresponding functional genes including ubi, vector pBANF-bar, vector pUbiGUSPlus, vector HSP, reporter vector pUbiGUSPlus, promoter ubiquitin, and coli DH1. A specific polymerase chain reaction (PCR) identification method for transgenic wheat B102-1-2 was established on the basis of designed primers according to flanking sequence. This established specific PCR strategy was validated by using transgenic wheat, transgenic corn, transgenic soybean, transgenic rice, and non-transgenic wheat. A specifically amplified target band was observed only in transgenic wheat B102-1-2. Therefore, this method is characterized by high specificity, high reproducibility, rapid identification, and excellent accuracy for the identification of transgenic wheat B102-1-2.

Clinical phenotype and infertility treatment in a male with hypogonadotropic hypogonadism due to mutations Ala129Asp/Arg262Gln of the gonadotropin-releasing hormone receptor.

PubMed

Layman, Lawrence C; Cohen, David P; Xie, Jun; Smith, Gary D

2002-12-01

To characterize the genotype and phenotype of a man with idiopathic hypogonadism with infertility. Molecular analysis and clinical description. Medical school laboratory and reproductive endocrine clinic.A 40-year-old male with idiopathic hypogonadotropic hypogonadism. Denaturing gradient gel electrophoresis analysis and DNA sequencing of the gonadotropin-releasing hormone receptor (GNRHR) gene were performed. The patient was treated with hCG and FSH. GNRHR mutation detection, genotype/phenotype correlation, and testicular response to exogenous gonadotropin therapy. The proband demonstrated compound heterozygosity for Ala129Asp/Arg262Gln GNRHR mutations. He had a complete form of idiopathic hypogonadotropic hypogonadism, with descended testes and severe oligospermia but little response to exogenous gonadotropins. The phenotype of this patient differs from the one other family described with the same mutations. Exogenous gonadotropin therapy may not be as beneficial for increasing sperm concentration in older men with idiopathic hypogonadotropic hypogonadism.

Environmental Sources of Bacteria Differentially Influence Host-Associated Microbial Dynamics.

PubMed

Cardona, Cesar; Lax, Simon; Larsen, Peter; Stephens, Brent; Hampton-Marcell, Jarrad; Edwardson, Christian F; Henry, Chris; Van Bonn, Bill; Gilbert, Jack A

2018-01-01

Host-associated microbial dynamics are influenced by dietary and immune factors, but how exogenous microbial exposure shapes host-microbe dynamics remains poorly characterized. To investigate this phenomenon, we characterized the skin, rectum, and respiratory tract-associated microbiota in four aquarium-housed dolphins daily over a period of 6 weeks, including administration of a probiotic during weeks 4 to 6. The environmental bacterial sources were also characterized, including the animals' human handlers, the aquarium air and water, and the dolphins' food supply. Continuous microbial exposure occurred between all sites, yet each environment maintained a characteristic microbiota, suggesting that the majority of exposure events do not result in colonization. Small changes in water physicochemistry had a significant but weak correlation with change in dolphin-associated bacterial richness but had no influence on phylogenetic diversity. Food and air microbiota were the richest and had the largest conditional influence on other microbiota in the absence of probiotics, but during probiotic administration, food alone had the largest influence on the stability of the dolphin microbiota. Our results suggest that respiratory tract and gastrointestinal epithelium interactions with air- and food-associated microbes had the biggest influence on host-microbiota dynamics, while other interactions, such as skin transmission, played only a minor role. Finally, direct oral stimulation with a foreign exogenous microbial source can have a profound effect on microbial stability. IMPORTANCE These results provide valuable insights into the ecological influence of exogenous microbial exposure, as well as laying the foundation for improving aquarium management practices. By comparing data for dolphins from aquaria that use natural versus artificial seawater, we demonstrate the potential influence of aquarium water disinfection procedures on dolphin microbial dynamics.

Exogenous and endogenous hormones and breast cancer

PubMed Central

ChenMD, Wendy Y.

2008-01-01

Exposure to higher levels of both exogenous and endogenous hormone is associated with breast cancer risk. Because of the association between breast cancer and HRT, only the minimal duration of HRT use is recommended for symptom control, and it is not recommended for chronic disease management. Current research issues include the role of progestins, other types of HRT, duration of unopposed estrogen use, and characteristics of cancers that develop on HRT. Circulating sex steroid levels are associated with breast cancer risk, but multiple issues need to be addressed before they are used routinely in clinical practice. Current research issues include measurement of levels for routine clinical practice, integration with standard breast cancer risk models and genetic polymorphism data, and applicability to estrogen-receptor-negative cancers. PMID:18971119

Exogenous Attention Influences Visual Short-Term Memory in Infants

ERIC Educational Resources Information Center

Ross-Sheehy, Shannon; Oakes, Lisa M.; Luck, Steven J.

2011-01-01

Two experiments examined the hypothesis that developing visual attentional mechanisms influence infants' Visual Short-Term Memory (VSTM) in the context of multiple items. Five- and 10-month-old infants (N = 76) received a change detection task in which arrays of three differently colored squares appeared and disappeared. On each trial one square…

Atrazine-induced elevation or attenuation of the LH surge in the ovariectomized, estrogen-primed female rat: role of adrenal progesterone

EPA Science Inventory

Multiple daily exposures to the herbicide atrazine have been reported to suppress the surge of luteinizing hormone (LH) in both cycling female rats and those that are ovariectomized (OVX) and exogenously primed with steroids. Additional studies have also found elevations in both ...

The effect of plant growth regulators on apple graft union flexural strength and flexibility

USDA-ARS?s Scientific Manuscript database

The apple rootstock ‘Geneva® 41’ (‘G.41’) forms weak graft unions with multiple scions. Exogenous plant growth regulators (PGR) can influence vascular differentiation and wood formation, and thus may improve graft union strength. A series of commercial and experimental PGR formulations were applied ...

The interactive effects of press/pulse intensity and duration on regime shifts at multiple scales

USDA-ARS?s Scientific Manuscript database

Regime shifts are difficult-to-reverse transitions that occur when an ecosystem reorganizes around a new set of self-reinforcing feedbacks. Regime shifts are predicted to occur when the intensity of some exogenous driver variable, such as temperature, annual harvest rate, or nutrient addition rate, ...

In-vivo characterization of endogenous porphyrin fluorescence from DMBA-treated Swiss Albino mice skin carcinogenesis for measuring tissue transformation

NASA Astrophysics Data System (ADS)

Ganesan, Singaravelu; Ebenezar, Jeyasingh; Hemamalini, Srinivasan; Aruna, Prakasa R.

2002-05-01

Steady state fluorescence spectroscopic characterization of endogenous porphyrin emission from DMBA treated skin carcinogenesis in Swiss albino mice was carried out. The emission of endogenous porphyrin from normal and abnormal skin tissues was studied both in the presence and absence of exogenous ALA to compare the resultant porphyrin emission characterictics. The mice skin is excited at 405nm and emission spectra are scanned from 430 to 700nm. The average fluorescence emission spectra of mice skin at normal and various tissues transformation conditions were found to be different. Two peaks around 460nm and 636nm were observed and they may be attributed to NADH, Elastin and collagen combination and endogenous porphyrin emission. The intensity at 636nm increases as the stage of the cancer increases. Although exogenous ALA enhances the PPIX level in tumor, the synthesis of PPIX was also found in normal surrounding skin, in fact, with higher concentration than that of tumor tissues.

A Novel Tightly Regulated Gene Expression System for the Human Intestinal Symbiont Bacteroides thetaiotaomicron

PubMed Central

Horn, Nikki; Carvalho, Ana L.; Overweg, Karin; Wegmann, Udo; Carding, Simon R.; Stentz, Régis

2016-01-01

There is considerable interest in studying the function of Bacteroides species resident in the human gastrointestinal (GI)-tract and the contribution they make to host health. Reverse genetics and protein expression techniques, such as those developed for well-characterized Escherichia coli cannot be applied to Bacteroides species as they and other members of the Bacteriodetes phylum have unique promoter structures. The availability of useful Bacteroides-specific genetic tools is therefore limited. Here we describe the development of an effective mannan-controlled gene expression system for Bacteroides thetaiotaomicron containing the mannan-inducible promoter–region of an α-1,2-mannosidase gene (BT_3784), a ribosomal binding site designed to modulate expression, a multiple cloning site to facilitate the cloning of genes of interest, and a transcriptional terminator. Using the Lactobacillus pepI as a reporter gene, mannan induction resulted in an increase of reporter activity in a time- and concentration-dependent manner with a wide range of activity. The endogenous BtcepA cephalosporinase gene was used to demonstrate the suitability of this novel expression system, enabling the isolation of a His-tagged version of BtCepA. We have also shown with experiments performed in mice that the system can be induced in vivo in the presence of an exogenous source of mannan. By enabling the controlled expression of endogenous and exogenous genes in B. thetaiotaomicron this novel inducer-dependent expression system will aid in defining the physiological role of individual genes and the functional analyses of their products. PMID:27468280

A Summary of the Biological Basis of Frailty.

PubMed

Fielding, Roger A

2015-01-01

Frailty has been defined as a geriatric syndrome that is characterized by a reduction in the physiological reserve required for an individual to respond to endogenous and exogenous stressors. Using a discrete definition of frailty that includes sedentariness, involuntary weight loss, fatigue, poor muscle strength, and slow gait speed, 'frailty' has been associated with increased disability, postsurgical complications, and increased mortality. Despite the strong associations between frailty and subsequent poor outcomes, limited attention to this common geriatric condition has been paid in clinical settings. A more fundamental basic understanding of the biological factors that contribute to the frailty phenotype has begun to emerge. Multiple underlying biological factors such as dysregulation of inflammatory processes, genomic instability, oxidative stress, mitochondrial dysfunction, and cellular senescence appear to contribute to the clinical presentation of frailty. This chapter summarizes the papers presented on the biological basis of frailty from the 83rd Nestlé Nutrition Institute Workshop on 'Frailty, Pathophysiology, Phenotype and Patient Care' held in Barcelona, Spain, in March 2014. © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel.

GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis.

PubMed

Qin, Jing; Sikkema, Arend H; van der Bij, Kristine; de Jonge, Jenny C; Klappe, Karin; Nies, Vera; Jonker, Johan W; Kok, Jan Willem; Hoekstra, Dick; Baron, Wia

2017-10-11

Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides (i.e., cell surface lipids with a potential to modulate signaling pathways) could counteract fibronectin-mediated inhibition of OPC maturation. Exclusive exposure of rat oligodendrocytes to GD1a, but not other gangliosides, overcomes aggregated fibronectin-induced inhibition of myelin membrane formation, in vitro , and OPC differentiation in fibronectin aggregate containing cuprizone-induced demyelinated lesions in male mice. GD1a exerts its effect on OPCs by inducing their proliferation and, at a late stage, by modulating OPC maturation. Kinase activity profiling revealed that GD1a activated a protein kinase A (PKA)-dependent signaling pathway and increased phosphorylation of the transcription factor cAMP response element-binding protein. Consistently, the effect of GD1a in restoring myelin membrane formation in the presence of fibronectin aggregates was abolished by the PKA inhibitor H89, whereas the effect of GD1a was mimicked by the PKA activator dibutyryl-cAMP. Together, GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation by activating a PKA-dependent signaling pathway. Given the persistent presence of fibronectin aggregates in MS lesions, ganglioside GD1a might act as a potential novel therapeutic tool to selectively modulate the detrimental signaling environment that precludes remyelination. SIGNIFICANCE STATEMENT As an environmental factor, aggregates of the extracellular matrix protein fibronectin perturb the maturation of oligodendrocyte progenitor cells (OPCs), thereby impeding remyelination, in the demyelinating disease multiple sclerosis (MS). Here we demonstrate that exogenous addition of ganglioside GD1a overcomes the inhibiting effect of aggregated fibronectin on OPC maturation, both in vitro and in vivo , by activating a PKA-dependent signaling pathway. We propose that targeted delivery of GD1a to MS lesions may act as a potential novel molecular tool to boost maturation of resident OPCs to overcome remyelination failure and halt disease progression. Copyright © 2017 the authors 0270-6474/17/379925-14$15.00/0.

Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

PubMed

Sasaki, Yo; Araki, Toshiyuki; Milbrandt, Jeffrey

2006-08-16

Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop

EPA Science Inventory

Lysosomes have a central role in cellular catabolism, trafficking, and processing of foreign particles. Accumulation of endogenous and exogenous materials in lysosomes represents a common finding in nonclinical toxicity studies. Histologically, these accumulations often lack dist...

Sequence genomic organization and expression of two channel catfish Ictalurus punctatus Ghrelin receptors

USDA-ARS?s Scientific Manuscript database

Two ghrelin receptor (GHS-R) genes were isolated from channel catfish tissue and a bacterial artificial chromosome (BAC) library. The two receptors were characterized by determining tissue distribution, ontogeny of receptor mRNA expression, and effects of exogenous homologous ghrelin administration ...

Social Interactions under Incomplete Information: Games, Equilibria, and Expectations

NASA Astrophysics Data System (ADS)

Yang, Chao

My dissertation research investigates interactions of agents' behaviors through social networks when some information is not shared publicly, focusing on solutions to a series of challenging problems in empirical research, including heterogeneous expectations and multiple equilibria. The first chapter, "Social Interactions under Incomplete Information with Heterogeneous Expectations", extends the current literature in social interactions by devising econometric models and estimation tools with private information in not only the idiosyncratic shocks but also some exogenous covariates. For example, when analyzing peer effects in class performances, it was previously assumed that all control variables, including individual IQ and SAT scores, are known to the whole class, which is unrealistic. This chapter allows such exogenous variables to be private information and models agents' behaviors as outcomes of a Bayesian Nash Equilibrium in an incomplete information game. The distribution of equilibrium outcomes can be described by the equilibrium conditional expectations, which is unique when the parameters are within a reasonable range according to the contraction mapping theorem in function spaces. The equilibrium conditional expectations are heterogeneous in both exogenous characteristics and the private information, which makes estimation in this model more demanding than in previous ones. This problem is solved in a computationally efficient way by combining the quadrature method and the nested fixed point maximum likelihood estimation. In Monte Carlo experiments, if some exogenous characteristics are private information and the model is estimated under the mis-specified hypothesis that they are known to the public, estimates will be biased. Applying this model to municipal public spending in North Carolina, significant negative correlations between contiguous municipalities are found, showing free-riding effects. The Second chapter "A Tobit Model with Social Interactions under Incomplete Information", is an application of the first chapter to censored outcomes, corresponding to the situation when agents" behaviors are subjected to some binding restrictions. In an interesting empirical analysis for property tax rates set by North Carolina municipal governments, it is found that there is a significant positive correlation among near-by municipalities. Additionally, some private information about its own residents is used by a municipal government to predict others' tax rates, which enriches current empirical work about tax competition. The third chapter, "Social Interactions under Incomplete Information with Multiple Equilibria", extends the first chapter by investigating effective estimation methods when the condition for a unique equilibrium may not be satisfied. With multiple equilibria, the previous model is incomplete due to the unobservable equilibrium selection. Neither conventional likelihoods nor moment conditions can be used to estimate parameters without further specifications. Although there are some solutions to this issue in the current literature, they are based on strong assumptions such as agents with the same observable characteristics play the same strategy. This paper relaxes those assumptions and extends the all-solution method used to estimate discrete choice games to a setting with both discrete and continuous choices, bounded and unbounded outcomes, and a general form of incomplete information, where the existence of a pure strategy equilibrium has been an open question for a long time. By the use of differential topology and functional analysis, it is found that when all exogenous characteristics are public information, there are a finite number of equilibria. With privately known exogenous characteristics, the equilbria can be represented by a compact set in a Banach space and be approximated by a finite set. As a result, a finite-state probability mass function can be used to specify a probability measure for equilibrium selection, which completes the model. From Monte Carlo experiments about two types of binary choice models, it is found that assuming equilibrium uniqueness can bring in estimation biases when the true value of interaction intensity is large and there are multiple equilibria in the data generating process.

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

PubMed

Pryce, Gareth; Ahmed, Zubair; Hankey, Deborah J R; Jackson, Samuel J; Croxford, J Ludovic; Pocock, Jennifer M; Ledent, Catherine; Petzold, Axel; Thompson, Alan J; Giovannoni, Gavin; Cuzner, M Louise; Baker, David

2003-10-01

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

A Paradigm for Virus–Host Coevolution: Sequential Counter-Adaptations between Endogenous and Exogenous Retroviruses

PubMed Central

Arnaud, Frederick; Caporale, Marco; Varela, Mariana; Biek, Roman; Chessa, Bernardo; Alberti, Alberto; Golder, Matthew; Mura, Manuela; Zhang, Ya-ping; Yu, Li; Pereira, Filipe; DeMartini, James C; Leymaster, Kreg; Spencer, Thomas E; Palmarini, Massimo

2007-01-01

Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that some ERVs are used by the host as restriction factors to block the infection of pathogenic retroviruses. Indeed, some ERVs efficiently interfere with the replication of related exogenous retroviruses. However, data suggesting that these mechanisms have influenced the coevolution of endogenous and/or exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model system to study retrovirus-host coevolution because of the coexistence in this animal species of two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, Jaagsiekte sheep retrovirus and Enzootic nasal tumor virus, with highly related and biologically active endogenous retroviruses (enJSRVs). Here, we isolated and characterized the evolutionary history and molecular virology of 27 enJSRV proviruses. enJSRVs have been integrating in the host genome for the last 5–7 million y. Two enJSRV proviruses (enJS56A1 and enJSRV-20), which entered the host genome within the last 3 million y (before and during speciation within the genus Ovis), acquired in two temporally distinct events a defective Gag polyprotein resulting in a transdominant phenotype able to block late replication steps of related exogenous retroviruses. Both transdominant proviruses became fixed in the host genome before or around sheep domestication (∼ 9,000 y ago). Interestingly, a provirus escaping the transdominant enJSRVs has emerged very recently, most likely within the last 200 y. Thus, we determined sequentially distinct events during evolution that are indicative of an evolutionary antagonism between endogenous and exogenous retroviruses. This study strongly suggests that endogenization and selection of ERVs acting as restriction factors is a mechanism used by the host to fight retroviral infections. PMID:17997604

MLV integration site selection is driven by strong enhancers and active promoters

PubMed Central

LaFave, Matthew C.; Varshney, Gaurav K.; Gildea, Derek E.; Wolfsberg, Tyra G.; Baxevanis, Andreas D.; Burgess, Shawn M.

2014-01-01

Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors. PMID:24464997

Opioid growth factor and low-dose naltrexone impair central nervous system infiltration by CD4 + T lymphocytes in established experimental autoimmune encephalomyelitis, a model of multiple sclerosis.

PubMed

Hammer, Leslie A; Waldner, Hanspeter; Zagon, Ian S; McLaughlin, Patricia J

2016-01-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating myelin-reactive T lymphocytes and demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is the animal model widely utilized to study MS. EAE is mediated by CD4(+) T cells and can be induced in EAE-susceptible mice through immunization with a myelin antigen, such as proteolipid protein 139-151 (PLP139-151) in SJL mice. In this PLP-induced EAE model, autoreactive CD4(+) T cells migrate from peripheral tissues into the CNS where they are reactivated resulting in CNS damage. Th1 and Th17 cells produce the pro-inflammatory cytokines IFNγ and IL-17, respectively, that have been shown to have pathogenic roles in EAE and MS. Anti-inflammatory Th2, IL-4 secreting cells, have been indicated to inhibit EAE exacerbation. However, given the inflammatory environment of EAE, Th2 effector cells are outnumbered by Th1/Th17 cells. Regulatory CD4(+) T cells suppress immune reactions and have been demonstrated to be dysfunctional in MS patients. Opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin, is a negative growth factor that interacts with the OGF receptor. The OGF-OGFr axis can be activated through exogenous administration of OGF or a low dosage of naltrexone (LDN), an opioid antagonist. We have previously demonstrated that modulation of the OGF-OGFr axis results in alleviation from relapse-remitting EAE, and that CNS-infiltrating CD3(+) T cells are diminished with exogenous OGF or intermittent blockade with LDN administration. In this paper, we aimed to determine whether OGF or LDN alter the Th effector responses of CD4(+) T lymphocytes within the CNS in established EAE. We report in these studies that the numbers of CD4(+) T lymphocytes in the CNS of EAE mice are decreased following treatment with OGF for five days but not LDN. However, modulation of the OGF-OGFr axis did not result in changes to CD4(+) Th effector cell responses in the CNS of EAE mice. © 2016 by the Society for Experimental Biology and Medicine.

Effects of copyrolysis of sludge with calcium carbonate and calcium hydrogen phosphate on chemical stability of carbon and release of toxic elements in the resultant biochars.

PubMed

Xu, Xuebin; Hu, Xin; Ding, Zhuhong; Chen, Yijun

2017-12-01

The potential release of toxic elements and the stability of carbon in sludge-based biochars are important on their application in soil remediation and wastewater treatment. In this study, municipal sludge was co-pyrolyzed with calcium carbonate (CaCO 3 ) and calcium dihydrogen phosphate [Ca(H 2 PO 4 ) 2 ] under 300 and 600 °C, respectively. The basic physicochemical properties of the resultant biochars were characterized and laboratory chemical oxidation and leaching experiments of toxic elements were conducted to evaluate the chemical stability of carbon in biochars and the potential release of toxic elements from biochars. Results show that the exogenous minerals changed the physico-chemical properties of the resultant biochars greatly. Biochars with exogenous minerals, especially Ca(H 2 PO 4 ) 2 , decreased the release of Zn, Cr, Ni, Cu, Pb, and As and the release ratios were less than 1%. Tessier's sequential extraction analysis revealed that labile toxic elements were transferred to residual fraction in the biochars with high pyrolysis temperature (600 °C) and exogenous minerals. Low risks for biochar-bound Pb, Zn, Cd, As, Cr, and Cu were confirmed according to risk assessment code (RAC) while the potential ecological risk index (PERI) revealed that the exogenous Ca(H 2 PO 4 ) 2 significantly decreased the risks from considerable to moderate level. Moreover, the exogenous minerals significantly increased the chemical stability of carbon in 600 °C-pyrolyzed biochars by 10-20%. These results indicated that the copyrolysis of sludge with phosphate and carbonate, especially phosphate, were effective methods to prepare the sludge-based biochars with immobilized toxic elements and enhanced chemical stability of carbon. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cooperation evolution in random multiplicative environments

NASA Astrophysics Data System (ADS)

Yaari, G.; Solomon, S.

2010-02-01

Most real life systems have a random component: the multitude of endogenous and exogenous factors influencing them result in stochastic fluctuations of the parameters determining their dynamics. These empirical systems are in many cases subject to noise of multiplicative nature. The special properties of multiplicative noise as opposed to additive noise have been noticed for a long while. Even though apparently and formally the difference between free additive vs. multiplicative random walks consists in just a move from normal to log-normal distributions, in practice the implications are much more far reaching. While in an additive context the emergence and survival of cooperation requires special conditions (especially some level of reward, punishment, reciprocity), we find that in the multiplicative random context the emergence of cooperation is much more natural and effective. We study the various implications of this observation and its applications in various contexts.

Mixed Infections and their Control

DTIC Science & Technology

1983-04-29

endocarditis , bactereF.,;a, and closed-space infections , such as brain or lung abscesses that cavnot be surgically drained. Combination therapy should not be...Systemic infection is a common complication of multiple injury despite the availability of potent and specific antibiotics. 2 Infections following...trauma are due to opportunistic pathogens that . originate from endogenous nr exogenous sources. These pathogens, often present as mixed infections

The Impacts of Family Size on Investment in Child Quality

ERIC Educational Resources Information Center

Caceres-Delpiano, Julio

2006-01-01

Using multiple births as an exogenous shift in family size, I investigate the impact of the number of children on child investment and child well-being. Using data from the 1980 US Census Five-Percent Public Use Micro Sample, 2SLS results demonstrate that parents facing a change in family size reallocate resources in a way consistent with Becker's…

The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in both Healthy and Disease-affected Skin

PubMed Central

Del Rosso, James Q.; Levin, Jacqueline

2011-01-01

It has been recognized for approximately 50 years that the stratum corneum exhibits biological properties that contribute directly to maintaining and sustaining healthy skin. Continued basic science and clinical research coupled with keen clinical observation has led to more recent recognition and general acceptance that the stratum corneum completes many vital “barrier” tasks, including but not limited to regulating epidermal water content and the magnitude of water loss; mitigating exogenous oxidants that can damage components of skin via an innate antioxidant system; preventing or limiting cutaneous infection via multiple antimicrobial peptides; responding via innate immune mechanisms to “cutaneous invaders” of many origins, including microbes, true allergens, and other antigens; and protecting its neighboring cutaneous cells and structures that lie beneath from damaging effects of ultraviolet radiation. Additionally, specific abnormalities of the stratum corneum are associated with the clinical expression of certain disease states. This article provides a thorough “primer” for the clinician, reviewing the multiple normal homeostatic functions of the stratum corneum and the cutaneous challenges that arise when individual functions of this thin yet very active epidermal layer are compromised by exogenous and/or endogenous factors. PMID:21938268

Attachment defect in mouse fibroblasts (L cells) persistently infected with Chlamydia psittaci.

PubMed Central

Moulder, J W; Levy, N J; Zeichner, S L; Lee, C K

1981-01-01

Almost all the cells in populations of mouse fibroblasts (L cells) persistently infected with the 6BC strain of Chlamydia psittaci were immune to superinfection with high multiplicities of C. psittaci, whether or not the L cells contained visible chlamydial inclusions. As ascertained by experiments with 14C-labeled C. psittaci, immunity to superinfection resulted from the failure of added chlamydiae to attach to persistently infected host cells. However, when exogenous C. psittaci was introduced into persistently infected L cells by centrifuging the inoculum onto host cell monolayers or by pretreating the monolayers with diethylaminoethyl-dextran, these chlamydiae produced expected numbers of infectious progeny. Persistently infected L cells were associated in an unknown way with a C. psittaci population that entered the host cells only with the aid of centrifugation or pretreatment with diethylaminoethyl-dextran. Inclusion-free, persistently infected L cells appeared to present at least two separate hindrances to chlamydial activity: blockage of the attachment of exogenous elementary bodies to persistently infected host cells and prevention of the initiation of chlamydial multiplication by means of a normal developmental cycle in the absence of added C. psittaci. Images PMID:7298188

Adenosine transiently modulates stimulated dopamine release in the caudate putamen via A1 receptors

PubMed Central

Ross, Ashley E.; Venton, B. Jill

2014-01-01

Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5 s before stimulation. Longer time intervals and bath application of 5 µM adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2s before dopamine stimulation also decreased stimulated dopamine release by 41 ± 7 %, similar to the 54 ± 6 % decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10 minutes. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A2A receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A1 receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain. PMID:25219576

COMMON ISSUES IN HUMAN AND ECOSYSTEM EXPOSURE ASSESSMENT: THE SIGNIFICANCE OF PARTITIONING, KINETICS, AND UPTAKE AT BIOLOGICAL EXCHANGE SURFACES

EPA Science Inventory

Exogenous chemicals enter organisms through critical surfaces in the lung, gills, gut, and skin. Transfer across these boundaries is the first step in characterizing the ratio of tissue dose to external exposure. Surface processes and fugacity are important elements of both human...

Alternatives to vitamin B 1 uptake revealed with discovery of riboswitches in multiple marine eukaryotic lineages

DOE PAGES

McRose, Darcy; Guo, Jian; Monier, Adam; ...

2014-08-29

Here, vitamin B 1 (thiamine pyrophosphate, TPP) is essential to all life but scarce in ocean surface waters. In many bacteria and a few eukaryotic groups thiamine biosynthesis genes are controlled by metabolite-sensing mRNA-based gene regulators known as riboswitches. Using available genome sequences and transcriptomes generated from ecologically important marine phytoplankton, we identified 31 new eukaryotic riboswitches. These were found in alveolate, cryptophyte, haptophyte and rhizarian phytoplankton as well as taxa from two lineages previously known to have riboswitches (green algae and stramenopiles). The predicted secondary structures bear hallmarks of TPP-sensing riboswitches. Surprisingly, most of the identified riboswitches are affiliatedmore » with genes of unknown function, rather than characterized thiamine biosynthesis genes. Using qPCR and growth experiments involving two prasinophyte algae, we show that expression of these genes increases significantly under vitamin B 1-deplete conditions relative to controls. Pathway analyses show that several algae harboring the uncharacterized genes lack one or more enzymes in the known TPP biosynthesis pathway. We demonstrate that one such alga, the major primary producer Emiliania huxleyi, grows on 4-amino-5-hydroxymethyl-2-methylpyrimidine (a thiamine precursor moiety) alone, although long thought dependent on exogenous sources of thiamine. Thus, overall, we have identified riboswitches in major eukaryotic lineages not known to undergo this form of gene regulation. In these phytoplankton groups, riboswitches are often affiliated with widespread thiamine-responsive genes with as yet uncertain roles in TPP pathways. Further, taxa with ‘incomplete’ TPP biosynthesis pathways do not necessarily require exogenous vitamin B 1, making vitamin control of phytoplankton blooms more complex than the current paradigm suggests.« less

Alternatives to vitamin B 1 uptake revealed with discovery of riboswitches in multiple marine eukaryotic lineages

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

McRose, Darcy; Guo, Jian; Monier, Adam

Here, vitamin B 1 (thiamine pyrophosphate, TPP) is essential to all life but scarce in ocean surface waters. In many bacteria and a few eukaryotic groups thiamine biosynthesis genes are controlled by metabolite-sensing mRNA-based gene regulators known as riboswitches. Using available genome sequences and transcriptomes generated from ecologically important marine phytoplankton, we identified 31 new eukaryotic riboswitches. These were found in alveolate, cryptophyte, haptophyte and rhizarian phytoplankton as well as taxa from two lineages previously known to have riboswitches (green algae and stramenopiles). The predicted secondary structures bear hallmarks of TPP-sensing riboswitches. Surprisingly, most of the identified riboswitches are affiliatedmore » with genes of unknown function, rather than characterized thiamine biosynthesis genes. Using qPCR and growth experiments involving two prasinophyte algae, we show that expression of these genes increases significantly under vitamin B 1-deplete conditions relative to controls. Pathway analyses show that several algae harboring the uncharacterized genes lack one or more enzymes in the known TPP biosynthesis pathway. We demonstrate that one such alga, the major primary producer Emiliania huxleyi, grows on 4-amino-5-hydroxymethyl-2-methylpyrimidine (a thiamine precursor moiety) alone, although long thought dependent on exogenous sources of thiamine. Thus, overall, we have identified riboswitches in major eukaryotic lineages not known to undergo this form of gene regulation. In these phytoplankton groups, riboswitches are often affiliated with widespread thiamine-responsive genes with as yet uncertain roles in TPP pathways. Further, taxa with ‘incomplete’ TPP biosynthesis pathways do not necessarily require exogenous vitamin B 1, making vitamin control of phytoplankton blooms more complex than the current paradigm suggests.« less

Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens

PubMed Central

Niu, Jun; Wang, Jia; Hu, Huiwen; Chen, Yinlei; An, Jiyong; Cai, Jian; Sun, Runze; Sheng, Zhongting; Liu, Xieping; Lin, Shanzhi

2016-01-01

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5′ deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process. PMID:26853706

International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

PubMed Central

2015-01-01

Estrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including the reproductive, cardiovascular, endocrine, nervous, and immune systems. As such, alterations in estrogen function play important roles in many diseases and pathophysiological conditions (including cancer), exemplified by the lower prevalence of many diseases in premenopausal women. Estrogens mediate their effects through multiple cellular receptors, including the nuclear receptor family (ERα and ERβ) and the G protein–coupled receptor (GPCR) family (GPR30/G protein–coupled estrogen receptor [GPER]). Although both receptor families can initiate rapid cell signaling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signaling. Estrogen-activated pathways are not only the target of multiple therapeutic agents (e.g., tamoxifen, fulvestrant, raloxifene, and aromatase inhibitors) but are also affected by a plethora of phyto- and xeno-estrogens (e.g., genistein, coumestrol, bisphenol A, dichlorodiphenyltrichloroethane). Because of the existence of multiple estrogen receptors with overlapping ligand specificities, expression patterns, and signaling pathways, the roles of the individual receptors with respect to the diverse array of endogenous and exogenous ligands have been challenging to ascertain. The identification of GPER-selective ligands however has led to a much greater understanding of the roles of this receptor in normal physiology and disease as well as its interactions with the classic estrogen receptors ERα and ERβ and their signaling pathways. In this review, we describe the history and characterization of GPER over the past 15 years focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor. PMID:26023144

International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators.

PubMed

Prossnitz, Eric R; Arterburn, Jeffrey B

2015-07-01

Estrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including the reproductive, cardiovascular, endocrine, nervous, and immune systems. As such, alterations in estrogen function play important roles in many diseases and pathophysiological conditions (including cancer), exemplified by the lower prevalence of many diseases in premenopausal women. Estrogens mediate their effects through multiple cellular receptors, including the nuclear receptor family (ERα and ERβ) and the G protein-coupled receptor (GPCR) family (GPR30/G protein-coupled estrogen receptor [GPER]). Although both receptor families can initiate rapid cell signaling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signaling. Estrogen-activated pathways are not only the target of multiple therapeutic agents (e.g., tamoxifen, fulvestrant, raloxifene, and aromatase inhibitors) but are also affected by a plethora of phyto- and xeno-estrogens (e.g., genistein, coumestrol, bisphenol A, dichlorodiphenyltrichloroethane). Because of the existence of multiple estrogen receptors with overlapping ligand specificities, expression patterns, and signaling pathways, the roles of the individual receptors with respect to the diverse array of endogenous and exogenous ligands have been challenging to ascertain. The identification of GPER-selective ligands however has led to a much greater understanding of the roles of this receptor in normal physiology and disease as well as its interactions with the classic estrogen receptors ERα and ERβ and their signaling pathways. In this review, we describe the history and characterization of GPER over the past 15 years focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Assembly of transcriptionally inactive chromatin in vitro.

PubMed

Shanahan, M M; Kmiec, E B

1989-07-01

We have successfully uncoupled the previously interlocked activities of chromatin assembly and in vitro transcription promoted by the Xenopus oocyte S-150 cell-free extract. Our isolated fraction catalyzes extensive chromatin assembly measured both by changes in DNA topology and Micrococcal nuclease digestions. The assembly of chromatin is slowed by the exogenous addition of ATP. In the absence of exogenously added ATP, the fraction forms a chromatin template that is transcriptionally inert. Addition of small amounts of the HeLa cell extract (S-100) converts these templates into transcriptionally active ones without disrupting the chromatin structure. Our protocol defines a method for the isolation of a fraction from the Xenopus cell free extract that catalyzes the assembly of transcriptionally inactive chromatin. We characterize this reaction and establish conditions for the transcriptional activation of these inactive minichromosomes.

Structural principles within the human-virus protein-protein interaction network

PubMed Central

Franzosa, Eric A.; Xia, Yu

2011-01-01

General properties of the antagonistic biomolecular interactions between viruses and their hosts (exogenous interactions) remain poorly understood, and may differ significantly from known principles governing the cooperative interactions within the host (endogenous interactions). Systems biology approaches have been applied to study the combined interaction networks of virus and human proteins, but such efforts have so far revealed only low-resolution patterns of host-virus interaction. Here, we layer curated and predicted 3D structural models of human-virus and human-human protein complexes on top of traditional interaction networks to reconstruct the human-virus structural interaction network. This approach reveals atomic resolution, mechanistic patterns of host-virus interaction, and facilitates systematic comparison with the host’s endogenous interactions. We find that exogenous interfaces tend to overlap with and mimic endogenous interfaces, thereby competing with endogenous binding partners. The endogenous interfaces mimicked by viral proteins tend to participate in multiple endogenous interactions which are transient and regulatory in nature. While interface overlap in the endogenous network results largely from gene duplication followed by divergent evolution, viral proteins frequently achieve interface mimicry without any sequence or structural similarity to an endogenous binding partner. Finally, while endogenous interfaces tend to evolve more slowly than the rest of the protein surface, exogenous interfaces—including many sites of endogenous-exogenous overlap—tend to evolve faster, consistent with an evolutionary “arms race” between host and pathogen. These significant biophysical, functional, and evolutionary differences between host-pathogen and within-host protein-protein interactions highlight the distinct consequences of antagonism versus cooperation in biological networks. PMID:21680884

Insulin immuno-neutralization decreases food intake in chickens without altering hypothalamic mRNA levels for genes involved in regulation of food intake and metabolism

USDA-ARS?s Scientific Manuscript database

Chickens are characterized by rather unique glucose homeostasis, with relatively high blood glucose levels, reduced glucose sensitivity of pancreatic cells, and large resistance to exogenous insulin. In mammals, insulin regulates blood glucose level but also plays a key role in appetite regulation ...

Modeling the hypothalamus-pituitary-adrenal axis: A review and extension.

PubMed

Hosseinichimeh, Niyousha; Rahmandad, Hazhir; Wittenborn, Andrea K

2015-10-01

Multiple models of the hypothalamus-pituitary-adrenal (HPA) axis have been developed to characterize the oscillations seen in the hormone concentrations and to examine HPA axis dysfunction. We reviewed the existing models, then replicated and compared five of them by finding their correspondence to a dataset consisting of ACTH and cortisol concentrations of 17 healthy individuals. We found that existing models use different feedback mechanisms, vary in the level of details and complexities, and offer inconsistent conclusions. None of the models fit the validation dataset well. Therefore, we re-calibrated the best performing model using partial calibration and extended the model by adding individual fixed effects and an exogenous circadian function. Our estimated parameters reduced the mean absolute percent error significantly and offer a validated reference model that can be used in diverse applications. Our analysis suggests that the circadian and ultradian cycles are not created endogenously by the HPA axis feedbacks, which is consistent with the recent literature on the circadian clock and HPA axis. Copyright © 2015 Elsevier Inc. All rights reserved.

The regulation of the SARK promoter activity by hormones and environmental signals.

PubMed

Delatorre, Carla A; Cohen, Yuval; Liu, Li; Peleg, Zvi; Blumwald, Eduardo

2012-09-01

The Senescence Associated Receptor Protein Kinase (P(SARK)) promoter, fused to isopentenyltransferase (IPT) gene has been shown to promote drought tolerance in crops. We dissected P(SARK) in order to understand the various elements associated with its activation and suppression. The activity of P(SARK) was higher in mature and early senescing leaves, and abiotic stress induced its activity in mature leaves. Bioinformatics analysis suggests the interactions of multiple cis-acting elements in the control of P(SARK) activity. In vitro gel shift assays and yeast one hybrid system revealed interactions of P(SARK) with transcription factors related to abscisic acid and cytokinin response. Deletion analysis of P(SARK), fused to GUS-reporter gene was used to identify specific regions regulating transcription under senescence or during drought stress. Effects of exogenous hormonal treatments were characterized in entire plants and in leaf disk assays, and regions responsive to various hormones were defined. Our results indicate a complex interaction of plant hormones and additional factors modulating P(SARK) activity under stress resulting in a transient induction of expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The Novel Wheat Transcription Factor TaNAC47 Enhances Multiple Abiotic Stress Tolerances in Transgenic Plants

PubMed Central

Zhang, Lina; Zhang, Lichao; Xia, Chuan; Zhao, Guangyao; Jia, Jizeng; Kong, Xiuying

2016-01-01

NAC transcription factors play diverse roles in plant development and responses to abiotic stresses. However, the biological roles of NAC family members in wheat are not well understood. Here, we reported the isolation and functional characterization of a novel wheat TaNAC47 gene. TaNAC47 encoded protein, localizing in the nucleus, is able to bind to the ABRE cis-element and transactivate transcription in yeast, suggesting that it likely functions as a transcriptional activator. We also showed that TaNAC47 is differentially expressed in different tissues, and its expression was induced by the stress treatments of salt, cold, polyethylene glycol and exogenous abscisic acid. Furthermore, overexpression of TaNAC47 in Arabidopsis resulted in ABA hypersensitivity and enhancing tolerance of transgenic plants to drought, salt, and freezing stresses. Strikingly, overexpression of TaNAC47 was found to activate the expression of downstream genes and change several physiological indices that may enable transgenic plants to overcome unfavorable environments. Taken together, these results uncovered an important role of wheat TaNAC47 gene in response to ABA and abiotic stresses. PMID:26834757

The Novel Wheat Transcription Factor TaNAC47 Enhances Multiple Abiotic Stress Tolerances in Transgenic Plants.

PubMed

Zhang, Lina; Zhang, Lichao; Xia, Chuan; Zhao, Guangyao; Jia, Jizeng; Kong, Xiuying

2015-01-01

NAC transcription factors play diverse roles in plant development and responses to abiotic stresses. However, the biological roles of NAC family members in wheat are not well understood. Here, we reported the isolation and functional characterization of a novel wheat TaNAC47 gene. TaNAC47 encoded protein, localizing in the nucleus, is able to bind to the ABRE cis-element and transactivate transcription in yeast, suggesting that it likely functions as a transcriptional activator. We also showed that TaNAC47 is differentially expressed in different tissues, and its expression was induced by the stress treatments of salt, cold, polyethylene glycol and exogenous abscisic acid. Furthermore, overexpression of TaNAC47 in Arabidopsis resulted in ABA hypersensitivity and enhancing tolerance of transgenic plants to drought, salt, and freezing stresses. Strikingly, overexpression of TaNAC47 was found to activate the expression of downstream genes and change several physiological indices that may enable transgenic plants to overcome unfavorable environments. Taken together, these results uncovered an important role of wheat TaNAC47 gene in response to ABA and abiotic stresses.

Self-Organization on Social Media: Endo-Exo Bursts and Baseline Fluctuations

PubMed Central

Oka, Mizuki; Hashimoto, Yasuhiro; Ikegami, Takashi

2014-01-01

A salient dynamic property of social media is bursting behavior. In this paper, we study bursting behavior in terms of the temporal relation between a preceding baseline fluctuation and the successive burst response using a frequency time series of 3,000 keywords on Twitter. We found that there is a fluctuation threshold up to which the burst size increases as the fluctuation increases and that above the threshold, there appears a variety of burst sizes. We call this threshold the critical threshold. Investigating this threshold in relation to endogenous bursts and exogenous bursts based on peak ratio and burst size reveals that the bursts below this threshold are endogenously caused and above this threshold, exogenous bursts emerge. Analysis of the 3,000 keywords shows that all the nouns have both endogenous and exogenous origins of bursts and that each keyword has a critical threshold in the baseline fluctuation value to distinguish between the two. Having a threshold for an input value for activating the system implies that Twitter is an excitable medium. These findings are useful for characterizing how excitable a keyword is on Twitter and could be used, for example, to predict the response to particular information on social media. PMID:25329610

TiO2 nanoparticles as exogenous contrast agent for 1 µm swept source optical coherence tomography: an in vitro study

NASA Astrophysics Data System (ADS)

Kumar, Atul; Mondal, Indranil; Roy, Poulomi; Poddar, Raju

2018-03-01

Optical coherence tomography (OCT) is a rapidly evolving, robust technology that has profoundly changed the practice of medical imaging. Swept source OCT (SSOCT) combines the standard time domain and the spatially encoded frequency domain OCT. We have employed a high-speed SSOCT system that utilizes a swept source laser with an A-scan rate of 100 kHz and a central wavelength of 1060 nm for the imaging of the tissue. SSOCT at 1060 nm allows for high penetration in the tissue. TiO2 nanoparticles (NPs) are mostly used for various experimental purposes as an exogenous imaging contrast agent. The in vitro imaging of chicken breast tissue is performed with and without the application of TiO2 NPs for exogenous contrast. Characterization of the chemically synthesized TiO2 NPs was done with dynamic light scattering and a scanning electron microscope method. The effect of TiO2 is studied at different exposure times. A significant improvement in the contrast to noise ratio has been observed through the in vitro imaging of a TiO2 treated tissue.

A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line.

PubMed

Collins, Adam; Huett, Alan

2018-05-15

We present a high-content screen (HCS) for the simultaneous analysis of multiple phenotypes in HeLa cells expressing an autophagy reporter (mcherry-LC3) and one of 224 GFP-fused proteins from the Crohn's Disease (CD)-associated bacterium, Adherent Invasive E. coli (AIEC) strain LF82. Using automated confocal microscopy and image analysis (CellProfiler), we localised GFP fusions within cells, and monitored their effects upon autophagy (an important innate cellular defence mechanism), cellular and nuclear morphology, and the actin cytoskeleton. This data will provide an atlas for the localisation of 224 AIEC proteins within human cells, as well as a dataset to analyse their effects upon many aspects of host cell morphology. We also describe an open-source, automated, image-analysis workflow to identify bacterial effectors and their roles via the perturbations induced in reporter cell lines when candidate effectors are exogenously expressed.

A reversible component of mitochondrial respiratory dysfunction in apoptosis can be rescued by exogenous cytochrome c

PubMed Central

Mootha, Vamsi K.; Wei, Michael C.; Buttle, Karolyn F.; Scorrano, Luca; Panoutsakopoulou, Vily; Mannella, Carmen A.; Korsmeyer, Stanley J.

2001-01-01

Multiple apoptotic pathways release cytochrome c from the mitochondrial intermembrane space, resulting in the activation of downstream caspases. In vivo activation of Fas (CD95) resulted in increased permeability of the mitochondrial outer membrane and depletion of cytochrome c stores. Serial measurements of oxygen consumption, NADH redox state and membrane potential revealed a loss of respiratory state transitions. This tBID-induced respiratory failure did not require any caspase activity. At early time points, re-addition of exogenous cytochrome c markedly restored respiratory functions. Over time, however, mitochondria showed increasing irreversible respiratory dysfunction as well as diminished calcium buffering. Electron microscopy and tomographic reconstruction revealed asymmetric mitochondria with blebs of herniated matrix, distended inner membrane and partial loss of cristae structure. Thus, apoptogenic redistribution of cytochrome c is responsible for a distinct program of mitochondrial respiratory dysfunction, in addition to the activation of downstream caspases. PMID:11179211

A common-path optical coherence tomography based electrode for structural imaging of nerves and recording of action potentials

NASA Astrophysics Data System (ADS)

Islam, M. Shahidul; Haque, Md. Rezuanul; Oh, Christian M.; Wang, Yan; Park, B. Hyle

2013-03-01

Current technologies for monitoring neural activity either use different variety of electrodes (electrical recording) or require contrast agents introduced exogenously or through genetic modification (optical imaging). Here we demonstrate an optical method for non-contact and contrast agent free detection of nerve activity using phase-resolved optical coherence tomography (pr-OCT). A common-path variation of the pr-OCT is recently implemented and the developed system demonstrated the capability to detect rapid transient structural changes that accompany neural spike propagation. No averaging over multiple trials was required, indicating its capability of single-shot detection of individual impulses from functionally stimulated Limulus optic nerve. The strength of this OCT-based optical electrode is that it is a contactless method and does not require any exogenous contrast agent. With further improvements in accuracy and sensitivity, this optical electrode will play a complementary role to the existing recording technologies in future.

Exogenous S100A8 protein inhibits PDGF-induced migration of airway smooth muscle cells in a RAGE-dependent manner.

PubMed

Xu, Yu-Dong; Wei, Ying; Wang, Yu; Yin, Lei-Miao; Park, Gyoung-Hee; Liu, Yan-Yan; Yang, Yong-Qing

2016-03-25

S100A8 is an important member of the S100 protein family, which is involved in intracellular and extracellular regulatory activities. We previously reported that the S100A8 protein was differentially expressed in the asthmatic respiratory tracts. To understand the potential role of S100A8 in asthma, we investigated the effect of recombinant S100A8 protein on the platelet-derived growth factor (PDGF)-induced migration of airway smooth muscle cells (ASMCs) and the underlying molecular mechanism by using multiple methods, such as impedance-based xCELLigence migration assay, transwell migration assays and wound-healing assays. We found that exogenous S100A8 protein significantly inhibited PDGF-induced ASMC migration. Furthermore, the migration inhibition effect of S100A8 was blocked by neutralizing antibody against the receptor for advanced glycation end-products (RAGE), a potential receptor for the S100A8 protein. These findings provide direct evidence that exogenous S100A8 protein inhibits the PDGF-induced migration of ASMCs through the membrane receptor RAGE. Our study highlights a novel role of S100A8 as a potential means of counteracting airway remodeling in chronic airway diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Native weeds and exotic plants: Relationships to disturbance in mixed-grass prairie

USGS Publications Warehouse

Larson, D.L.

2003-01-01

Disturbance frequently is implicated in the spread of invasive exotic plants. Disturbances may be broadly categorized as endogenous (e.g., digging by fossorial animals) or exogenous (e.g., construction and maintenance of roads and trails), just as weedy species may be native or exotic in origin. The objective of this study was to characterize and compare exotic and native weedy plant occurrence in and near three classes of disturbance -digging by prairie dogs (an endogenous disturbance to which native plants have had the opportunity to adapt), paved or gravel roads (an exogenous disturbance without natural precedent), and constructed trails (an exogenous disturbance with a natural precedent in trails created by movement of large mammals) - in three geographically separate national park units. I used plant survey data from the North and South Units of Theodore Roosevelt National Park and Wind Cave National Park in the northern mixed-grass prairie of western North and South Dakota, USA, to characterize the distribution of weedy native and exotic plants with respect to the three disturbance classes as well as areas adjacent to them. There were differences both in the susceptibility of the disturbance classes to invasion and in the distributions of native weeds and exotic species among the disturbance classes. Both exotic and native weedy species richness were greatest in prairie dog towns and community composition there differed most from undisturbed areas. Exotic species were more likely to thrive near roadways, where native weedy species were infrequently encountered. Exotic species were more likely to have spread beyond the disturbed areas into native prairie than were weedy native species. The response of individual exotic plant species to the three types of disturbance was less consistent than that of native weedy species across the three park units.

Characterization of the exogenous insert and development of event-specific PCR detection methods for genetically modified Huanong No. 1 papaya.

PubMed

Guo, Jinchao; Yang, Litao; Liu, Xin; Guan, Xiaoyan; Jiang, Lingxi; Zhang, Dabing

2009-08-26

Genetically modified (GM) papaya (Carica papaya L.), Huanong No. 1, was approved for commercialization in Guangdong province, China in 2006, and the development of the Huanong No. 1 papaya detection method is necessary for implementing genetically modified organism (GMO) labeling regulations. In this study, we reported the characterization of the exogenous integration of GM Huanong No. 1 papaya by means of conventional polymerase chain reaction (PCR) and thermal asymmetric interlaced (TAIL)-PCR strategies. The results suggested that one intact copy of the initial construction was integrated in the papaya genome and which probably resulted in one deletion (38 bp in size) of the host genomic DNA. Also, one unintended insertion of a 92 bp truncated NptII fragment was observed at the 5' end of the exogenous insert. Furthermore, we revealed its 5' and 3' flanking sequences between the insert DNA and the papaya genomic DNA, and developed the event-specific qualitative and quantitative PCR assays for GM Huanong No. 1 papaya based on the 5' integration flanking sequence. The relative limit of detection (LOD) of the qualitative PCR assay was about 0.01% in 100 ng of total papaya genomic DNA, corresponding to about 25 copies of papaya haploid genome. In the quantitative PCR, the limits of detection and quantification (LOD and LOQ) were as low as 12.5 and 25 copies of papaya haploid genome, respectively. In practical sample quantification, the quantified biases between the test and true values of three samples ranged from 0.44% to 4.41%. Collectively, we proposed that all of these results are useful for the identification and quantification of Huanong No. 1 papaya and its derivates.

Characterization of root agravitropism induced by genetic, chemical, and developmental constraints

NASA Technical Reports Server (NTRS)

Moore, R.; Fondren, W. M.; Marcum, H.

1987-01-01

The patterns and rates of organelle redistribution in columella (i.e., putative statocyte) cells of agravitropic agt mutants of Zea mays are not significantly different from those of columella cells in graviresponsive roots. Graviresponsive roots of Z. mays are characterized by a strongly polar movement of 45Ca2+ across the root tip from the upper to the lower side. Horizontally-oriented roots of agt mutants exhibit only a minimal polar transport of 45Ca2+. Exogenously-induced asymmetries of Ca result in curvature of agt roots toward the Ca source. A similar curvature can be induced by a Ca asymmetry in normally nongraviresponsive (i.e., lateral) roots of Phaseolus vulgaris. Similarly, root curvature can be induced by placing the roots perpendicular to an electric field. This electrotropism increased with 1) currents between 8-35 mA, and 2) time between 1-9 hr when the current is constant. Electrotropism is reduced significantly by treating roots with triiodobenzoic acid (TIBA), an inhibitor of auxin transport. These results suggest that 1) if graviperception occurs via the sedimentation of amyloplasts in columella cells, then nongraviresponsive roots apparently sense gravity as do graviresponsive roots, 2) exogenously-induced asymmetries of a gravitropic effector (i.e., Ca) can induce curvature of normally nongraviresponsive roots, 3) the gravity-induced downward movement of exogenously-applied 45Ca2+ across tips of graviresponsive roots does not occur in nongraviresponsive roots, 4) placing roots in an electrical field (i.e., one favoring the movement of ions such as Ca2+) induces root curvature, and 5) electrically-induced curvature is apparently dependent on auxin transport. These results are discussed relative to a model to account for the lack of graviresponsiveness by these roots.

Radiation-Induced Processing of Hydrocarbons in Environments Relevant to Pluto

DTIC Science & Technology

2001-05-07

energetic’ (characterized by high levels of electrical and geothermal activity) liquid water environment, are capable of generating significant prebiotic ...synthesis of biogenic molecules (Chyba & Sagan 1992). In this light, a potential cometary source of prebiotic organics (the precursors of biological...precursors for prebiotic molecules. This exogenous source of prebiotic organics on early Earth could provide an alternative method of accounting for

[The theory of the demographic transition as a reference for demo-economic models].

PubMed

Genne, M

1981-01-01

The aim of the theory of demographic transition (TTD) is to better understand the behavior and interrelationship of economic and demographic variables. There are 2 types of demo-economic models: 1) the malthusian models, which consider demographic variables as pure exogenous variables, and 2) the neoclassical models, which consider demographic variables as strictly endogenous. If TTD can explore the behavior of exogenous and endogenous demographic variables, it cannot demonstrate neither the relation nor the order of causality among the various demographic and economic variables, but it is simply the theoretical framework of a complex social and economic phenomenon which started in Europe in the 19th Century, and which today can be extended to developing countries. There are 4 stages in the TTD; the 1st stage is characterized by high levels of fecundity and mortality; the 2nd stage is characterized by high fecundity levels and declining mortality levels; the 3rd stage is characterized by declining fecundity levels and low mortality levels; the 4th stage is characterized by low fertility and mortality levels. The impact of economic variables over mortality and birth rates is evident for mortality rates, which decline earlier and at a greater speed than birth rates. According to reliable mathematical predictions, around the year 1987 mortality rates in developing countries will have reached the low level of European countries, and growth rate will be only 1.5%. If the validity of demo-economic models has not yet been established, TTD has clearly shown that social and economic development is the factor which influences demographic expansion.

Endogenous and exogenous control of ecosystem function: N cycling in headwater streams.

PubMed

Valett, H M; Thomas, S A; Mulholland, P J; Webster, J R; Dahm, C N; Fellows, C S; Crenshaw, C L; Peterson, C G

2008-12-01

Allochthonous inputs act as resource subsidies to many ecosystems, where they exert strong influences on metabolism and material cycling. At the same time, metabolic theory proposes endogenous thermal control independent of resource supply. To address the relative importance of exogenous and endogenous influences, we quantified spatial and temporal variation in ecosystem metabolism and nitrogen (N) uptake using seasonal releases of 15N as nitrate in six streams differing in riparian-stream interaction and metabolic character. Nitrate removal was quantified using a nutrient spiraling approach based on measurements of downstream decline in 15N flux. Respiration (R) and gross primary production (GPP) were measured with whole-stream diel oxygen budgets. Uptake and metabolism metrics were addressed as z scores relative to site means to assess temporal variation. In open-canopied streams, areal uptake (U; microg N x m(-2) x s(-1)) was closely related to GPP, metabolic rates increased with temperature, and R was accurately predicted by metabolic scaling relationships. In forested streams, N spiraling was not related to GPP; instead, uptake velocity (v(f); mm/s) was closely related to R. In contrast to open-canopied streams, N uptake and metabolic activity were negatively correlated to temperature and poorly described by scaling laws. We contend that streams differ along a gradient of exogenous and endogenous control that relates to the relative influences of resource subsidies and in-stream energetics as determinants of seasonal patterns of metabolism and N cycling. Our research suggests that temporal variation in the propagation of ecological influence between adjacent systems generates phases when ecosystems are alternatively characterized as endogenously and exogenously controlled.

Using rabies virus vaccine strain SRV9 as viral vector to express exogenous gene.

PubMed

Wang, Hualei; Jin, Hongli; Feng, Na; Zheng, Xuexing; Li, Ling; Qi, Yinglin; Liang, Meng; Zhao, Yongkun; Wang, Tiecheng; Gao, Yuwei; Tu, Changchun; Jin, Ningyi; Yang, Songtao; Xia, Xianzhu

2015-04-01

Rabies virus (RABV) can cause a fatal neurological disease in human and animals, and vaccines were generally applied for the immunoprophylaxis of rabies. Here, a recombinant viral vector carrying the exogenous gene expression component between phosphoprotein (P) and matrix protein (M) genes of RABV was constructed based on the vaccine strain SRV9 used in China. To develop a reverse genetic system, the full-length cDNA plasmids of SRV9 were constructed using the eukaryotic expression vector pCI or pcDNA3.1(+). However, recovery efficiency based on the pcDNA3.1 vector was significantly higher than that of the pCI vector. The exogenous gene expression component PE-PS-BsiWI-PmeI or PS-BsiWI-PmeI-PE was introduced in different locations between the P and M genes of SRV9. When the enhanced green fluorescent protein (eGFP) was used as a reporter gene, both locations could rescue recombinant RABV (rRABV) expressing eGFP with high efficiency. Characterization of rRABV expressing eGFP in vitro revealed that its growth was similar to that of the parental virus. Animal experiments showed that rRABV expressing eGFP could replicate and express eGFP in the brains of suckling mice. Furthermore, rRABV of SRV9 was nonpathogenic for 3-week-old mice and could be cleared from the central nervous system at 5 days post-inoculation. Our results showed that the recombinant SRV9 virus could be used as a useful viral vector for exogenous gene expression.

Leydig Cell Aging and Hypogonadism

PubMed Central

Beattie, M.C.; Adekola, L.; Papadopoulos, V.; Chen, H.; Zirkin, B.R.

2015-01-01

Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences. PMID:25700847

Distribution and mobility of exogenous copper as influenced by aging and components interactions in three Chinese soils.

PubMed

Shi, Hanzhi; Li, Qi; Chen, Wenli; Cai, Peng; Huang, Qiaoyun

2018-04-01

Copper contamination of soils is a global environmental problem. Soil components (organic matter, clay minerals, and microorganisms) and retention time can govern the adsorption, fixation, and distribution of copper. This study evaluated the interaction effects of soil components and aging on the distribution of exogenous copper. Three typical Chinese soils (Ultisol, Alfisol, and Histosol) were collected from Hunan, Henan, and Heilongjiang Provinces. Soils were incubated with rice straw (RS) and engineered bacteria (Pseudomonas putida X4/pIME) in the presence of exogenous copper for 12 months. Sequential extraction was employed to obtain the distribution of Cu species in soils, and the mobility factors of Cu were calculated. The relationships between soil properties and Cu fractions were analyzed with stepwise multiple linear regression. The results show that organic carbon plays a more important role in shaping the distribution of relatively mobile Cu, and iron oxides can be more critical in stabilizing Cu species in soils. Our results suggest that organic matter is the most important factor influencing copper partitioning in Ultisols, while iron oxides are more significant in Alfisols. The mobility of exogenous Cu in soils depends largely on organic carbon, amorphous Fe, and aging. The introduction of both rice straw and rice straw + engineered bacteria enhanced the stabilization of Cu in all the three soils during aging process. The introduction of bacteria could reduce copper mobility, which was indicated by the lowest mobility factors of Cu for the treatment with bacteria in Black, Red, and Cinnamon soils at the first 4, 8, and 8 months, respectively. Different measures should be taken into account regarding the content of organic matter and iron oxides depending on soil types for the risk assessment and remediation of Cu-contaminated soils.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

Pseudo-Outbreak of Lecanicillium and Acremonium Species in Orthopedic Surgery Patients

PubMed Central

Neal, Carolyn O. S.; Deak, Eszter; Chang, Loretta S.; Gilmartin, Heather; Gade, Lalitha; Imanishi, Maho; Price, Connie; Chiller, Tom; Balajee, S. Arunmozhi

2012-01-01

Acremonium species cause a variety of human infections, while Lecanicillium species have not been reported as human pathogens. We describe a pseudo-outbreak involving both organisms, highlighting the role and limitations of molecular methods in the characterization of rare fungal isolates. Repeated isolation of these fungi from patient tissue samples raises concerns about exogenous contamination in the hospital environment. PMID:23015668

Exogenous near-infrared fluorophores and their applications in cancer diagnosis: biological and clinical perspectives.

PubMed

Zhang, Hua; Uselman, Ryan R; Yee, Douglas

2011-05-01

Near-infrared fluorescent (NIRF) imaging is a rapidly growing research field which has the potential to be an important imaging modality in cancer diagnosis. Various exogenous NIR fluorophores have been developed for the technique, including small molecule fluorophores and nanoparticles. NIRF imaging has been used in animal models for the detection of cancer overthe last twenty years and has in recent years been used in human clinical trials. This article describes the types and characteristics of exogenous fluorophores available for in vivo fluorescent cancer imaging. The article also discusses the progression of NIRF cancer imaging over recent years and its future challenges, from both a biological and clinical perspective. in The review also looks at its application for lymph node mapping, tumor targeting and characterization, and tumor margin definition for surgical guidance. NIRF imaging is not in routine clinical cancer practice; yet, the authors predict that techniques using NIR fluorophores for tumor margin definition and lymph node mapping will enter clinical practice in the near future. The authors also anticipate that NIRF imaging research will lead to the development of flurophores with 'high brightness' that will overcome the limited penetration of this modality and be better suited for non invasive tumor targeting.

Proteomic Response and Quality Maintenance in Postharvest Fruit of Strawberry (Fragaria × ananassa) to Exogenous Cytokinin.

PubMed

Li, Li; Li, Dongdong; Luo, Zisheng; Huang, Xinhong; Li, Xihong

2016-06-01

The limitations in current understanding of the molecular mechanisms underlying fruit response to the application of plant growth regulators have increasingly become major challenges in improvement of crop quality. This study aimed to evaluate the response of strawberry to the preharvest application of exogenous cytokinin known as forchlorfenuron (CPPU). Postharvest internal and physiological quality attributes were characterized following storage under different conditions. Hierarchical clustering analysis via a label-free proteomic quantitative approach identified a total of 124 proteins in strawberries across all treatments. The expression profiles of both proteins and genes spanned the ranged role of cytokinin involved in primary and secondary metabolism, stress response, and so on. Eighty-eight proteins and fifty-six proteins were significantly regulated immediately at harvest and after storage, respectively. In general, the glycolysis in strawberry was only regulated by CPPU before storage; in addition to the accelerated photosynthesis and acid metabolism, CPPU application maintained higher capacity of resistance in strawberry to stress stimuli after storage, in comparison to control. Nevertheless, the volatile biosynthesis in strawberry has been suppressed by exogenous CPPU. Novel cytokinin response proteins and processes were identified in addition to the main transcriptomic expression to gain insights into the phytohormone control of fruit postharvest quality.

Characterization of a wheat (Triticum aestivum L.) expansin gene, TaEXPB23, involved in the abiotic stress response and phytohormone regulation.

PubMed

Han, Yang yang; Li, Ai xiu; Li, Feng; Zhao, Mei rong; Wang, Wei

2012-05-01

Expansins are proteins that are generally accepted to be key regulators of cell wall extension and plant growth. We examined the expression pattern of TaEXPB23, a wheat (Triticum aestivum L.) expansin gene, under exogenous phytohormone and abiotic stress treatments. In addition, we evaluated its function in the tolerance to salt stress and high temperature (HT) by overexpressing it in transgenic tobacco plants. In subcellular localization assays, TaEXPB23 localized to the cell wall. Expression analysis demonstrated that the transcription pattern of TaEXPB23 corresponded to wheat coleoptile growth. Real-time RT-PCR analysis revealed that TaEXPB23 transcript expression was upregulated by exogenous methyl jasmonate (MeJA) and salt stress, but downregulated by exogenous gibberellins (GA₃), ethylene (ET), indole-3-acetic acid (IAA) and α-naphthlcetic acid (NAA). Overexpression of TaEXPB23 in tobacco (tabacum) conferred tolerance to salt stress by enhancing water retention ability (WRA) and decreasing osmotic potential (OP). However, transgenic plants overexpressing TaEXPB23 did not show any improvement in the tolerance to HT stress. These results suggested that TaEXPB23 is regulated by phytohormones and is involved in the regulation of salt stress tolerance. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Estimation of single-kidney glomerular filtration rate without exogenous contrast agent.

PubMed

He, Xiang; Aghayev, Ayaz; Gumus, Serter; Ty Bae, K

2014-01-01

Measurement of single-kidney filtration fraction and glomerular filtration rate (GFR) without exogenous contrast is clinically important to assess renal function and pathophysiology, especially for patients with comprised renal function. The objective of this study is to develop a novel MR-based tool for noninvasive quantification of renal function using conventional MR arterial spin labeling water as endogenous tracer. The regional differentiation of the arterial spin labeling water between the glomerular capsular space and the renal parenchyma was characterized and measured according to their MR relaxation properties (T1ρ or T2 ), and applied to the estimation of filtration fraction and single-kidney GFR. The proposed approach was tested to quantify GFR in healthy volunteers at baseline and after a protein-loading challenge. Biexponential decay of the cortical arterial spin labeling water MR signal was observed. The major component decays the same as parenchyma water; the minor component decays much slower as expected from glomerular ultra-filtrates. The mean single-kidney GFR was estimated to be 49 ± 9 mL/min at baseline and increased by 28% after a protein-loading challenge. We developed an arterial spin labeling-based MR imaging method that allows us to estimate renal filtration fraction and singe-kidney GFR without use of exogenous contrast. Copyright © 2013 Wiley Periodicals, Inc.

Binary versus non-binary information in real time series: empirical results and maximum-entropy matrix models

NASA Astrophysics Data System (ADS)

Almog, Assaf; Garlaschelli, Diego

2014-09-01

The dynamics of complex systems, from financial markets to the brain, can be monitored in terms of multiple time series of activity of the constituent units, such as stocks or neurons, respectively. While the main focus of time series analysis is on the magnitude of temporal increments, a significant piece of information is encoded into the binary projection (i.e. the sign) of such increments. In this paper we provide further evidence of this by showing strong nonlinear relations between binary and non-binary properties of financial time series. These relations are a novel quantification of the fact that extreme price increments occur more often when most stocks move in the same direction. We then introduce an information-theoretic approach to the analysis of the binary signature of single and multiple time series. Through the definition of maximum-entropy ensembles of binary matrices and their mapping to spin models in statistical physics, we quantify the information encoded into the simplest binary properties of real time series and identify the most informative property given a set of measurements. Our formalism is able to accurately replicate, and mathematically characterize, the observed binary/non-binary relations. We also obtain a phase diagram allowing us to identify, based only on the instantaneous aggregate return of a set of multiple time series, a regime where the so-called ‘market mode’ has an optimal interpretation in terms of collective (endogenous) effects, a regime where it is parsimoniously explained by pure noise, and a regime where it can be regarded as a combination of endogenous and exogenous factors. Our approach allows us to connect spin models, simple stochastic processes, and ensembles of time series inferred from partial information.

Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

NASA Astrophysics Data System (ADS)

Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

2016-03-01

Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer.

Retinal input to efferent target amacrine cells in the avian retina

PubMed Central

Lindstrom, Sarah H.; Azizi, Nason; Weller, Cynthia; Wilson, Martin

2012-01-01

The bird visual system includes a substantial projection, of unknown function, from a midbrain nucleus to the contralateral retina. Every centrifugal, or efferent, neuron originating in the midbrain nucleus makes synaptic contact with the soma of a single, unique amacrine cell, the target cell (TC). By labeling efferent neurons in the midbrain we have been able to identify their terminals in retinal slices and make patch clamp recordings from TCs. TCs generate Na+ based action potentials triggered by spontaneous EPSPs originating from multiple classes of presynaptic neurons. Exogenously applied glutamate elicited inward currents having the mixed pharmacology of NMDA, kainate and inward rectifying AMPA receptors. Exogenously applied GABA elicited currents entirely suppressed by GABAzine, and therefore mediated by GABAA receptors. Immunohistochemistry showed the vesicular glutamate transporter, vGluT2, to be present in the characteristic synaptic boutons of efferent terminals, whereas the GABA synthetic enzyme, GAD, was present in much smaller processes of intrinsic retinal neurons. Extracellular recording showed that exogenously applied GABA was directly excitatory to TCs and, consistent with this, NKCC, the Cl− transporter often associated with excitatory GABAergic synapses, was identified in TCs by antibody staining. The presence of excitatory retinal input to TCs implies that TCs are not merely slaves to their midbrain input; instead, their output reflects local retinal activity and descending input from the midbrain. PMID:20650017

Variations in the patterns of soil organic carbon mineralization and microbial communities in response to exogenous application of rice straw and calcium carbonate.

PubMed

Feng, Shuzhen; Huang, Yuan; Ge, Yunhui; Su, Yirong; Xu, Xinwen; Wang, Yongdong; He, Xunyang

2016-11-15

The addition of exogenous inorganic carbon (CaCO3) and organic carbon has an important influence on soil organic carbon (SOC) mineralization in karst soil, but the microbial mechanisms underlying the SOC priming effect are poorly understood. We conducted a 100-day incubation experiment involving four treatments of the calcareous soil in southwestern China's karst region: control, (14)C-labeled rice straw addition, (14)C-labeled CaCO3 addition, and a combination of (14)C-labeled rice straw and CaCO3. Changes in soil microbial communities were characterized using denaturing gradient gel electrophoresis with polymerase chain reaction (PCR-DGGE) and real-time quantitative PCR (q-PCR). Both (14)C-rice straw and Ca(14)CO3 addition stimulated SOC mineralization, suggesting that organic and inorganic C affected SOC stability. Addition of straw alone had no significant effect on bacterial diversity; however, when the straw was added in combination with calcium carbonate, it had an inhibitory effect on bacterial and fungal diversity. At the beginning of the experimental period, exogenous additives increased bacterial abundance, although at the end of the 100-day incubation bacterial community abundance had gradually declined. Incubation time, exogenous input, and their interaction significantly affected SOC mineralization (in terms of priming and the cumulative amount of mineralization), microbial biomass carbon (MBC), and microbial community abundance and diversity. Moreover, the key factors influencing SOC mineralization were MBC, bacterial diversity, and soil pH. Overall, these findings support the view that inorganic C is involved in soil C turnover with the participation of soil microbial communities, promoting soil C cycling in the karst region. Copyright © 2016 Elsevier B.V. All rights reserved.

Exogenous carbonaceous matter in ancient martian sediments

NASA Astrophysics Data System (ADS)

Mojzsis, S. J.; Abramov, O.; Kereszturi, A.

2015-12-01

We re-evaluate the early evolution of an organic-matter rich (~10 wt. %) interplanetary dust particle flux to early Mars. Our work builds upon physical models that rely on plausible sources of exogenous debris and their dynamical rates of decay, the martian cratering record, and preservation of Noachian-Hesperian sedimentary units that have the potential to host organics. Post primary-accretionary scenarios that would have delivered abundant exogenous carbon to Mars can be imagined in two ways: a simple exponential decay with an approximately 100 Myr half-life, or as a "Sawtooth" timeline characterized by both faster-than-exponential decay from primary accretion and reduced total delivered mass. Indications are that a late bombardment spike was superposed on an otherwise broadly monotonic decline from primary accretion, of which two types are explored: a classical "Late Heavy Bombardment" (LHB) peak of impactors centered at ca. 3950 Ma and lasting 100 Myr, and a protracted bombardment typified by a sudden increase in impactor flux at ca. 4240-4100 Ma with a correspondingly longer decay time (400 Myr). Numerical models for each of the four bombardment scenarios explored in this work shows that exogenous organic matter could be a significant component of Noachian (ca. 4200-3700 Ma) and pre-Noachian (4500-4200 Ma) sediments. The discovery of organic-matter in martian sediments will be obfuscated by material of extra-areological origin. We predict that an earmark for the origin of this carbon would be correlated siderophile element abundances (e.g. Ni, Cr, and the platinoids). A time-dependent compositional relationship of C:HSEs would allow us to derive a chemochronology for pre-Hesperian (pre-3700 Ma) sedimentary units.

Leydig cell aging and hypogonadism.

PubMed

Beattie, M C; Adekola, L; Papadopoulos, V; Chen, H; Zirkin, B R

2015-08-01

Leydig cell testosterone (T) production is reduced with age, resulting in reduced serum T levels (hypogonadism). A number of cellular changes have been identified in the steroidogenic pathway of aged Leydig cells that are associated with reduced T formation, including reductions in luteinizing hormone (LH)-stimulated cAMP production, the cholesterol transport proteins steroidogenic acute regulatory (STAR) protein and translocator protein (TSPO), and downstream steroidogenic enzymes of the mitochondria and smooth endoplasmic reticulum. Many of the changes in steroid formation that characterize aged Leydig cells can be elicited by the experimental alteration of the redox environment of young cells, suggesting that changes in the intracellular redox balance may cause reduced T production. Hypogonadism is estimated to affect about 5 million American men, including both aged and young. This condition has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass, reduced bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Exogenous T administration is now used widely to elevate serum T levels in hypogonadal men and thus to treat symptoms of hypogonadism. However, recent evidence suggests that men who take exogenous T may face increased risk of stroke, heart attack, and prostate tumorigenesis. Moreover, it is well established that administered T can have suppressive effects on LH, resulting in lower Leydig cell T production, reduced intratesticular T concentration, and reduced spermatogenesis. This makes exogenous T administration inappropriate for men who wish to father children. There are promising new approaches to increase serum T by directly stimulating Leydig cell T production rather than by exogenous T therapy, thus potentially avoiding some of its negative consequences. Copyright © 2015 Elsevier Inc. All rights reserved.

[Innate immunity in neuroimmunological disorders].

PubMed

Miyake, Sachiko

2013-05-01

Exogeneous pathogen-associated molecular patterns and endogenous danger signals bind to pattern recognition receptors and activate innate immunity cells, leading to proinflammatory cytokine production and activation of acquired immue cells. These are important factors in the pathogenesis of autoimmune-mediated neuroimmunological disorders such as multiple sclerosis. Furthermore, recent advances in the study of innate immunity revealed that innate immunity is a major players in the pathogenesis of some neuroimmunological diseases such as Behçet's disease and herpes simplex virus encephalitis.

Effects of Melatonin on Anti-oxidative Systems and Photosystem II in Cold-Stressed Rice Seedlings

PubMed Central

Han, Qiao-Hong; Huang, Bo; Ding, Chun-Bang; Zhang, Zhong-Wei; Chen, Yang-Er; Hu, Chao; Zhou, Li-Jun; Huang, Yan; Liao, Jin-Qiu; Yuan, Shu; Yuan, Ming

2017-01-01

Melatonin (N-acetyl-5-methoxytryptamine) plays important role in multiple plant developmental processes and stress responses. We investigated the possible mediatory role of melatonin in growth, photosynthesis, and the response to cold stress in rice by using three different experiments: soaking seed; immersing roots, and spraying to leaves with 0, 20, or 100 μM melatonin. After 6 days of cold stress, the growth of rice seedlings was significantly inhibited, but this inhibition was alleviated by exogenous melatonin. Furthermore, exogenous melatonin pretreatment alleviated the accumulation of reactive oxygen species, malondialdehyde and cell death induced by cold stress. Melatonin pretreatment also relieved the stress-induced inhibitions to photosynthesis and photosystem II activities. Further investigations showed that, antioxidant enzyme activities and non-enzymatic antioxidant levels were increased by melatonin pretreatments. The treatment methods of seed soaking and root immersion were more effective in improving cold stress resistance than the spraying method. The results also indicated the dose-dependent response of melatonin on rice physiological, biochemical, and photosynthetic parameters. PMID:28553310

Conveying endogenous and exogenous signals: MAPK cascades in plant growth and defense.

PubMed

Zhang, Mengmeng; Su, Jianbin; Zhang, Yan; Xu, Juan; Zhang, Shuqun

2018-05-09

Mitogen-activated protein kinase (MAPK) cascades are key signaling modules downstream of receptors/sensors that perceive endogenous and exogenous stimuli such as hormones, peptide ligands, and pathogen-derived patterns/effectors. In this review, we summarize recent advances in the establishment of MAPK cascades as unified signaling modules downstream of receptor-like kinases (RLKs) and receptor-like proteins (RLPs) in plant growth and defense, the identification of components connecting the RLK/RLP receptor complexes to the MAPK cascades, and the interactions between MAPK and hormone signaling pathways. We also propose a set of criteria for defining the physiological substrates of plant MAPKs. With only a limited number of MAPK components, multiple functional pathways often share the same MAPK cascade. As a result, understanding the signaling specificity, which requires detailed information about the spatiotemporal expression of the components involved, their complex formation, and the consequence of substrate phosphorylation, is central to our study of MAPK functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Growth inhibition of Saccharomyces cerevisiae by the immunosuppressant leflunomide is due to the inhibition of uracil uptake via Fur4p.

PubMed

Fujimura, H

1998-10-01

The immunosuppressant leflunomide inhibits cytokine-stimulated proliferation of lymphoid cells in vitro and also inhibits the growth of the eukaryotic microorganism Saccharomyces cerevisiae. To elucidate the molecular mechanism of action of the drug, two yeast genes which suppress the anti-proliferative effect when present in multiple copies were cloned and designated MLF1 and MLF2 for multicopy suppressor of leflunomide sensitivity. DNA sequencing analysis revealed that the MLF1 gene is identical to the FUR4 gene, which encodes a uracil permease and functions to import uracil efficiently. The MLF2 was found to be identical to the URA3 gene. Excess exogenous uracil also overcomes the anti-proliferative effect of leflunomide on yeast cells. Uracil prototrophy also conferred resistance to leflunomide. Uracil uptake was inhibited by leflunomide. Thus, the growth inhibition by leflunomide seen in a S. cerevisiae ura3 auxotroph is due to the inhibition of the entry of exogenous uracil via the Fur4 uracil permease.

Environmental fatty acids enable emergence of infectious Staphylococcus aureus resistant to FASII-targeted antimicrobials

PubMed Central

Morvan, Claire; Halpern, David; Kénanian, Gérald; Hays, Constantin; Anba-Mondoloni, Jamila; Brinster, Sophie; Kennedy, Sean; Trieu-Cuot, Patrick; Poyart, Claire; Lamberet, Gilles; Gloux, Karine; Gruss, Alexandra

2016-01-01

The bacterial pathway for fatty acid biosynthesis, FASII, is a target for development of new anti-staphylococcal drugs. This strategy is based on previous reports indicating that self-synthesized fatty acids appear to be indispensable for Staphylococcus aureus growth and virulence, although other bacteria can use exogenous fatty acids to compensate FASII inhibition. Here we report that staphylococci can become resistant to the FASII-targeted inhibitor triclosan via high frequency mutations in fabD, one of the FASII genes. The fabD mutants can be conditional for FASII and not require exogenous fatty acids for normal growth, and can use diverse fatty acid combinations (including host fatty acids) when FASII is blocked. These mutants show cross-resistance to inhibitors of other FASII enzymes and are infectious in mice. Clinical isolates bearing fabD polymorphisms also bypass FASII inhibition. We propose that fatty acid-rich environments within the host, in the presence of FASII inhibitors, might favour the emergence of staphylococcal strains displaying resistance to multiple FASII inhibitors. PMID:27703138

Invasive fungal infections in endogenous Cushing's syndrome

PubMed Central

Scheffel, Rafael Selbach; Dora, José Miguel; Weinert, Letícia Schwerz; Aquino, Valério; Maia, Ana Luiza; Canani, Luis Henrique; Goldani, Luciano Z.

2010-01-01

Cushing's syndrome is a condition characterized by elevated cortisol levels that can result from either augmented endogenous production or exogenous administration of corticosteroids. The predisposition to fungal infections among patients with hypercortisolemia has been noted since Cushing's original description of the disease. We describe here a patient with endogenous Cushing's syndrome secondary to an adrenocortical carcinoma, who developed concomitant disseminated cryptococcosis and candidiasis in the course of his disease. PMID:24470886

Functional characterization of electron-transferring flavoprotein and its dehydrogenase required for fungal development and plant infection by the rice blast fungus

PubMed Central

Li, Ya; Zhu, Jindong; Hu, Jiexiong; Meng, Xiuli; Zhang, Qi; Zhu, Kunpeng; Chen, Xiaomin; Chen, Xuehang; Li, Guangpu; Wang, Zonghua; Lu, Guodong

2016-01-01

Electron-transferring flavoprotein (ETF) and its dehydrogenase (ETFDH) are highly conserved electron carriers which mainly function in mitochondrial fatty acid β oxidation. Here, we report the identification and characterization of ETF α and β subunit encoding genes (ETFA and ETFB) and ETFDH encoding gene (ETFDH) in the rice blast fungus Magnaporthe oryzae. It was demonstrated that, by impacting fatty acid metabolism, ETF and ETFDH mutations led to severe growth and conidiation defects, which could be largely rescued by exogenous acetate or carbonate. Furthermore, although conidium germination and appressorium formation appeared to be normal in ETF and ETFDH mutants, most appressoria failed to penetrate the host epidermis due to low turgor pressure. The few appressoria that succeeded in penetration were severely restricted in invasive growth and consequently failed to cause disease. Moreover, ETF mutant etfb− induced ROS accumulation in infected host cells and exogenous antioxidant GSH accelerated mutant invading growth without increasing the penetration rate. In addition, mutant etfb− displayed elevated lipid body accumulation and reduced ATP synthesis. Taken together, ETF and ETFDH play an important role in fungal development and plant infection in M. oryzae by regulation of fatty acid metabolism, turgor establishment and induction of host ROS accumulation. PMID:27113712

Functional characterization of electron-transferring flavoprotein and its dehydrogenase required for fungal development and plant infection by the rice blast fungus.

PubMed

Li, Ya; Zhu, Jindong; Hu, Jiexiong; Meng, Xiuli; Zhang, Qi; Zhu, Kunpeng; Chen, Xiaomin; Chen, Xuehang; Li, Guangpu; Wang, Zonghua; Lu, Guodong

2016-04-26

Electron-transferring flavoprotein (ETF) and its dehydrogenase (ETFDH) are highly conserved electron carriers which mainly function in mitochondrial fatty acid β oxidation. Here, we report the identification and characterization of ETF α and β subunit encoding genes (ETFA and ETFB) and ETFDH encoding gene (ETFDH) in the rice blast fungus Magnaporthe oryzae. It was demonstrated that, by impacting fatty acid metabolism, ETF and ETFDH mutations led to severe growth and conidiation defects, which could be largely rescued by exogenous acetate or carbonate. Furthermore, although conidium germination and appressorium formation appeared to be normal in ETF and ETFDH mutants, most appressoria failed to penetrate the host epidermis due to low turgor pressure. The few appressoria that succeeded in penetration were severely restricted in invasive growth and consequently failed to cause disease. Moreover, ETF mutant etfb(-) induced ROS accumulation in infected host cells and exogenous antioxidant GSH accelerated mutant invading growth without increasing the penetration rate. In addition, mutant etfb(-) displayed elevated lipid body accumulation and reduced ATP synthesis. Taken together, ETF and ETFDH play an important role in fungal development and plant infection in M. oryzae by regulation of fatty acid metabolism, turgor establishment and induction of host ROS accumulation.

Development and validation of an oxygen dissociation assay, a screening platform for discovering, and characterizing hemoglobin-oxygen affinity modifiers.

PubMed

Patel, Mira P; Siu, Vincent; Silva-Garcia, Abel; Xu, Qing; Li, Zhe; Oksenberg, Donna

2018-01-01

Hemoglobin (Hb) is a critical molecule necessary for all vertebrates to maintain aerobic metabolism. Hb-oxygen (O 2 ) affinity modifiers have been studied to address various diseases including sickle cell disease, hypoxemia, tumor hypoxia, and wound healing. However, drug development of exogenous Hb modifiers has been hindered by the lack of a technique to rapidly screen compounds for their ability to alter Hb-O 2 affinity. We have developed a novel screening assay based upon the spectral changes observed during Hb deoxygenation and termed it the oxygen dissociation assay (ODA). ODA allows for the quantitation of oxygenated Hb at given time points during Hb deoxygenation on a 96-well plate. This assay was validated by comparing the ability of 500 Hb modifiers to alter the Hb-O 2 affinity in the ODA vs the oxygen equilibrium curves obtained using the industry standard Hemox Analyzer instrument. A correlation ( R 2 ) of 0.7 indicated that the ODA has the potential to screen and identify potent exogenous Hb modifiers. In addition, it allows for concurrent comparison of compounds, concentrations, buffers, or pHs on the level of Hb oxygenation. With a cost-effective, simple, rapid, and highly adaptable assay, the ODA will allow researchers to rapidly characterize Hb-O 2 affinity modifiers.

Molecular characterization of Mycobacterium tuberculosis isolated in the State of Parana in southern Brazil.

PubMed

Malaghini, Marcelo; Brockelt, Sonia Regina; Burger, Marion; Kritski, Afrânio; Thomaz-Soccol, Vanete

2009-01-01

Sequence IS6110 has been successfully used throughout the world for characterizing the Mycobacterium tuberculosis lineages. The aim of this study was to obtain data about circulating strains of M. tuberculosis in patients from the State of Parana in southern Brazil. Sixty-two clinical specimens obtained from sputum, bronchial aspirate, biopsy and urine from 62 patients clinically diagnosed with tuberculosis and admitted to the SUS-Brazil - The Brazilian Centralized Health Service System - were genotyped by the mixed-linker PCR DNA fingerprinting technique. The analysis demonstrated that the number of copies of the IS6110 sequence per isolates varied from four to 13 bands, with an average number of 8.5. From this, 93% of the isolates presented multiple copies. Isolates with no copies of the IS6110 element were not observed. The genetic analysis by UPGMA grouped the 62 isolates by similarity into three different groups: the first group contained two strains, the second was composed of 23, and the third, a more heterogeneous group, contained 37 isolates. Only two isolates (3.2%) formed a cluster; in other words, they presented a pattern of polymorphism with similarity above 95%. Such findings suggest that in the State of Parana, illness predominantly develops through reactivation of the latent infection as opposed to exogenous transmission. The methodology used (mixed-linker PCR DNA fingerprinting) allowed for 93.5% differentiation of the isolates tested, and proved to be a powerful tool for differentiation in the molecular genotyping of M. tuberculosis.

Development of stereotactic mass spectrometry for brain tumor surgery.

PubMed

Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

2011-02-01

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

Pharmacological Effects of Niacin on Acute Hyperlipemia.

PubMed

la Paz, Sergio Montserrat-de; Bermudez, Beatriz; Naranjo, M Carmen; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2016-01-01

The well-known changes in modern lifestyle habits including over nutrition and physical inactivity have led to striking adverse effects on public health (e.g., obesity, diabetes, and metabolic syndrome) over recent decades. One noticeable consequence is exaggerated and prolonged state of postprandial hyperlipemia due to the ingestion of multiple fat-enriched meals during the course of a day. Postprandial (non-fasting) hyperlipemia is characterized by increased blood levels of exogenous triglycerides (TG) in the form of apolipoprotein (apo) B48-containing TG-rich lipoproteins (TRL), which have a causal role in the pathogenesis and progression of cardiovascular disease (CVD). The cardiovascular benefits of lifestyle modification (healthy diet and exercise) and conventional lipid-lowering therapies (e.g., statins, fibrates, and niacin) could involve their favourable effects on postprandial metabolism. Pharmacologically, niacin has been used as an athero-protective drug for five decades. Studies have since shown that niacin may decrease fasting levels of plasma verylow- density lipoproteins (VLDL), low-density lipoprotein cholesterol (LDL-C), and lipoprotein [a] (Lp[a]), while may increase high-density lipoprotein cholesterol (HDL-C). Herein, the purpose of this review was to provide an update on effects and mechanisms related to the pharmacological actions of niacin on acute hyperlipemia.

Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress

PubMed Central

Young, Regina M.; Ackerman, Daniel; Quinn, Zachary L.; Mancuso, Anthony; Gruber, Michaela; Liu, Liping; Giannoukos, Dionysios N.; Bobrovnikova-Marjon, Ekaterina; Diehl, J. Alan; Keith, Brian; Simon, M. Celeste

2013-01-01

Solid tumors exhibit heterogeneous microenvironments, often characterized by limiting concentrations of oxygen (O2), glucose, and other nutrients. How oncogenic mutations alter stress response pathways, metabolism, and cell survival in the face of these challenges is incompletely understood. Here we report that constitutive mammalian target of rapamycin complex 1 (mTORC1) activity renders hypoxic cells dependent on exogenous desaturated lipids, as levels of de novo synthesized unsaturated fatty acids are reduced under low O2. Specifically, we demonstrate that hypoxic Tsc2−/− (tuberous sclerosis complex 2−/−) cells deprived of serum lipids exhibit a magnified unfolded protein response (UPR) but fail to appropriately expand their endoplasmic reticulum (ER), leading to inositol-requiring protein-1 (IRE1)-dependent cell death that can be reversed by the addition of unsaturated lipids. UPR activation and apoptosis were also detected in Tsc2-deficient kidney tumors. Importantly, we observed this phenotype in multiple human cancer cell lines and suggest that cells committed to unregulated growth within ischemic tumor microenvironments are unable to balance lipid and protein synthesis due to a critical limitation in desaturated lipids. PMID:23699409

Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

PubMed Central

Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

2009-01-01

In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

Optical coherence tomography and computer-aided diagnosis of a murine model of chronic kidney disease

NASA Astrophysics Data System (ADS)

Wang, Bohan; Wang, Hsing-Wen; Guo, Hengchang; Anderson, Erik; Tang, Qinggong; Wu, Tongtong; Falola, Reuben; Smith, Tikina; Andrews, Peter M.; Chen, Yu

2017-12-01

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function over time. Histopathological analysis of the condition of glomeruli and the proximal convolutional tubules over time can provide valuable insights into the progression of CKD. Optical coherence tomography (OCT) is a technology that can analyze the microscopic structures of a kidney in a nondestructive manner. Recently, we have shown that OCT can provide real-time imaging of kidney microstructures in vivo without administering exogenous contrast agents. A murine model of CKD induced by intravenous Adriamycin (ADR) injection is evaluated by OCT. OCT images of the rat kidneys have been captured every week up to eight weeks. Tubular diameter and hypertrophic tubule population of the kidneys at multiple time points after ADR injection have been evaluated through a fully automated computer-vision system. Results revealed that mean tubular diameter and hypertrophic tubule population increase with time in post-ADR injection period. The results suggest that OCT images of the kidney contain abundant information about kidney histopathology. Fully automated computer-aided diagnosis based on OCT has the potential for clinical evaluation of CKD conditions.

Rice early flowering1, a CKI, phosphorylates DELLA protein SLR1 to negatively regulate gibberellin signalling.

PubMed

Dai, Cheng; Xue, Hong-Wei

2010-06-02

The plant hormone gibberellin (GA) is crucial for multiple aspects of plant growth and development. To study the relevant regulatory mechanisms, we isolated a rice mutant earlier flowering1, el1, which is deficient in a casein kinase I that has critical roles in both plants and animals. el1 had an enhanced GA response, consistent with the suppression of EL1 expression by exogenous GA(3). Biochemical characterization showed that EL1 specifically phosphorylates the rice DELLA protein SLR1, proving a direct evidence for SLR1 phosphorylation. Overexpression of SLR1 in wild-type plants caused a severe dwarf phenotype, which was significantly suppressed by EL1 deficiency, indicating the negative effect of SLR1 on GA signalling requires the EL1 function. Further studies showed that the phosphorylation of SLR1 is important for maintaining its activity and stability, and mutation of the candidate phosphorylation site of SLR1 results in the altered GA signalling. This study shows EL1 a novel and key regulator of the GA response and provided important clues on casein kinase I activities in GA signalling and plant development.

Rapid construction of capsid-modified adenoviral vectors through bacteriophage lambda Red recombination.

PubMed

Campos, Samuel K; Barry, Michael A

2004-11-01

There are extensive efforts to develop cell-targeting adenoviral vectors for gene therapy wherein endogenous cell-binding ligands are ablated and exogenous ligands are introduced by genetic means. Although current approaches can genetically manipulate the capsid genes of adenoviral vectors, these approaches can be time-consuming and require multiple steps to produce a modified viral genome. We present here the use of the bacteriophage lambda Red recombination system as a valuable tool for the easy and rapid construction of capsid-modified adenoviral genomes.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Identification of two CiGADs from Caragana intermedia and their transcriptional responses to abiotic stresses and exogenous abscisic acid.

PubMed

Ji, Jing; Zheng, Lingyu; Yue, Jianyun; Yao, Xiamei; Chang, Ermei; Xie, Tiantian; Deng, Nan; Chen, Lanzhen; Huang, Yuwen; Jiang, Zeping; Shi, Shengqing

2017-01-01

Glutamate decarboxylase (GAD), as a key enzyme in the γ -aminobutyric acid (GABA) shunt, catalyzes the decarboxylation of L-glutamate to form GABA. This pathway has attracted much interest because of its roles in carbon and nitrogen metabolism, stress responses, and signaling in higher plants. The aim of this study was to isolate and characterize genes encoding GADs from Caragana intermedia , an important nitrogen-fixing leguminous shrub. Two full-length cDNAs encoding GADs (designated as CiGAD1 and CiGAD2 ) were isolated and characterized. Multiple alignment and phylogenetic analyses were conducted to evaluate their structures and identities to each other and to homologs in other plants. Tissue expression analyses were conducted to evaluate their transcriptional responses to stress (NaCl, ZnSO 4 , CdCl 2 , high/low temperature, and dehydration) and exogenous abscisic acid. The CiGAD s contained the conserved PLP domain and calmodulin (CaM)-binding domain in the C-terminal region. The phylogenetic analysis showed that they were more closely related to the GADs of soybean, another legume, than to GADs of other model plants. According to Southern blotting analysis, CiGAD1 had one copy and CiGAD2 -related genes were present as two copies in C. intermedia . In the tissue expression analyses, there were much higher transcript levels of CiGAD2 than CiGAD1 in bark, suggesting that CiGAD2 might play a role in secondary growth of woody plants. Several stress treatments (NaCl, ZnSO 4 , CdCl 2 , high/low temperature, and dehydration) significantly increased the transcript levels of both CiGAD s, except for CiGAD2 under Cd stress. The CiGAD1 transcript levels strongly increased in response to Zn stress (74.3-fold increase in roots) and heat stress (218.1-fold increase in leaves). The transcript levels of both CiGAD s significantly increased as GABA accumulated during a 24-h salt treatment. Abscisic acid was involved in regulating the expression of these two CiGAD s under salt stress. This study showed that two CiGAD s cloned from C. intermedia are closely related to homologs in another legume, soybean. CiGAD2 expression was much higher than that of CiGAD1 in bark, indicating that CiGAD2 might participate in the process of secondary growth in woody plants. Multiple stresses, interestingly, showed that Zn and heat stresses had the strongest effects on CiGAD1 expression, suggesting that CiGAD1 plays important roles in the responses to Zn and heat stresses. Additionally, these two genes might be involved in ABA dependent pathway during stress. This result provides important information about the role of GAD s in woody plants' responses to environmental stresses.

Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of Inflammation in Chickens

PubMed Central

Garrido, Damien; Chanteloup, Nathalie K.; Trotereau, Angélina; Lion, Adrien; Bailleul, Geoffrey; Esnault, Evelyne; Trapp, Sascha; Quéré, Pascale; Schouler, Catherine; Guabiraba, Rodrigo

2017-01-01

Lipid mediators are known to play important roles in the onset and resolution phases of the inflammatory response in mammals. The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their functions are still poorly characterized, and the role of PAF as an inflammatory mediator has not yet been investigated. In the present study we demonstrate that primary chicken macrophages express PAFR and lysophosphatidylcholine acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during inflammation. Also, exogenous PAF treatment induces intracellular calcium increase, reactive oxygen species release, and increased phagocytosis by primary chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes to the Escherichia coli lipopolysaccharide (LPS)-induced pro-inflammatory response and boosts the macrophage response to E. coli LPS via phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated intracellular signaling pathways. Exogenous PAF treatment also increases avian pathogenic E. coli intracellular killing by chicken macrophages, and PAFR and LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary colibacillosis. Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). In addition to these vascular phenomena, PAF boosts the chAEC inflammatory response to bacteria-associated molecular patterns in a PAFR-dependent manner. In conclusion, we identified PAF as an inflammation amplifier in chicken macrophages and ECs, which suggests that PAF could play important roles in the endothelium-innate immunity interface in birds during major bacterial infectious diseases such as colibacillosis. PMID:29326957

Cholera toxin B protein in transgenic tomato fruit induces systemic immune response in mice.

PubMed

Jiang, Xiao-Ling; He, Zhu-Mei; Peng, Zhi-Qiang; Qi, Yu; Chen, Qing; Yu, Shou-Yi

2007-04-01

Cholera toxin B (CTB) subunit is a well-characterized antigen against cholera. Transgenic plants can offer an inexpensive and safe source of edible CTB vaccine and may be one of the best candidates for the production of plant vaccines. The present study aimed to develop transgenic tomato expressing CTB protein, especially in the ripening tomato fruit under the control of the tomato fruit-specific E8 promoter by using Agrobacterium-mediated transformation. Transgenic plants were selected using PCR and Southern blot analysis. Exogenous protein extracted from leaf, stem, and fruit tissues of transgenic plants was detected by ELISA and Western blot analysis, showing specific expression in the ripening fruit, with the highest amount of CTB protein being 0.081% of total soluble protein. Gavage of mice with ripe transgenic tomato fruits induced both serum and mucosal CTB specific antibodies. These results demonstrate the immunogenicity of the CTB protein in transgenic tomato and provide a considerable basis for exploring the utilization of CTB in the development of tomato-based edible vaccine against cholera. The rCTB antigen resulted in much lower antibody titers than an equal amount of exogenous CTB in transgenic fruits, suggesting the protective effect of the fibrous tissue of the fruit to the exogenous CTB protein against the degradation of protease in the digestive tracts of mice.

Climate effects and feedback structure determining weed population dynamics in a long-term experiment.

PubMed

Lima, Mauricio; Navarrete, Luis; González-Andujar, José Luis

2012-01-01

Pest control is one of the areas in which population dynamic theory has been successfully applied to solve practical problems. However, the links between population dynamic theory and model construction have been less emphasized in the management and control of weed populations. Most management models of weed population dynamics have emphasized the role of the endogenous process, but the role of exogenous variables such as climate have been ignored in the study of weed populations and their management. Here, we use long-term data (22 years) on two annual weed species from a locality in Central Spain to determine the importance of endogenous and exogenous processes (local and large-scale climate factors). Our modeling study determined two different feedback structures and climate effects in the two weed species analyzed. While Descurainia sophia exhibited a second-order feedback and low climate influence, Veronica hederifolia was characterized by a first-order feedback structure and important effects from temperature and rainfall. Our results strongly suggest the importance of theoretical population dynamics in understanding plant population systems. Moreover, the use of this approach, discerning between the effect of exogenous and endogenous factors, can be fundamental to applying weed management practices in agricultural systems and to controlling invasive weedy species. This is a radical change from most approaches currently used to guide weed and invasive weedy species managements.

Climate Effects and Feedback Structure Determining Weed Population Dynamics in a Long-Term Experiment

PubMed Central

Lima, Mauricio; Navarrete, Luis; González-Andujar, José Luis

2012-01-01

Pest control is one of the areas in which population dynamic theory has been successfully applied to solve practical problems. However, the links between population dynamic theory and model construction have been less emphasized in the management and control of weed populations. Most management models of weed population dynamics have emphasized the role of the endogenous process, but the role of exogenous variables such as climate have been ignored in the study of weed populations and their management. Here, we use long-term data (22 years) on two annual weed species from a locality in Central Spain to determine the importance of endogenous and exogenous processes (local and large-scale climate factors). Our modeling study determined two different feedback structures and climate effects in the two weed species analyzed. While Descurainia sophia exhibited a second-order feedback and low climate influence, Veronica hederifolia was characterized by a first-order feedback structure and important effects from temperature and rainfall. Our results strongly suggest the importance of theoretical population dynamics in understanding plant population systems. Moreover, the use of this approach, discerning between the effect of exogenous and endogenous factors, can be fundamental to applying weed management practices in agricultural systems and to controlling invasive weedy species. This is a radical change from most approaches currently used to guide weed and invasive weedy species managements. PMID:22272362

[A unique case of secondary takotsubo syndrome].

PubMed

Arcari, Luca; Limite, Luca Rosario; Autore, Camillo; Volpe, Massimo; Musumeci, Maria Beatrice

2018-04-01

Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by transient systolic left ventricular dysfunction frequently preceded by stressful events. It typically affects postmenopausal women without angiographic evidence of obstructive coronary artery disease. We report here an uncommon occurrence of secondary TTS in a male with coronary artery disease after exogenous catecholamine administration and pacemaker implantation. This unexpected case suggests that, in such clinical scenario, a TTS diagnosis might be considered even in unsuspected individuals.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos

PubMed Central

2012-01-01

Background Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. Methods Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. Results The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). Conclusions Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner. PMID:22776023

Exogenous Melatonin Mitigates Photoinhibition by Accelerating Non-photochemical Quenching in Tomato Seedlings Exposed to Moderate Light during Chilling

PubMed Central

Ding, Fei; Wang, Meiling; Liu, Bin; Zhang, Shuoxin

2017-01-01

Melatonin plays an important role in tolerance to multiple stresses in plants. Recent studies have shown that melatonin relieves photoinhibition in plants under cold stress; however, the mechanisms are not fully understood. Non-photochemical quenching (NPQ) is a key process thermally dissipating excess light energy that plants employ as a protective mechanism to prevent the over reduction of photosystem II. Here, we report the effects of exogenous melatonin on NPQ and mitigation of photoinhibition in tomato seedlings exposed to moderate light during chilling. In response to moderate light during chilling, the maximum quantum yield (Fv/Fm) and the effective photochemical efficiency (F′v/F′m) of PSII were both substantially reduced, showing severe photoinhibition in tomato seedlings, whereas exogenous application of melatonin effectively alleviated the photoinhibition. Further experiment showed that melatonin accelerated the induction of NPQ in response to moderate light and maintained higher level of NPQ upon longer exposure to light during chilling. Consistent with the increased NPQ was the elevated de-epoxidation state of xanthophyll pigments in melatonin-pretreated seedlings exposed to light during chilling. Enzyme activity assay showed that violaxanthin de-epoxidase (VDE), which catalyzes the de-epoxidation reaction in the xanthophyll cycle, was activated by light and the activity was further enhanced by application of melatonin. Further analysis revealed that melatonin induced the expression of VDE gene in tomato seedlings under moderate light and chilling conditions. Ascorbic acid is an essential cofactor of VDE and the level of it was found to be increased in melatonin-pretreated seedlings. Feeding tomato seedlings with dithiothreitol, an inhibitor of VDE, blocked the effects of melatonin on the de-epoxidation state of xanthophyll pigments and the induction of NPQ. Collectively, these results suggest that exogenous melatonin mitigates photoinhibition by accelerating NPQ through the stimulation of VDE activity and the enhancement of de-epoxidation state of xanthophyll pigments. PMID:28265283

Exogenous Melatonin Mitigates Photoinhibition by Accelerating Non-photochemical Quenching in Tomato Seedlings Exposed to Moderate Light during Chilling.

PubMed

Ding, Fei; Wang, Meiling; Liu, Bin; Zhang, Shuoxin

2017-01-01

Melatonin plays an important role in tolerance to multiple stresses in plants. Recent studies have shown that melatonin relieves photoinhibition in plants under cold stress; however, the mechanisms are not fully understood. Non-photochemical quenching (NPQ) is a key process thermally dissipating excess light energy that plants employ as a protective mechanism to prevent the over reduction of photosystem II. Here, we report the effects of exogenous melatonin on NPQ and mitigation of photoinhibition in tomato seedlings exposed to moderate light during chilling. In response to moderate light during chilling, the maximum quantum yield (Fv/Fm) and the effective photochemical efficiency (F'v/F'm) of PSII were both substantially reduced, showing severe photoinhibition in tomato seedlings, whereas exogenous application of melatonin effectively alleviated the photoinhibition. Further experiment showed that melatonin accelerated the induction of NPQ in response to moderate light and maintained higher level of NPQ upon longer exposure to light during chilling. Consistent with the increased NPQ was the elevated de-epoxidation state of xanthophyll pigments in melatonin-pretreated seedlings exposed to light during chilling. Enzyme activity assay showed that violaxanthin de-epoxidase (VDE), which catalyzes the de-epoxidation reaction in the xanthophyll cycle, was activated by light and the activity was further enhanced by application of melatonin. Further analysis revealed that melatonin induced the expression of VDE gene in tomato seedlings under moderate light and chilling conditions. Ascorbic acid is an essential cofactor of VDE and the level of it was found to be increased in melatonin-pretreated seedlings. Feeding tomato seedlings with dithiothreitol, an inhibitor of VDE, blocked the effects of melatonin on the de-epoxidation state of xanthophyll pigments and the induction of NPQ. Collectively, these results suggest that exogenous melatonin mitigates photoinhibition by accelerating NPQ through the stimulation of VDE activity and the enhancement of de-epoxidation state of xanthophyll pigments.

[Effect of exogenous sucrose on growth and active ingredient content of licorice seedlings under salt stress conditions].

PubMed

Liu, Fu-zhi; Yang, Jun

2015-11-01

Licorice seedlings were taken as experimental materials, an experiment was conducted to study the effects of exogenous sucrose on growth and active ingredient content of licorice seedlings under NaCl stress conditions. The results of this study showed that under salt stress conditions, after adding a certain concentration of exogenous sucrose, the licorice seedlings day of relative growth rate was increasing, and this stress can be a significant weakening effect, indicating that exogenous sucrose salt stress-relieving effect. The total flavonoids and phenylalanine ammonia lyase (PAL) activity were significantly increased, the exogenous sucrose can mitigated the seedling roots under salt stress, the licorice flavonoid content in the enhanced growth was largely due to the activity of PAL an increased, when the concentration of exogenous sucrose wae 10 mmol x L(-1), PAL activity reaching a maximum, when the concentration of exogenous sucrose was 15 mmol x L(-1), PAL activity turned into a downward trend, the results indicating that this mitigation has concentration effect. After applying different concentrations of exogenous sugar, the contents of liquiritin changes with the change of flavonoids content was similar. After applying different concentrations of exogenous sucrose, the content of licorice acid under salt stress was higher than the levels were not reached during salt stress, the impact of exogenous sucrose concentration gradient of licorice acid accumulation was not obvious.

Update rules and interevent time distributions: slow ordering versus no ordering in the voter model.

PubMed

Fernández-Gracia, J; Eguíluz, V M; San Miguel, M

2011-07-01

We introduce a general methodology of update rules accounting for arbitrary interevent time (IET) distributions in simulations of interacting agents. We consider in particular update rules that depend on the state of the agent, so that the update becomes part of the dynamical model. As an illustration we consider the voter model in fully connected, random, and scale-free networks with an activation probability inversely proportional to the time since the last action, where an action can be an update attempt (an exogenous update) or a change of state (an endogenous update). We find that in the thermodynamic limit, at variance with standard updates and the exogenous update, the system orders slowly for the endogenous update. The approach to the absorbing state is characterized by a power-law decay of the density of interfaces, observing that the mean time to reach the absorbing state might be not well defined. The IET distributions resulting from both update schemes show power-law tails.

Metastable Pluripotent States in NOD Mouse Derived ES Cells

PubMed Central

Hanna, Jacob; Markoulaki, Styliani; Mitalipova, Maisam; Cheng, Albert W.; Cassady, John P.; Staerk, Judith; Carey, Bryce W.; Lengner, Christopher J.; Foreman, Ruth; Love, Jennifer; Gao, Qing; Kim, Jongpil; Jaenisch, Rudolf

2009-01-01

Embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of blastocysts, whereas epiblast stem cells (EpiSCs) are derived from the post-implantation epiblast and display a restricted developmental potential. Here we characterize pluripotent states in the non-obese diabetic (NOD) mouse strain, which prior to this study was considered “non-permissive” for ES cell derivation. We find that NOD stem cells can be stabilized by providing constitutive expression of Klf4 or c-Myc or small molecules that can replace these factors during in vitro reprogramming. The NOD ES and iPS cells appear “metastable”, as they acquire an alternative EpiSC-like identity after removal of the exogenous factors, while their reintroduction converts the cells back to ICM-like pluripotency. Our findings suggest that stem cells from different genetic backgrounds can assume distinct states of pluripotency in vitro, the stability of which is regulated by endogenous genetic determinants and can be modified by exogenous factors. PMID:19427283

Remote sensing of gene expression in Planta: transgenic plants as monitors of exogenous stress perception in extraterrestrial environments

NASA Technical Reports Server (NTRS)

Manak, Michael S.; Paul, Anna-Lisa; Sehnke, Paul C.; Ferl, Robert J.

2002-01-01

Transgenic arabidopsis plants containing the alcohol dehydrogenase (Adh) gene promoter fused to the green fluorescent protein (GFP) reporter gene were developed as biological sensors for monitoring physiological responses to unique environments. Plants were monitored in vivo during exposure to hypoxia, high salt, cold, and abcissic acid in experiments designed to characterize the utility and responses of the Adh/GFP biosensors. Plants in the presence of environmental stimuli that induced the Adh promoter responded by expressing GFP, which in turn generated a detectable fluorescent signal. The GFP signal degraded when the inducing stimulus was removed. Digital imaging of the Adh/GFP plants exposed to each of the exogenous stresses demonstrated that the stress-induced gene expression could be followed in real time. The experimental results established the feasibility of using a digital monitoring system for collecting gene expression data in real time from Transgenic Arabidopsis Gene Expression System (TAGES) biosensor plants during space exploration experiments.

Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert.

PubMed

Lee, Geoffrey; Espirito Santo, Ana Isabel; Zwingenberger, Stefan; Cai, Lawrence; Vogl, Thomas; Feldmann, Marc; Horwood, Nicole J; Chan, James K; Nanchahal, Jagdeep

2018-05-08

A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1 -/- mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G 0 to G Alert HMGB1 also transitions human stem and progenitor cells to G Alert Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery. Copyright © 2018 the Author(s). Published by PNAS.

Hemin offers neuroprotection through inducing exogenous neuroglobin in focal cerebral hypoxic-ischemia in rats

PubMed Central

Song, Xue; Xu, Rui; Xie, Fei; Zhu, Haiyuan; Zhu, Ji; Wang, Xin

2014-01-01

Objective: To investigate the inducible effect of hemin on exogenous neuroglobin (Ngb) in focal cerebral hypoxic-ischemia in rats. Methods: 125 healthy SD rats were randomly divided into five groups: sham-operation control group, operation group, hemin treatment group, exogenous Ngb treatment group, and hemin and exogenous Ngb joint treatment group. Twenty-four hours after focal cerebral hypoxic-ischemia, Ngb expression was evaluated by immunocytochemistry, RT-PCR, and western blot analyses, while the brain water content and infarct volume were examined. Results: Immunocytochemistry, RT-PCR, and western blot analyses showed more pronounced Ngb expression in the hemin and exogenous Ngb joint operation group than in the hemin or exogenous Ngb individual treatment groups, thus producing significant differences in brain water content and infarct volume (p < 0.05). Conclusions: Hemin may be beneficial in protecting against focal cerebral hypoxic-ischemia through inducing the expression of exogenous Ngb. PMID:24966924

Use of Exogenous Testosterone for the Treatment of Male Factor Infertility: A Survey of Nigerian Doctors.

PubMed

Omisanjo, Olufunmilade Akinfolarin; Ikuerowo, Stephen Odunayo; Abdulsalam, Moruf Adekunle; Ajenifuja, Sheriff Olabode; Shittu, Khadijah Adebisi

2017-01-01

Though exogenous testosterone is known for its contraceptive effects in men, it is sometimes prescribed by medical practitioners for the treatment of male factor infertility in the mistaken belief that exogenous testosterone improves sperm count. The aim of this study was to evaluate the scope of testosterone use in the treatment of male factor infertility by medical practitioners in Lagos, Nigeria. A survey using a structured questionnaire was carried out amongst doctors attending a regular Continuing Medical Education (CME) programme in Lagos, Nigeria. There were 225 respondents. Most of the respondents (69.8%, n = 157) indicated that exogenous testosterone increases sperm count. Only 22 respondents (9.8%) indicated (correctly) that exogenous testosterone decreases sperm count. Seventy-seven respondents (34.2%) had prescribed some form of exogenous testosterone in the treatment of male factor infertility. The vast majority of respondents who had prescribed testosterone (81.8%, n = 63) thought exogenous testosterone increases sperm count. There was no statistically significant difference in the pattern of prescription across the respondents' specialty ( p = 0.859) or practice type ( p = 0.747). The misuse of exogenous testosterone for the treatment of male infertility was common amongst the respondents, with most of them wrongly believing that exogenous testosterone increases sperm count.

Exogenous fatty acid metabolism in bacteria.

PubMed

Yao, Jiangwei; Rock, Charles O

2017-10-01

Bacterial type II fatty acid synthesis (FASII) is a target for novel antibiotic development. All bacteria encode for mechanisms to incorporate exogenous fatty acids, and some bacteria can use exogenous fatty acids to bypass FASII inhibition. Bacteria encode three different mechanisms for activating exogenous fatty acids for incorporation into phospholipid synthesis. Exogenous fatty acids are converted into acyl-CoA in Gammaproteobacteria such as E. coli. Acyl-CoA molecules constitute a separate pool from endogenously synthesized acyl-ACP. Acyl-CoA can be used for phospholipid synthesis or broken down by β-oxidation, but cannot be used for lipopolysaccharide synthesis. Exogenous fatty acids are converted into acyl-ACP in some Gram-negative bacteria. The resulting acyl-ACP undergoes the same fates as endogenously synthesized acyl-ACP. Exogenous fatty acids are converted into acyl-phosphates in Gram-positive bacteria, and can be used for phospholipid synthesis or become acyl-ACP. Only the order Lactobacillales can use exogenous fatty acids to bypass FASII inhibition. FASII shuts down completely in presence of exogenous fatty acids in Lactobacillales, allowing Lactobacillales to synthesize phospholipids entirely from exogenous fatty acids. Inhibition of FASII cannot be bypassed in other bacteria because FASII is only partially down-regulated in presence of exogenous fatty acid or FASII is required to synthesize essential metabolites such as β-hydroxyacyl-ACP. Certain selective pressures such as FASII inhibition or growth in biofilms can select for naturally occurring one step mutations that attenuate endogenous fatty acid synthesis. Although attempts have been made to estimate the natural prevalence of these mutants, culture-independent metagenomic methods would provide a better estimate. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Characterizing and modeling the dynamics of online popularity.

PubMed

Ratkiewicz, Jacob; Fortunato, Santo; Flammini, Alessandro; Menczer, Filippo; Vespignani, Alessandro

2010-10-08

Online popularity has an enormous impact on opinions, culture, policy, and profits. We provide a quantitative, large scale, temporal analysis of the dynamics of online content popularity in two massive model systems: the Wikipedia and an entire country's Web space. We find that the dynamics of popularity are characterized by bursts, displaying characteristic features of critical systems such as fat-tailed distributions of magnitude and interevent time. We propose a minimal model combining the classic preferential popularity increase mechanism with the occurrence of random popularity shifts due to exogenous factors. The model recovers the critical features observed in the empirical analysis of the systems analyzed here, highlighting the key factors needed in the description of popularity dynamics.

O-GlcNAcylation modulates PKA-CREB signaling in a manner specific to PKA catalytic subunit isoforms.

PubMed

Jin, Nana; Ma, Denglei; Gu, Jianlan; Shi, Jianhua; Xu, Xiaotao; Iqbal, Khalid; Gong, Cheng-Xin; Liu, Fei; Chu, Dandan

2018-02-26

O-GlcNAcylation is a post-translational modification of proteins. Protein kinase A (PKA)-cAMP response element binding protein (CREB) signaling plays critical roles in multiple biological processes. Isoforms α and β of PKA catalytic subunit (PKAc) and CREB are modified by O-GlcNAcylation. In the present study, we determined the role of O-GlcNAcylation in PKAc isoform-specific CREB signaling. We found that up-regulation of O-GlcNAcylation enhanced CREB phosphorylation, but suppressed CREB expression in exogenous PKAc isoform-unspecific manner. PKAc isoforms affected exogenous expression of OGT or OGA and protein O-GlcNAcylation differently. Up-regulation of O-GlcNAcylation did not significantly affect net PKAcα-CREB signaling, but enhanced PKAcβ-CREB signaling. The role of O-GlcNAcylation in PKA-CREB signaling was desensitized by insulin treatment. This study suggests a role of O-GlcNAcylation in PKA-CREB signaling by affecting phosphorylation of CREB in a PKAc isoform-specific manner. Copyright © 2018 Elsevier Inc. All rights reserved.

Exogenous administration of Substance P enhances wound healing in a novel skin-injury model.

PubMed

Delgado, Angel V; McManus, Albert T; Chambers, James P

2005-04-01

Soft tissue injury accounts for approximately 44% of all wounds in both the military and civilian populations. Following injury to soft tissue, Substance P (SP) and other neuropeptides are released by cutaneous neurons and modulate the function of immunocompetent and inflammatory cells, as well as epithelial and endothelial cells. The interaction between these components of the nervous system and multiple target cells affecting cutaneous repair is of increasing interest. In this report, we describe the effects of SP on wound repair in a novel, laser-induced, skin-wound model. Gross and histologic examination of laser-induced injury revealed that exogenously administered SP affects wound healing via neurite outgrowth, in addition to adhesion molecule and neurokinin-1 receptor involvement in vivo. All SP effects were decreased by pretreatment with Spantide II, an SP antagonist. The elucidation of SP-mediating mechanisms is crucial to firmly establishing the involvement and interaction of the peripheral nervous system and the immune system in cutaneous repair. Findings presented here suggest that SP participates in the complex network of mediators involved in cutaneous inflammation and wound healing.

Microbial characterization and hydrocarbon biodegradation potential of natural bilge waste microflora.

PubMed

Olivera, N L; Commendatore, M G; Delgado, O; Esteves, J L

2003-09-01

Shipping operations produce oily wastes that must be managed properly to avoid environmental pollution. The aim of this study was to characterize microorganisms occurring in ship bilge wastes placed in open lagoons and, particularly, to assess their potential to degrade polycyclic aromatic hydrocarbons (PAHs). A first-order kinetic was suitable for describing hydrocarbon biodegradation after 17 days of treatment. The calculated rate constants were 0.0668 and 0.0513 day(-1) with a corresponding half-life of 10.3 and 13.5 days for the aliphatic and aromatic hydrocarbon fractions, respectively. At day 17, PAH removal percentages were: acenaphtylene 100, fluorene 95.2, phenanthrene 93.6, anthracene 70.3, and pyrene 71.5. Methyl phenanthrene removals were lower than that of their parent compound (3-methyl phenanthrene 83.6, 2-methyl phenanthrene 80.8, 1-methyl phenanthrene 77.3, 9-methyl phenanthrene 75.1, and 2,7-dimethyl phenanthrene 76.6). Neither pure cultures nor the microbial community from these wastes showed extracellular biosurfactant production suggesting that the addition of an exogenously produced biosurfactant may be important in enhancing hydrocarbon bioavailability and biodegradation. DNA analysis of bilge waste samples revealed a ubiquitous distribution of the nahAc genotype in the dump pools. Although almost all of the isolates grew on naphthalene as sole carbon source, only some of them yielded nahAc amplification under the experimental conditions used. The variety of PAHs in bilge wastes could support bacteria with multiple degradation pathways and a diversity of catabolic genes divergent from the classical nah-like type.

The Physcomitrella patens exocyst subunit EXO70.3d has distinct roles in growth and development, and is essential for completion of the moss life cycle.

PubMed

Rawat, Anamika; Brejšková, Lucie; Hála, Michal; Cvrčková, Fatima; Žárský, Viktor

2017-10-01

The exocyst, an evolutionarily conserved secretory vesicle-tethering complex, spatially controls exocytosis and membrane turnover in fungi, metazoans and plants. The exocyst subunit EXO70 exists in multiple paralogs in land plants, forming three conserved clades with assumed distinct roles. Here we report functional analysis of the first moss exocyst subunit to be studied, Physcomitrella patens PpEXO70.3d (Pp1s97_91V6), from the, as yet, poorly characterized EXO70.3 clade. Following phylogenetic analysis to confirm the presence of three ancestral land plant EXO70 clades outside angiosperms, we prepared and phenotypically characterized loss-of-function Ppexo70.3d mutants and localized PpEXO70.3d in vivo using green fluorescent protein-tagged protein expression. Disruption of PpEXO70.3d caused pleiotropic cell elongation and differentiation defects in protonemata, altered response towards exogenous auxin, increased endogenous IAA concentrations, along with defects in bud and gametophore development. During mid-archegonia development, an abnormal egg cell is formed and subsequently collapses, resulting in mutant sterility. Mutants exhibited altered cell wall and cuticle deposition, as well as compromised cytokinesis, consistent with the protein localization to the cell plate. Despite some functional redundancy allowing survival of moss lacking PpEXO70.3d, this subunit has an essential role in the moss life cycle, indicating sub-functionalization within the moss EXO70 family. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Multiple-Input Subject-Specific Modeling of Plasma Glucose Concentration for Feedforward Control.

PubMed

Kotz, Kaylee; Cinar, Ali; Mei, Yong; Roggendorf, Amy; Littlejohn, Elizabeth; Quinn, Laurie; Rollins, Derrick K

2014-11-26

The ability to accurately develop subject-specific, input causation models, for blood glucose concentration (BGC) for large input sets can have a significant impact on tightening control for insulin dependent diabetes. More specifically, for Type 1 diabetics (T1Ds), it can lead to an effective artificial pancreas (i.e., an automatic control system that delivers exogenous insulin) under extreme changes in critical disturbances. These disturbances include food consumption, activity variations, and physiological stress changes. Thus, this paper presents a free-living, outpatient, multiple-input, modeling method for BGC with strong causation attributes that is stable and guards against overfitting to provide an effective modeling approach for feedforward control (FFC). This approach is a Wiener block-oriented methodology, which has unique attributes for meeting critical requirements for effective, long-term, FFC.

Transcriptome alteration in Phytophthora infestans in response to phenazine-1-carboxylic acid production by Pseudomonas fluorescens strain LBUM223.

PubMed

Roquigny, Roxane; Novinscak, Amy; Arseneault, Tanya; Joly, David L; Filion, Martin

2018-06-19

Phytophthora infestans is responsible for late blight, one of the most important potato diseases. Phenazine-1-carboxylic acid (PCA)-producing Pseudomonas fluorescens strain LBUM223 isolated in our laboratory shows biocontrol potential against various plant pathogens. To characterize the effect of LBUM223 on the transcriptome of P. infestans, we conducted an in vitro time-course study. Confrontational assay was performed using P. infestans inoculated alone (control) or with LBUM223, its phzC- isogenic mutant (not producing PCA), or exogenically applied PCA. Destructive sampling was performed at 6, 9 and 12 days and the transcriptome of P. infestans was analysed using RNA-Seq. The expression of a subset of differentially expressed genes was validated by RT-qPCR. Both LBUM223 and exogenically applied PCA significantly repressed P. infestans' growth at all times. Compared to the control treatment, transcriptomic analyses showed that the percentages of all P. infestans' genes significantly altered by LBUM223 and exogenically applied PCA increased as time progressed, from 50 to 61% and from to 32 to 46%, respectively. When applying an absolute cut-off value of 3 fold change or more for all three harvesting times, 207 genes were found significantly differentially expressed by PCA, either produced by LBUM223 or exogenically applied. Gene ontology analysis revealed that both treatments altered the expression of key functional genes involved in major functions like phosphorylation mechanisms, transmembrane transport and oxidoreduction activities. Interestingly, even though no host plant tissue was present in the in vitro system, PCA also led to the overexpression of several genes encoding effectors. The mutant only slightly repressed P. infestans' growth and barely altered its transcriptome. Our study suggests that PCA is involved in P. infestans' growth repression and led to important transcriptomic changes by both up- and down-regulating gene expression in P. infestans over time. Different metabolic functions were altered and many effectors were found to be upregulated, suggesting their implication in biocontrol.

Biochemical characterization of a recombinant Lactobacillus acidophilus strain expressing exogenous FomA protein.

PubMed

Ma, Li; Li, Fei; Zhang, Xiangyu; Feng, Xiping

2018-04-30

In previous research, to combine the immunogenicity of Fusobacterium nucleatum (F. nucleatum) and the probiotic properties of Lactobacillus acidophilus (L. acidophilus), we constructed a FomA-expressing L. acidophilus strain and assessed its immunogenicity. Our findings indicated that oral administration of the recombinant L. acidophilus strain reduced the risk of periodontal infection by Porphyromonas gingivalis (P. gingivalis) and F. nucleatum. However, because the exogenous FomA is an heterologous protein for the original bacterium, in this study, we assessed whether the biochemical characteristics of the recombinant L. acidophilus strain change due to the expression of the exogenous FomA protein. To test the biochemical characteristics of a recombinant L. acidophilus strain expressing exogenous FomA and assess its antibiotic sensitivity. We assessed the colony morphology, growth, acid production, and carbohydrate fermentation abilities of the recombinant L. acidophilus strain. In addition, we tested the adhesive ability and antimicrobial activity of the recombinant and assessed its antibiotic sensitivity through a drug susceptibility test. The experimental results showed that the colony and microscopic morphology of the recombinant L. acidophilus strain was consistent with the original strain, and the recombinant strain grew well when cultured under aerobic or anaerobic conditions, exhibiting a growth rate that was identical to that of the standard strain. Similarly, the supernatants of the recombinant L. acidophilus can inhibit the growth of E. coli and P. gingivalis at different concentrations, and the recombinant strain displayed essentially the same drug sensitivity profile as the original L. acidophilus. However, to our surprise, the recombinant strains exhibited a greater adhesion ability than the reference strain. Our study demonstrated that, in addition to an increased adhesion ability, the recombinant L. acidophilus strain maintained the basic characteristics of the standard strain ATCC 4356, including antibiotic sensitivity. Thus, the recombinant strains have great potential to be utilized as a safe and effective periodontitis vaccine in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Frailty in elderly: a brief review.

PubMed

Tabue-Teguo, Maturin; Simo, Nadine; Gonzalez-Colaço Harmand, Magali; Cesari, Matteo; Avila-Funes, Jose-Alberto; Féart, Catherine; Amiéva, Hélène; Dartigues, Jean-François

2017-06-01

The identification of frail older persons is a public health priority. Frailty is defined as an extreme vulnerability of the organism to endogenous and exogenous stressors, a syndrome that exposes the individual at higher risk of negative health-related outcomes as well as a transition phase between successful aging and disability. The theoretical concept of frailty is largely agreed, its practical translation still presents some limitations due to the existence of multiple tools and operational definition. In this brief review, we would like to clarify the frailty concept regarding scientific literature.

Checkpoint Kinase-Dependent Regulation of DNA Repair and Genome Instability in Breast Cancer

DTIC Science & Technology

2007-06-01

its misregulation (16). Exposure to exogenous DNA damaging agents induces the destruction of Cdt1 specifically by DDB1-Cul4A (7) (9). Our data...sodium citrate ) for 15 min at 37°C, fixed by multiple washes with Carnoy fixative (3:1 methanol-acetic acid), and dropped onto slides. Slides were...damaging agents induces the destruction of Cdt1 specifically by DDB1- Cul4A (24, 26). Our data indicate that DDB1 also has an important role in the

Neural correlates of endogenous attention, exogenous attention and inhibition of return in touch.

PubMed

Jones, Alexander; Forster, Bettina

2014-07-01

Selective attention helps process the myriad of information constantly touching our body. Both endogenous and exogenous mechanisms are relied upon to effectively process this information; however, it is unclear how they relate in the sense of touch. In three tasks we contrasted endogenous and exogenous event-related potential (ERP) and behavioural effects. Unilateral tactile cues were followed by a tactile target at the same or opposite hand. Clear behavioural effects showed facilitation of expected targets both when the cue predicted targets at the same (endogenous predictive task) and opposite hand (endogenous counter-predictive task), and these effects also correlated with ERP effects of endogenous attention. In an exogenous task, where the cue was non-informative, inhibition of return (IOR) was observed. The electrophysiological results demonstrated early effects of exogenous attention followed by later endogenous attention modulations. These effects were independent in both the endogenous predictive and exogenous tasks. However, voluntarily directing attention away from a cued body part influenced the early exogenous marker (N80). This suggests that the two mechanisms are interdependent, at least when the task requires more demanding shifts of attention. The early marker of exogenous tactile attention, the N80, was not directly related to IOR, which may suggest that exogenous attention and IOR are not necessarily two sides of the same coin. This study adds valuable new insight into how we process and select information presented to our body, showing both independent and interdependent effects of endogenous and exogenous attention in touch. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Strategies to improve fiber utilization in swine

PubMed Central

2013-01-01

Application of feed processing methods and use of exogenous feed additives in an effort to improve nutrient digestibility of plant-based feed ingredients for swine has been studied for decades. The following review will discuss several of these topics, including: fiber characterization, impact of dietary fiber on gastrointestinal physiology, energy, and nutrient digestibility, mechanical processing of feed on fiber and energy digestibility, and the use of exogenous enzymes in diets fed to growing pigs. Taken together, the diversity and concentration of chemical characteristics that exists among plant-based feed ingredients, as well as interactions among constituents within feed ingredients and diets, suggests that improvements in nutrient digestibility and pig performance from mechanical processing or adding exogenous enzymes to diets fed to swine depends on a better understanding of these characteristics, but also relating enzyme activity to targeted substrates. It may be that an enzyme must not only match a target substrate(s), but there may also need to be a ′cocktail′ of enzymes to effectively breakdown the complex matrixes of fibrous carbohydrates, such that the negative impact of these compounds on nutrient digestibility or voluntary feed intake are alleviated. With the inverse relationship between fiber content and energy digestibility being well described for several feed ingredients, it is only logical that development of processing techniques or enzymes that degrade fiber, and thereby improve energy digestibility or voluntary feed intake, will be both metabolically and economically beneficial to pork production. PMID:23497595

Modification of tooth development by heat shock protein 60

PubMed Central

Papp, Tamas; Polyak, Angela; Papp, Krisztina; Meszar, Zoltan; Zakany, Roza; Meszar-Katona, Eva; Tünde, Palne Terdik; Ham, Chang Hwa; Felszeghy, Szabolcs

2016-01-01

Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2-deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes. PMID:27025262

Bis(μ-oxo) dicopper(III) species of the simplest peralkylated diamine: enhanced reactivity toward exogenous substrates.

PubMed

Kang, Peng; Bobyr, Elena; Dustman, John; Hodgson, Keith O; Hedman, Britt; Solomon, Edward I; Stack, T Daniel P

2010-12-06

N,N,N',N'-tetramethylethylenediamine (TMED), the simplest and most extensively used peralkylated diamine ligand, is conspicuously absent from those known to form a bis(μ-oxo)dicopper(III) (O) species, [(TMED)(2)Cu(III)(2)(μ(2)-O)(2)](2+), upon oxygenation of its Cu(I) complex. Presented here is the characterization of this O species and its reactivity toward exogenous substrates. Its formation is complicated both by the instability of the [(TMED)Cu(I)](1+) precursor and by competitive formation of a presumed mixed-valent trinuclear [(TMED)(3)Cu(III)Cu(II)(2)(μ(3)-O)(2)](3+) (T) species. Under most reaction conditions, the T species dominates, yet, the O species can be formed preferentially (>80%) upon oxygenation of acetone solutions, if the copper concentration is low (<2 mM) and [(TMED)Cu(I)](1+) is prepared immediately before use. The experimental data of this simplest O species provide a benchmark by which to evaluate density functional theory (DFT) computational methods for geometry optimization and spectroscopic predictions. The enhanced thermal stability of [(TMED)(2)Cu(III)(2)(μ(2)-O)(2)](2+) and its limited steric demands compared to other O species allows more efficient oxidation of exogenous substrates, including benzyl alcohol to benzaldehyde (80% yield), highlighting the importance of ligand structure to not only enhance the oxidant stability but also maintain accessibility to the nascent metal/O(2) oxidant.

In vitro study of the impact of mechanical tension on the dermal fibroblast phenotype in the context of skin wound healing.

PubMed

Rolin, Gwenae L; Binda, Delphine; Tissot, Marion; Viennet, Céline; Saas, Philippe; Muret, Patrice; Humbert, Philippe

2014-11-07

Skin wound healing is finely regulated by both matrix synthesis and degradation which are governed by dermal fibroblast activity. Actually, fibroblasts synthesize numerous extracellular matrix proteins (i.e., collagens), remodeling enzymes and their inhibitors. Moreover, they differentiate into myofibroblasts and are able to develop endogenous forces at the wound site. Such forces are crucial during skin wound healing and have been widely investigated. However, few studies have focused on the effect of exogenous mechanical tension on the dermal fibroblast phenotype, which is the objective of the present paper. To this end, an exogenous, defined, cyclic and uniaxial mechanical strain was applied to fibroblasts cultured as scratch-wounded monolayers. Results showed that fibroblasts' response was characterized by both an increase in procollagen type-I and TIMP-1 synthesis, and a decrease in MMP-1 synthesis. The monitoring of scratch-wounded monolayers did not show any decrease in kinetics of the filling up when mechanical tension was applied. Additional results obtained with proliferating fibroblasts and confluent monolayer indicated that mechanical tension-induced response of fibroblasts depends on their culture conditions. In conclusion, mechanical tension leads to the differentiation of dermal fibroblasts and may increase their wound-healing capacities. So, the exogenous uniaxial and cyclic mechanical tension reported in the present study may be considered in order to improve skin wound healing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exogenous ghrelin regulates proliferation and apoptosis in the hypotrophic gut mucosa of the rat.

PubMed

de Segura, Ignacio A Gómez; Vallejo-Cremades, María Teresa; Lomas, Jesús; Sánchez, Miriam F; Caballero, María Isabel; Largo, Carlota; De Miguel, Enrique

2010-04-01

Ghrelin is the natural endogenous ligand for growth hormone secretagogue receptors. This peptide regulates energy homeostasis and expenditure and is a potential link between gut absorptive function and growth. We hypothesized that ghrelin may induce a proliferative and antiapoptotic action promoting the recovery of the hypotrophic gut mucosa. Therefore, the aim of the study was to determine the action of exogenous ghrelin following gut mucosal hypotrophia in rats fed an elemental diet. An elemental diet provides readily absorbable simple nutrients and is usually given to patients with absorptive dysfunction. Male Wistar rats (n = 48) were fed the elemental diet for one week to induce mucosal hypotrophy and then treated for another week with systemic ghrelin and pair-fed with either a normoproteic or hyperproteic isocaloric liquid diet. Another group received a standard diet instead of the elemental diet and served as control (normotrophy). The elemental diet induced intestinal hypotrophia characterized by decreased proliferation in the ileum and increased apoptosis in jejunum and ileum. Ghrelin administration restored normal levels of proliferation in the ileum and apoptosis in the jejunum, with partial apoptosis restoration in the ileum. Ghrelin levels in plasma and fundus were increased in all groups, although the highest levels were found in rats treated with exogenous ghrelin. Ghrelin administration has a positive effect in the hypotrophic gut, regulating both proliferation and apoptosis towards a physiological balance counteracting the negative changes induced by an elemental diet in the intestines.

Effect of exogenous reductant on growth and iron mobilization from ferrihydrite by the Pseudomonas mendocina ymp strain.

PubMed

Dhungana, Suraj; Anthony, Charles R; Hersman, Larry E

2007-05-01

Growth of the Pseudomonas mendocina ymp strain on insoluble ferrihydrite is enhanced by exogenous reductants with concurrent increase in soluble iron concentrations. This shows that exogenous reductants play a substantial role in the overall microbial iron bioavailability. The exogenous reductants may work together with the siderophores, Fe-scavenging agents, to facilitate ferrihydrite dissolution.

Reward can modulate attentional capture, independent of top-down set.

PubMed

Munneke, Jaap; Hoppenbrouwers, Sylco S; Theeuwes, Jan

2015-11-01

The traditional distinction between exogenous and endogenous attentional control has recently been enriched with an additional mode of control, termed "selection history." Recent findings have indicated, for instance, that previously rewarded or punished stimuli capture more attention than their physical attributes would predict. As such, the value that is associated with certain stimuli modulates attentional capture. This particular influence has also been shown for endogenous attention. Although recent leads have emerged, elucidating the influences of reward on exogenous and endogenous attention, it remains unclear to what extent exogenous attention is modulated by reward when endogenous attention is already deployed. We used a Posner cueing task in which exogenous and endogenous cues were presented to guide attention. Crucially, the exogenous cue also indicated the reward value. That is, the color of the exogenous cue indicated how much reward could be obtained on a given trial. The results showed main effects of endogenous and exogenous attention (i.e., speeded reaction times when either cue was valid, as compared to when it was invalid). Crucially, an interaction between exogenous cue validity and reward level was observed, indicating that reward-based associative-learning processes rapidly influence attentional capture, even when endogenous attention has been actively deployed.

Perspectives of breast cancer etiology: synergistic interaction between smoking and exogenous hormone use

PubMed Central

Zhu, Hong-Hong; Hu, Cao-Hui; Strickland, Paul

2011-01-01

To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast Carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing of breast cells; (3) role of exogenous hormones in breast Carcinogenesis; (4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast Carcinogenesis; and (5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer. PMID:21718589

Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors.

PubMed

Roy, Bibhas; Venkatachalapathy, Saradha; Ratna, Prasuna; Wang, Yejun; Jokhun, Doorgesh Sharma; Nagarajan, Mallika; Shivashankar, G V

2018-05-22

Cells in tissues undergo transdifferentiation programs when stimulated by specific mechanical and biochemical signals. While seminal studies have demonstrated that exogenous biochemical factors can reprogram somatic cells into pluripotent stem cells, the critical roles played by mechanical signals in such reprogramming process have not been well documented. In this paper, we show that laterally confined growth of fibroblasts on micropatterned substrates induces nuclear reprogramming with high efficiency in the absence of any exogenous reprogramming factors. We provide compelling evidence on the induction of stem cell-like properties using alkaline phosphatase assays and expression of pluripotent markers. Early onset of reprogramming was accompanied with enhanced nuclear dynamics and changes in chromosome intermingling degrees, potentially facilitating rewiring of the genome. Time-lapse analysis of promoter occupancy by immunoprecipitation of H3K9Ac chromatin fragments revealed that epithelial, proliferative, and reprogramming gene promoters were progressively acetylated, while mesenchymal promoters were deacetylated by 10 days. Consistently, RNA sequencing analysis showed a systematic progression from mesenchymal to stem cell transcriptome, highlighting pathways involving mechanisms underlying nuclear reprogramming. We then demonstrated that these mechanically reprogrammed cells could be maintained as stem cells and can be redifferentiated into multiple lineages with high efficiency. Importantly, we also demonstrate the induction of cancer stemness properties in MCF7 cells grown in such laterally confined conditions. Collectively, our results highlight an important generic property of somatic cells that, when grown in laterally confined conditions, acquire stemness. Such mechanical reprogramming of somatic cells demonstrated here has important implications in tissue regeneration and disease models. Copyright © 2018 the Author(s). Published by PNAS.

The cysteine2/histidine2-type transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 6-activated C-REPEAT-BINDING FACTOR pathway is essential for melatonin-mediated freezing stress resistance in Arabidopsis.

PubMed

Shi, Haitao; Chan, Zhulong

2014-09-01

Melatonin (N-acetyl-5-methoxytryptamine) is not only a widely known animal hormone, but also an important regulator in plant development and multiple abiotic stress responses. Recently, it has been revealed that melatonin alleviated cold stress through mediating several cold-related genes, including C-REPEAT-BINDING FACTORs (CBFs)/Drought Response Element Binding factors (DREBs), COR15a, and three transcription factors (CAMTA1, ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10), and ZAT12). In this study, we quantified the endogenous melatonin level in Arabidopsis plant leaves and found the endogenous melatonin levels were significantly induced by cold stress (4 °C) treatment. In addition, we found one cysteine2/histidine2-type zinc finger transcription factor, ZAT6, was involved in melatonin-mediated freezing stress response in Arabidopsis. Interestingly, exogenous melatonin enhanced freezing stress resistance was largely alleviated in AtZAT6 knockdown plants, but was enhanced in AtZAT6 overexpressing plants. Moreover, the expression levels of AtZAT6 and AtCBFs were commonly upregulated by cold stress (4 °C) and exogenous melatonin treatments, and modulation of AtZAT6 expression significantly affected the induction AtCBFs transcripts by cold stress (4 °C) and exogenous melatonin treatments. Taken together, AtZAT6-activated CBF pathway might be essential for melatonin-mediated freezing stress response in Arabidopsis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of Defective and Persistent Sendai Virus Vector

PubMed Central

Nishimura, Ken; Sano, Masayuki; Ohtaka, Manami; Furuta, Birei; Umemura, Yoko; Nakajima, Yoshiro; Ikehara, Yuzuru; Kobayashi, Toshihiro; Segawa, Hiroaki; Takayasu, Satoko; Sato, Hideyuki; Motomura, Kaori; Uchida, Eriko; Kanayasu-Toyoda, Toshie; Asashima, Makoto; Nakauchi, Hiromitsu; Yamaguchi, Teruhide; Nakanishi, Mahito

2011-01-01

The ectopic expression of transcription factors can reprogram differentiated tissue cells into induced pluripotent stem cells. However, this is a slow and inefficient process, depending on the simultaneous delivery of multiple genes encoding essential reprogramming factors and on their sustained expression in target cells. Moreover, once cell reprogramming is accomplished, these exogenous reprogramming factors should be replaced with their endogenous counterparts for establishing autoregulated pluripotency. Complete and designed removal of the exogenous genes from the reprogrammed cells would be an ideal option for satisfying this latter requisite as well as for minimizing the risk of malignant cell transformation. However, no single gene delivery/expression system has ever been equipped with these contradictory characteristics. Here we report the development of a novel replication-defective and persistent Sendai virus (SeVdp) vector based on a noncytopathic variant virus, which fulfills all of these requirements for cell reprogramming. The SeVdp vector could accommodate up to four exogenous genes, deliver them efficiently into various mammalian cells (including primary tissue cells and human hematopoietic stem cells) and express them stably in the cytoplasm at a prefixed balance. Furthermore, interfering with viral transcription/replication using siRNA could erase the genomic RNA of SeVdp vector from the target cells quickly and thoroughly. A SeVdp vector installed with Oct4/Sox2/Klf4/c-Myc could reprogram mouse primary fibroblasts quite efficiently; ∼1% of the cells were reprogrammed to Nanog-positive induced pluripotent stem cells without chromosomal gene integration. Thus, this SeVdp vector has potential as a tool for advanced cell reprogramming and for stem cell research. PMID:21138846

An exclusive metabolic niche enables strain engraftment in the gut microbiota.

PubMed

Shepherd, Elizabeth Stanley; DeLoache, William C; Pruss, Kali M; Whitaker, Weston R; Sonnenburg, Justin L

2018-05-01

The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time 1 . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota 2,3 . Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain 4 , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.

The impact of 2-dose routine measles, mumps, rubella, and varicella vaccination in France on the epidemiology of varicella and zoster using a dynamic model with an empirical contact matrix.

PubMed

Ouwens, Mario J N M; Littlewood, Kavi J; Sauboin, Christophe; Téhard, Bertrand; Denis, François; Boëlle, Pierre-Yves; Alain, Sophie

2015-04-01

Varicella has a high incidence affecting the vast majority of the population in France and can lead to severe complications. Almost every individual infected by varicella becomes susceptible to herpes zoster later in life due to reactivation of the latent virus. Zoster is characterized by pain that can be long-lasting in some cases and has no satisfactory treatment. Routine varicella vaccination can prevent varicella. The vaccination strategy of replacing both doses of measles, mumps, and rubella (MMR) with a combined MMR and varicella (MMRV) vaccine is a means of reaching high vaccination coverage for varicella immunization. The objective of this analysis was to assess the impact of routine varicella vaccination, with MMRV in place of MMR, on the incidence of varicella and zoster diseases in France and to assess the impact of exogenous boosting of zoster incidence, age shift in varicella cases, and other possible indirect effects. A dynamic transmission population-based model was developed using epidemiological data for France to determine the force of infection, as well as an empirically derived contact matrix to reduce assumptions underlying these key drivers of dynamic models. Scenario analyses tested assumptions regarding exogenous boosting, vaccine waning, vaccination coverage, risk of complications, and contact matrices. The model provides a good estimate of the incidence before varicella vaccination implementation in France. When routine varicella vaccination is introduced with French current coverage levels, varicella incidence is predicted to decrease by 57%, and related complications are expected to decrease by 76% over time. After vaccination, it is observed that exogenous boosting is the main driver of change in zoster incidence. When exogenous boosting is assumed, there is a temporary increase in zoster incidence before it gradually decreases, whereas without exogenous boosting, varicella vaccination leads to a gradual decrease in zoster incidence. Changing vaccine efficacy waning levels and coverage assumptions are still predicted to result in overall benefits with varicella vaccination. In conclusion, the model predicted that MMRV vaccination can significantly reduce varicella incidence. With suboptimal coverage, a limited age shift of varicella cases is predicted to occur post-vaccination with MMRV. However, it does not result in an increase in the number of complications. GSK study identifier: HO-12-6924. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Photobiological hydrogen production with switchable photosystem-II designer algae

DOEpatents

Lee, James Weifu

2014-02-18

A process for enhanced photobiological H.sub.2 production using transgenic alga. The process includes inducing exogenous genes in a transgenic alga by manipulating selected environmental factors. In one embodiment inducing production of an exogenous gene uncouples H.sub.2 production from existing mechanisms that would downregulate H.sub.2 production in the absence of the exogenous gene. In other embodiments inducing an exogenous gene triggers a cascade of metabolic changes that increase H.sub.2 production. In some embodiments the transgenic alga are rendered non-regenerative by inducing exogenous transgenes for proton channel polypeptides that are targeted to specific algal membranes.

QEEN Workshop: "Quantifying Exposure to Engineered Nano ...

EPA Pesticide Factsheets

The measurement and characterization of nanomaterials in biological tissues is complicated by a number of factors including: the sensitivity of the assay to small sized particles or low concentrations of materials; the ability to distinguish different forms and transformations of the materials related to the biological matrix; distinguishing exogenous nanomaterials, which may be composed of biologically common elements such as carbon,from normal biological tissues; differentiating particle from ionic phases for materials that dissolve; localization of sparsely distributed materials in a complex substrate (the

A high throughput spectral image microscopy system

NASA Astrophysics Data System (ADS)

Gesley, M.; Puri, R.

2018-01-01

A high throughput spectral image microscopy system is configured for rapid detection of rare cells in large populations. To overcome flow cytometry rates and use of fluorophore tags, a system architecture integrates sample mechanical handling, signal processors, and optics in a non-confocal version of light absorption and scattering spectroscopic microscopy. Spectral images with native contrast do not require the use of exogeneous stain to render cells with submicron resolution. Structure may be characterized without restriction to cell clusters of differentiation.

Association of N 2-fixing Cyanobacteria and Plants: Towards Novel Symbioses of Agricultural Importance. Final report, 1 April 1996 to 31 May 1997

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

Gantar, Miroslav

1999-03-01

The goal of this project is to characterize an association that takes place between the roots of wheat and the nitrogen-fixing cyanobacterium Nostoc 2S9. By understanding how the association takes place and the extent to which it permits the growth of the plant without exogenous nitrogenous fertilizer, it may prove possible to increase the benefits of the association and to extend them to other plants of agrinomic importance.

Central nervous system remyelination in culture--a tool for multiple sclerosis research.

PubMed

Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

2011-07-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

Central nervous system remyelination in culture — A tool for multiple sclerosis research

PubMed Central

Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

2011-01-01

Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection.

PubMed

Saxena, Kapil; Simon, Lukas M; Zeng, Xi-Lei; Blutt, Sarah E; Crawford, Sue E; Sastri, Narayan P; Karandikar, Umesh C; Ajami, Nadim J; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E; Shaw, Chad A; Estes, Mary K

2017-01-24

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine.

An infrared optical pacing system for high-throughput screening of cardiac electrophysiology in human cardiomyocytes (Conference Presentation)

NASA Astrophysics Data System (ADS)

McPheeters, Matt T.; Wang, Yves T.; Laurita, Kenneth R.; Jenkins, Michael W.

2017-02-01

Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-HCM) have the potential to provide individualized therapies for patients and to test drug candidates for cardiac toxicity. In order for hiPS-CM to be useful for such applications, there is a need for high-throughput technology to rapidly assess cardiac electrophysiology parameters. Here, we designed and tested a fully contactless optical mapping (OM) and optical pacing (OP) system capable of imaging and point stimulation of hiPS-CM in small wells. OM allowed us to characterize cardiac electrophysiological parameters (conduction velocity, action potential duration, etc.) using voltage-sensitive dyes with high temporal and spatial resolution over the entire well. To improve OM signal-to-noise ratio, we tested a new voltage-sensitive dye (Fluovolt) for accuracy and phototoxicity. Stimulation is essential because most electrophysiological parameters are rate dependent; however, traditional methods utilizing electrical stimulation is difficult in small wells. To overcome this limitation, we utilized OP (λ = 1464 nm) to precisely control heart rate with spatial precision without the addition of exogenous agents. We optimized OP parameters (e.g., well size, pulse width, spot size) to achieve robust pacing and minimize the threshold radiant exposure. Finally, we tested system sensitivity using Flecainide, a drug with well described action on multiple electrophysiological properties.

A MISO-ARX-Based Method for Single-Trial Evoked Potential Extraction.

PubMed

Yu, Nannan; Wu, Lingling; Zou, Dexuan; Chen, Ying; Lu, Hanbing

2017-01-01

In this paper, we propose a novel method for solving the single-trial evoked potential (EP) estimation problem. In this method, the single-trial EP is considered as a complex containing many components, which may originate from different functional brain sites; these components can be distinguished according to their respective latencies and amplitudes and are extracted simultaneously by multiple-input single-output autoregressive modeling with exogenous input (MISO-ARX). The extraction process is performed in three stages: first, we use a reference EP as a template and decompose it into a set of components, which serve as subtemplates for the remaining steps. Then, a dictionary is constructed with these subtemplates, and EPs are preliminarily extracted by sparse coding in order to roughly estimate the latency of each component. Finally, the single-trial measurement is parametrically modeled by MISO-ARX while characterizing spontaneous electroencephalographic activity as an autoregression model driven by white noise and with each component of the EP modeled by autoregressive-moving-average filtering of the subtemplates. Once optimized, all components of the EP can be extracted. Compared with ARX, our method has greater tracking capabilities of specific components of the EP complex as each component is modeled individually in MISO-ARX. We provide exhaustive experimental results to show the effectiveness and feasibility of our method.

Parameterizing the Variability and Uncertainty of Wind and Solar in CEMs

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

Frew, Bethany

We present current and improved methods for estimating the capacity value and curtailment impacts from variable generation (VG) in capacity expansion models (CEMs). The ideal calculation of these variability metrics is through an explicit co-optimized investment-dispatch model using multiple years of VG and load data. Because of data and computational limitations, existing CEMs typically approximate these metrics using a subset of all hours from a single year and/or using statistical methods, which often do not capture the tail-event impacts or the broader set of interactions between VG, storage, and conventional generators. In our proposed new methods, we use hourly generationmore » and load values across all hours of the year to characterize the (1) contribution of VG to system capacity during high load hours, (2) the curtailment level of VG, and (3) the reduction in VG curtailment due to storage and shutdown of select thermal generators. Using CEM model outputs from a preceding model solve period, we apply these methods to exogenously calculate capacity value and curtailment metrics for the subsequent model solve period. Preliminary results suggest that these hourly methods offer improved capacity value and curtailment representations of VG in the CEM from existing approximation methods without additional computational burdens.« less

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

PubMed Central

Saxena, Kapil; Simon, Lukas M.; Zeng, Xi-Lei; Blutt, Sarah E.; Crawford, Sue E.; Sastri, Narayan P.; Karandikar, Umesh C.; Ajami, Nadim J.; Zachos, Nicholas C.; Kovbasnjuk, Olga; Donowitz, Mark; Conner, Margaret E.; Shaw, Chad A.; Estes, Mary K.

2017-01-01

The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine. PMID:28069942

A reconnaissance analysis of groundwater quality in the Eagle Ford shale region reveals two distinct bromide/chloride populations.

PubMed

Hildenbrand, Zacariah L; Carlton, Doug D; Meik, Jesse M; Taylor, Josh T; Fontenot, Brian E; Walton, Jayme L; Henderson, Drew; Thacker, Jonathan B; Korlie, Stephanie; Whyte, Colin J; Hudak, Paul F; Schug, Kevin A

2017-01-01

The extraction of oil and natural gas from unconventional shale formations has prompted a series of investigations to examine the quality of the groundwater in the overlying aquifers. Here we present a reconnaissance analysis of groundwater quality in the Eagle Ford region of southern Texas. These data reveal two distinct sample populations that are differentiable by bromide/chloride ratios. Elevated levels of fluoride, nitrate, sulfate, various metal ions, and the detection of exotic volatile organic compounds highlight a high bromide group of samples, which is geographically clustered, while encompassing multiple hydrogeological strata. Samples with bromide/chloride ratios representative of connate water displayed elevated levels of total organic carbon, while revealing the detection of alcohols and chlorinated compounds. These findings suggest that groundwater quality in the Western Gulf Basin is, for the most part, controlled by a series of natural processes; however, there is also evidence of episodic contamination events potentially attributed to unconventional oil and gas development or other anthropogenic activities. Collectively, this characterization of natural groundwater constituents and exogenous compounds will guide targeted remediation efforts and provides insight for agricultural entities, industrial operators, and rural communities that rely on groundwater in southern Texas. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach.

PubMed

Huang, Zhi-Yong; Xie, Hong; Cao, Ying-Lan; Cai, Chao; Zhang, Zhi

2014-02-15

The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of (206)Pb, the contamination of exogenous Pb(2+) ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60-85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60-66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation. Copyright © 2014 Elsevier B.V. All rights reserved.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PubMed

Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

2017-01-01

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].

PubMed

Yuan, Lei; Fan, Wen-Juan; Yang, Xu-Guang; Rao, Shu-Mei; Song, Jin-Ling; Song, Guo-Hua

2013-10-25

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

Out with the new, in with the old: Exogenous orienting to locations with physically constant stimulation.

PubMed

Taylor, J Eric T; Hilchey, Matthew D; Pratt, Jay

2018-01-24

Dominant methods of investigating exogenous orienting presume that attention is captured most effectively at locations containing new events. This is evidenced by the ubiquitous use of transient stimuli as cues in the literature on exogenous orienting. In the present study, we showed that attention can be oriented exogenously toward a location containing a completely unchanging stimulus by modifying Posner's landmark exogenous spatial-cueing paradigm. Observers searched a six-element array of placeholder stimuli for an onset target. The target was preceded by a decrement in luminance to five of the six placeholders, such that one location remained physically constant. This "nonset" stimulus (so named to distinguish it from a traditional onsetting transient) acted as an exogenous cue, eliciting patterns of facilitation and inhibition at the nonset location and demonstrating that exogenous orienting is not always evident at the location of a visual transient. This method eliminates the decades-long confounding of orienting to a location with the processing of new events at that location, permitting alternative considerations of the nature of attentional selection.

A novel pathway to detect and cope with exogenous dsDNA.

PubMed

Kobayashi, Shouhei; Haraguchi, Tokuko

2015-01-01

How a living cell responds to exogenous materials is one of the fundamental questions in the life sciences. In particular, understanding the mechanisms by which a cell recognizes exogenous double-stranded DNA (dsDNA) is important for immunology research because it will facilitate the control of pathogen infections that entail the presence of exogenous dsDNA in the cytoplasm of host cells. Several cytosolic dsDNA sensor proteins that trigger innate immune responses have been identified and the downstream signaling pathways have been investigated. However, the events that occur at the site of exogenous dsDNA when it is exposed to the cytosol of the host cell remain unknown. Using dsDNA-coated polystyrene beads incorporated into living cells, we recently found that barrier-to-autointegration factor (BAF) binds to the exogenous dsDNA immediately after its appearance in the cytosol and plays a role in DNA avoidance of autophagy. Our findings reveal a novel pathway in which BAF plays a key role in the detection of and response to exogenous dsDNA.

[Fibrous tissue(s): a key for lesion characterization in digestive diseases].

PubMed

Régent, D; Laurent, V; Antunes, L; Debelle, L; Cannard, L; Leclerc, Jc; Beot, S

2002-02-01

Fibrosis is one of the hallmarks of inflammatory and repair processes in pathology. Various exogenous and endogenous stimuli, including tumor development, can induce inflammatory reactions. During the post-equilibrium phase after IV injection of non specific contrast media, CT and/or MR allow the study of these inflammatory answers to tumoral or infectious processes. Delayed enhancement of collagenic fibrous tissue during the late post-equilibrium phase is an essential complementary data in the characterization of many liver lesions: cirrhosis, cholangiocarcinoma, focal nodular hyperplasia, fibrous metastasis. but also for the differential diagnosis of pancreatic diseases (groove pancreatitis vs ductal adenocarcinoma) or of gastro-intestinal diseases (gastric adenocarcinoma vs lymphoma, mechanical complication vs inflammatory bouts of ileal Crohn's disease).

Infrared and Raman spectroscopic features of plant cuticles: a review

PubMed Central

Heredia-Guerrero, José A.; Benítez, José J.; Domínguez, Eva; Bayer, Ilker S.; Cingolani, Roberto; Athanassiou, Athanassia; Heredia, Antonio

2014-01-01

The cuticle is one of the most important plant barriers. It is an external and continuous lipid membrane that covers the surface of epidermal cells and whose main function is to prevent the massive loss of water. The spectroscopic characterization of the plant cuticle and its components (cutin, cutan, waxes, polysaccharides and phenolics) by infrared and Raman spectroscopies has provided significant advances in the knowledge of the functional groups present in the cuticular matrix and on their structural role, interaction and macromolecular arrangement. Additionally, these spectroscopies have been used in the study of cuticle interaction with exogenous molecules, degradation, distribution of components within the cuticle matrix, changes during growth and development and characterization of fossil plants. PMID:25009549

Assessment of Health Effects of Exogenous Urea: Summary and Key Findings.

PubMed

Dickerson, Aisha S; Lee, Janice S; Keshava, Channa; Hotchkiss, Andrew; Persad, Amanda S

2018-05-01

Urea has been utilized as a reductant in diesel fuels to lower emission of nitrogen oxides, igniting interest in probable human health hazards associated with exposure to exogenous urea. Here, we summarize and update key findings on potential health effects of exogenous urea, including carcinogenicity. No definitive target organs for oral exposure were identified; however, results in animal studies suggest that the liver and kidney could be potential target organs of urea toxicity. The available human-subject literature suggests that the impact on lung function is minimal. Based on the literature on exogenous urea, we concluded that there was inadequate information to assess the carcinogenic potential of urea, or perform a quantitative assessment to derive reference values. Given the limited information on exogenous urea, additional research to address gaps for exogenous urea should include long-term cancer bioassays, two-generation reproductive toxicity studies, and mode-of-action investigations.

Influence of ensiling, exogenous protease addition, and bacterial inoculation on fermentation profile, nitrogen fractions, and ruminal in vitro starch digestibility in rehydrated and high-moisture corn.

PubMed

Ferraretto, L F; Fredin, S M; Shaver, R D

2015-10-01

Exogenous protease addition may be an option to increase proteolysis of zein proteins and thus starch digestibility in rehydrated and high-moisture corn (HMC) ensiled for short periods. In addition, microbial inoculation may accelerate fermentation and increase acid production and thus increase solubilization of zein proteins. Four experiments were performed to evaluate the effect on fermentation profile, N fractions, and ruminal in vitro starch digestibility (ivSD) of the following: (1) rehydration and ensiling of dry ground corn; (2) exogenous protease addition to rehydrated un-ensiled and ensiled corn; (3) exogenous protease addition or inoculation in rehydrated ensiled corn; and (4) exogenous protease addition or inoculation in HMC. Experiments 1, 2, and 3 were performed with 7 treatments: dry ground corn (DGC); DGC rehydrated to a targeted dry matter content of 70% (REH); REH treated with exogenous protease (REH+); REH ensiled for 30 d (ENS); ENS treated with exogenous protease (ENS+); ENS treated with a microbial inoculant containing Lactobacillus plantarum, Lactobacillus casei, Enterococcus faecium, and Pediococcus sp. (ENSI); and ENS treated with exogenous protease and microbial inoculant (ENSI+). Experiment 1 compared DGC, REH, and ENS with ivSD being greater for ENS (64.9%) than DGC and REH (51.7% on average). Experiment 2 compared REH and ENS without or with exogenous protease addition (REH+ and ENS+, respectively). Ensiling and exogenous protease addition increased ivSD, but exogenous protease addition was more effective in ENS than REH (6.4 vs. 2.6 percentage unit increase). Experiment 3 compared the effects of exogenous protease addition and inoculation in ENS corn (ENS, ENS+, ENSI, and ENSI+). The addition of protease, but not inoculant, increased ivSD. Inoculation reduced pH and acetate, propionate, and ethanol concentrations, and increased lactate and total acid concentrations. In experiment 4, 8 treatments were a combination of HMC noninoculated or inoculated with 1 of 3 microbial inoculants and with or without exogenous protease addition. The inoculant treatments contained (1) Lactobacillus buchneri 40788 and Pediococcus pentosaceus, (2) L. buchneri 40788, and (3) a mixture of P. pentosaceus and Propionibacterium freudenreichii. Protease, but not inoculation, increased ivSD by 7.5 percentage units (44.4 vs. 51.9%). Protease addition increased ivSD in rehydrated corn and HMC. Microbial inoculation improved fermentation profiles but did not affect ivSD. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The coupling hypothesis: why genome scans may fail to map local adaptation genes.

PubMed

Bierne, Nicolas; Welch, John; Loire, Etienne; Bonhomme, François; David, Patrice

2011-05-01

Genomic scans of multiple populations often reveal marker loci with greatly increased differentiation between populations. Often this differentiation coincides in space with contrasts in ecological factors, forming a genetic-environment association (GEA). GEAs imply a role for local adaptation, and so it is tempting to conclude that the strongly differentiated markers are themselves under ecologically based divergent selection, or are closely linked to loci under such selection. Here, we highlight an alternative and neglected explanation: intrinsic (i.e. environment-independent) pre- or post-zygotic genetic incompatibilities rather than local adaptation can be responsible for increased differentiation. Intrinsic genetic incompatibilities create endogenous barriers to gene flow, also known as tension zones, whose location can shift over time. However, tension zones have a tendency to become trapped by, and therefore to coincide with, exogenous barriers due to ecological selection. This coupling of endogenous and exogenous barriers can occur easily in spatially subdivided populations, even if the loci involved are unlinked. The result is that local adaptation explains where genetic breaks are positioned, but not necessarily their existence, which can be best explained by endogenous incompatibilities. More precisely, we show that (i) the coupling of endogenous and exogenous barriers can easily occur even when ecological selection is weak; (ii) when environmental heterogeneity is fine-grained, GEAs can emerge at incompatibility loci, but only locally, in places where habitats and gene pools are sufficiently intermingled to maintain linkage disequilibria between genetic incompatibilities, local-adaptation genes and neutral loci. Furthermore, the association between the locally adapted and intrinsically incompatible alleles (i.e. the sign of linkage disequilibrium between endogenous and exogenous loci) is arbitrary and can form in either direction. Reviewing results from the literature, we find that many predictions of our model are supported, including endogenous genetic barriers that coincide with environmental boundaries, local GEA in mosaic hybrid zones, and inverted or modified GEAs at distant locations. We argue that endogenous genetic barriers are often more likely than local adaptation to explain the majority of Fst-outlying loci observed in genome scan approaches - even when these are correlated to environmental variables. © 2011 Blackwell Publishing Ltd.

High-level exogenous glutamic acid-independent production of poly-(γ-glutamic acid) with organic acid addition in a new isolated Bacillus subtilis C10.

PubMed

Zhang, Huili; Zhu, Jianzhong; Zhu, Xiangcheng; Cai, Jin; Zhang, Anyi; Hong, Yizhi; Huang, Jin; Huang, Lei; Xu, Zhinan

2012-07-01

A new exogenous glutamic acid-independent γ-PGA producing strain was isolated and characterized as Bacillus subtilis C10. The factors influencing the endogenous glutamic acid supply and the biosynthesis of γ-PGA in this strain were investigated. The results indicated that citric acid and oxalic acid showed the significant capability to support the overproduction of γ-PGA. This stimulated increase of γ-PGA biosynthesis by citric acid or oxalic acid was further proved in the 10 L fermentor. To understand the possible mechanism contributing to the improved γ-PGA production, the activities of four key intracellular enzymes were measured, and the possible carbon fluxes were proposed. The result indicated that the enhanced level of pyruvate dehydrogenase (PDH) activity caused by oxalic acid was important for glutamic acid synthesized de novo from glucose. Moreover, isocitrate dehydrogenase (ICDH) and glutamate dehydrogenase (GDH) were the positive regulators of glutamic acid biosynthesis, while 2-oxoglutarate dehydrogenase complex (ODHC) was the negative one. Copyright © 2012 Elsevier Ltd. All rights reserved.

Characterization and expression analysis of a banana gene encoding 1-aminocyclopropane-1-carboxylate oxidase.

PubMed

Huang, P L; Do, Y Y; Huang, F C; Thay, T S; Chang, T W

1997-04-01

A cDNA encoding the banana 1-aminocyclopropane-1-carboxylate (ACC) oxidase has previously been isolated from a cDNA library that was constructed by extracting poly(A)+ RNA from peels of ripening banana. This cDNA, designated as pMAO2, has 1,199 bp and contains an open reading frame of 318 amino acids. In order to identify ripening-related promoters of the banana ACC oxidase gene, pMAO2 was used as a probe to screen a banana genomic library constructed in the lambda EMBL3 vector. The banana ACC oxidase MAO2 gene has four exons and three introns, with all of the boundaries between these introns and exons sharing a consensus dinucleotide sequence of GT-AG. The expression of MAO2 gene in banana begins after the onset of ripening (stage 2) and continuous into later stages of the ripening process. The accumulation of MAO2 mRNA can be induced by 1 microliter/l exogenous ethylene, and it reached steady state level when 100 microliters/l exogenous ethylene was present.

Gliclazide-Induced Insulin Autoimmune Syndrome: A Rare Case Report and Review on Literature.

PubMed

Feng, Xiu; Yuan, Lu; Hu, Yun; Zhu, Yunqing; Yang, Fan; Jiang, Lanlan; Yan, Rengna; Luo, Yong; Zhao, Enhui; Liu, Chenxiao; Wang, Ying; Li, Qi; Cao, Xin; Li, Qian; Ma, Jianhua

2016-01-01

Insulin Autoimmune Syndrome (IAS) is a rare condition characterized by the combination of recurrent severely spontaneous hypoglycemia without evidence of exogenous insulin administration, high concentration of total serum insulin, and the presence of a high titer of insulin autoantibody (IAA). But now we describe a case with IAS caused by gliclazide and hardly occuring hypoglycemia. A 70-year-old man with type 2 diabetes presented to our department with poor glycemic control without evidence of hypoglycemia, but the levels of serum insulin and IAA were very high. He had no exogenous insulin administration history. Switching antidiabetic therapy from gliclazide to acarbose and metformin, the patient's serum insulin level and IAA decreased gradually. Accordingly, the glycemic control improved and there was no episode of hypoglycemia. Hence, clinicians should pay more attention to type 2 diabetic patients treated with gliclazide and detect their serum insulin concentration and IAA to exclude or diagnose IAS and perform the best therapeutic regimen to these patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Reproductive failure of the red shiner (Cyprinella lutrensis) after exposure to an exogenous estrogen

USGS Publications Warehouse

McGree, M.M.; Winkelman, D.L.; Vieira, N.K.M.; Vajda, A.M.

2010-01-01

Endocrine disrupting chemicals (EDCs) have been detected in surface waters worldwide and can lead to developmental and reproductive disruption in exposed fishes. In the US Great Plains, EDCs are impacting streams and rivers and may be causing adverse reproductive effects. To examine how estrogenic EDCs might affect reproductive success of plains fishes, we experimentally exposed male red shiners (Cyprinella lutrensis) to exogenous 17b-estradiol. We characterized the effects of estradiol on male gonadal histology and secondary sexual characteristics, determined whether exposure reduced reproductive success, and examined the effects of depuration. Adults were exposed to a mean concentration of 70 ng L-1 estradiol, a solvent control, or a water control for at least 83 days. Male exposure to estradiol resulted in elevated plasma vitellogenin concentrations, changes in spermatogenesis, reduced mating coloration and tubercles, altered mating behaviors, and reduced reproductive success with no viable progeny produced. Reproductive endpoints improved upon depuration (28 days). Exposure to estradiol had significant adverse effects on red shiners, indicating that wild populations may face developmental and reproductive difficulties if they are chronically exposed to estradiol.

Characterizing novel endogenous retroviruses from genetic variation inferred from short sequence reads

PubMed Central

Mourier, Tobias; Mollerup, Sarah; Vinner, Lasse; Hansen, Thomas Arn; Kjartansdóttir, Kristín Rós; Guldberg Frøslev, Tobias; Snogdal Boutrup, Torsten; Nielsen, Lars Peter; Willerslev, Eske; Hansen, Anders J.

2015-01-01

From Illumina sequencing of DNA from brain and liver tissue from the lion, Panthera leo, and tumor samples from the pike-perch, Sander lucioperca, we obtained two assembled sequence contigs with similarity to known retroviruses. Phylogenetic analyses suggest that the pike-perch retrovirus belongs to the epsilonretroviruses, and the lion retrovirus to the gammaretroviruses. To determine if these novel retroviral sequences originate from an endogenous retrovirus or from a recently integrated exogenous retrovirus, we assessed the genetic diversity of the parental sequences from which the short Illumina reads are derived. First, we showed by simulations that we can robustly infer the level of genetic diversity from short sequence reads. Second, we find that the measures of nucleotide diversity inferred from our retroviral sequences significantly exceed the level observed from Human Immunodeficiency Virus infections, prompting us to conclude that the novel retroviruses are both of endogenous origin. Through further simulations, we rule out the possibility that the observed elevated levels of nucleotide diversity are the result of co-infection with two closely related exogenous retroviruses. PMID:26493184

Treatments to Optimize the Use of Artificial Insemination and Reproductive Efficiency in Beef Cattle under Tropical Environments

PubMed Central

de Sá Filho, Ocilon Gomes; Vasconcelos, José Luiz Moraes

2011-01-01

Bos indicus cattle, the preferred genetic group in tropical climates, are characterized by having a lower reproductive efficiency than Bos taurus. The reasons for the poorer reproductive efficiency of the Bos indicus cows include longer lengths of gestation and postpartum anestrus, a short length of estrous behavior with a high incidence of estrus occurring during the dark hours, and puberty at older age and at a higher percentage of body weight relative to mature body weight. Moreover, geography, environment, economics, and social traditions are factors contributing for a lower use of reproductive biotechnologies in tropical environments. Hormonal protocols have been developed to resolve some of the reproductive challenges of the Bos indicus cattle and allow artificial insemination, which is the main strategy to hasten genetic improvement in commercial beef ranches. Most of these treatments use exogenous sources of progesterone associated with strategies to improve the final maturation of the dominant follicle, such as temporary weaning and exogenous gonadotropins. These treatments have caused large impacts on reproductive performance of beef cattle reared under tropical areas. PMID:21076547

[A pathogenesis study of tic disorder in children based on pathogen incubation theory].

PubMed

Zhou, Ya-bing; Wu, Min

2007-11-01

Pathogen incubation theory includes "no manifestation after infection" and "manifestation after incubation". Clinical data showed that the incidence and recurrence of tic disorders in children had a strong relevance to six exogenous factors. The pathogenesis is similar to the pathogenic mechanism based on incubation of pathogen theory, so we proposed a theory of "tic disorder induced by incubation of pathogen". Pathogenic wind can be classified into exterior wind and endogenous wind. Pathogenic wind is more apt to move, rise and migrate. The characteristics of pathogenic wind, especially easy mobility, determine the symptoms and signs of tic disorder, for pathogenic wind can be characterized by vibration and involuntary movement such as convulsion and tremor. If exogenous pathogenic wind moves into half-exterior and half-interior phase from the exterior, both the exterior and interior syndromes should be treated at the same time. We should regulate the function of the liver and the lung, expel pathogenic wind by dispersing the lung, and calm endogenous wind by removing obstruction in the collaterals and soothing the liver.

The relationship between event-related potentials, stress perception and personality type in patients with multiple sclerosis without cognitive impairment: A pilot study.

PubMed

Waliszewska-Prosół, Marta; Nowakowska-Kotas, Marta; Kotas, Roman; Bańkowski, Tomasz; Pokryszko-Dragan, Anna; Podemski, Ryszard

2018-06-08

The clinical course of multiple sclerosis (MS) can vary significantly among patients and is affected by exogenous and endogenous factors. Among these, stress and personality type have been gaining more attention. The aim of this study was to investigate the parameters of event-related potentials (ERPs) with regards to stress perception and personality type, as well as cognitive performance in MS patients. The study group consisted of 30 MS patients and 26 healthy controls. Auditory ERPs were performed in both groups, including an analysis of P300 and N200 response parameters. The Perceived Stress Scale (PSS) was used in the MS group to measure the perception of stress. The D-type Scale (DS14) scale was used to determine the features of Type D personality, characterized by social inhibition and negative affectivity. The score on the PSS corresponded with a moderate or high level of stress perception in 63% of MS patients, while 23% of patients presented with a Type D personality. P300 latencies were significantly longer (p = 0.001), N200 amplitudes were significantly higher (p = 0.004), and N200 latencies were longer in MS patients than in the controls. Strong positive correlations were found between N200 and P300 amplitudes, as well as between the DS14 and PSS results. Most MS patients experience moderate to severe stress. ERP abnormalities were found in MS patients who did not have overt cognitive impairment and showed correlations with stress levels and negative affectivity. Event-related potentials may be useful in assessing the influence of stress and emotions on the course of MS.

Detection and Measurement of Unhealthy, Environment-Derived Aerosol Materials in an Emergency Department.

PubMed

Choi, Bryan Y; Kobayashi, Leo; Pathania, Shivany; Miller, Courtney B; Locke, Emma R; Stearns, Branden C; Hudepohl, Nathan J; Patefield, Scott S; Suner, Selim; Williams, Kenneth A; Machan, Jason T; Jay, Gregory D

2015-01-01

To measure unhealthy aerosol materials in an Emergency Department (ED) and identify their sources for mitigation efforts. Based on pilot findings of elevated ED particulate matter (PM) levels, investigators hypothesized that unhealthy aerosol materials derive from exogenous (vehicular) sources at ambulance receiving entrances. The Aerosol Environmental Toxicity in Healthcare-related Exposure and Risk program was conducted as an observational study. Calibrated sensors monitored PM and toxic gases at Ambulance Triage Exterior (ATE), Ambulance Triage Desk (ATD), and control Public Triage Desk (PTD) on a 3/3/3-day cycle. Cassette sampling characterized PM; meteorological and ambulance traffic data were logged. Descriptive and multiple linear regression analyses assessed for interactions between aerosol material levels, location, temporal variables, ambulance activity, and meteorological factors. Sensors acquired 93,682 PM0.3, 90,250 PM2.5, and 93,768 PM5 measurements over 366 days to generate a data set representing at least 85.6% of planned measurements. PM0.3, PM2.5, and PM5 mean counts were lowest in PTD; 56%, 224%, and 223% higher in ATD; and 996%, 200%, and 63% higher in ATE, respectively (all p < .001). Qualitative analyses showed similar PM compositions in ATD and ATE. On multiple linear regression analysis, PM0.3 counts correlated primarily with location; PM2.5 and PM5 counts correlated most strongly with location and ambulance presence. PM < 2.5 and toxic gas concentrations at ATD and PTD patient care areas did not exceed hazard levels; PM0.3 counts did not have formal safety thresholds for comparison. Higher levels of PM were linked with ED ambulance areas, although their health impact is unclear. © The Author(s) 2015.

Exogenous spatial attention decreases audiovisual integration.

PubMed

Van der Stoep, N; Van der Stigchel, S; Nijboer, T C W

2015-02-01

Multisensory integration (MSI) and spatial attention are both mechanisms through which the processing of sensory information can be facilitated. Studies on the interaction between spatial attention and MSI have mainly focused on the interaction between endogenous spatial attention and MSI. Most of these studies have shown that endogenously attending a multisensory target enhances MSI. It is currently unclear, however, whether and how exogenous spatial attention and MSI interact. In the current study, we investigated the interaction between these two important bottom-up processes in two experiments. In Experiment 1 the target location was task-relevant, and in Experiment 2 the target location was task-irrelevant. Valid or invalid exogenous auditory cues were presented before the onset of unimodal auditory, unimodal visual, and audiovisual targets. We observed reliable cueing effects and multisensory response enhancement in both experiments. To examine whether audiovisual integration was influenced by exogenous spatial attention, the amount of race model violation was compared between exogenously attended and unattended targets. In both Experiment 1 and Experiment 2, a decrease in MSI was observed when audiovisual targets were exogenously attended, compared to when they were not. The interaction between exogenous attention and MSI was less pronounced in Experiment 2. Therefore, our results indicate that exogenous attention diminishes MSI when spatial orienting is relevant. The results are discussed in terms of models of multisensory integration and attention.

Dry-grind processing using amylase corn and superior yeast to reduce the exogenous enzyme requirements in bioethanol production.

PubMed

Kumar, Deepak; Singh, Vijay

2016-01-01

Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Use of amylase corn and superior yeast in the dry-grind processing industry can reduce the total external enzyme usage by more than 80 %, and combining their use with in situ removal of ethanol during fermentation allows efficient high-solid fermentation.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Construction of armored RNA containing long-size chimeric RNA by increasing the number and affinity of the pac site in exogenous rna and sequence coding coat protein of the MS2 bacteriophage.

PubMed

Wei, Baojun; Wei, Yuxiang; Zhang, Kuo; Yang, Changmei; Wang, Jing; Xu, Ruihuan; Zhan, Sien; Lin, Guigao; Wang, Wei; Liu, Min; Wang, Lunan; Zhang, Rui; Li, Jinming

2008-01-01

To construct a one-plasmid expression system of the armored RNA containing long chimeric RNA by increasing the number and affinity of the pac site. The plasmid pET-MS2-pac was constructed with one C-variant pac site, and then the plasmid pM-CR-2C containing 1,891-bp chimeric sequences and two C-variant pac sites was produced. Meanwhile, three plasmids (pM-CR-C, pM-CR-2W and pM-CR-W) were obtained as parallel controls with a different number and affinity of the pac site. Finally, the armored RNA was expressed and purified. The armored RNA with 1,891 bases target RNA was expressed successfully by the one-plasmid expression system with two C-variant pac sites, while for one pac site, no matter whether the affinity was changed or not, only the 1,200 bases target RNA was packaged. It was also found that the C-variant pac site could increase the expression efficiency of the armored RNA. The armored RNA with 1,891-bp exogenous RNA in our study showed the characterization of ribonuclease resistance and stability at different time points and temperature conditions. The armored RNA with 1,891 bases exogenous RNA was constructed and the expression system can be used as a platform for preparation of the armored RNA containing long RNA sequences. Copyright 2008 S. Karger AG, Basel.

Coupling of Physiological and Proteomic Analysis to Understand the Ethylene- and Chilling-Induced Kiwifruit Ripening Syndrome

PubMed Central

Minas, Ioannis S.; Tanou, Georgia; Karagiannis, Evangelos; Belghazi, Maya; Molassiotis, Athanassios

2016-01-01

Kiwifruit [Actinidia deliciosa (A. Chev.) C.F. Liang et A.R. Ferguson, cv. “Hayward”] is classified as climacteric fruit and the initiation of endogenous ethylene production following harvest is induced by exogenous ethylene or chilling exposure. To understand the biological basis of this “dilemma,” kiwifruit ripening responses were characterized at 20°C following treatments with exogenous ethylene (100 μL L−1, 20°C, 24 h) or/and chilling temperature (0°C, 10 days). All treatments elicited kiwifruit ripening and induced softening and endogenous ethylene biosynthesis, as determined by 1-aminocyclopropane-1-carboxylic acid (ACC) content and ACC synthase (ACS) and ACC oxidase (ACO) enzyme activities after 10 days of ripening at 20°C. Comparative proteomic analysis using two-dimensional gel electrophoresis (2DE-PAGE) and nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC-MS/MS) revealed 81 kiwifruit proteins associated with ripening. Thirty-one kiwifruit proteins were identified as commonly regulated by the three treatments accompanied by dynamic changes of 10 proteins specific to exogenous ethylene, 2 to chilling treatment, and 12 to their combination. Ethylene and/or chilling-responsive proteins were mainly involved in disease/defense, energy, protein destination/storage, and cell structure/cell wall. Interactions between the identified proteins were demonstrated by bioinformatics analysis, allowing a more complete insight into biological pathways and molecular functions affected by ripening. The present approach provides a quantitative basis for understanding the ethylene- and chilling-induced kiwifruit ripening and climacteric fruit ripening in general. PMID:26913040

[Effects of exogenous AsA and GSH on the growth of Dianthus chinensis seedlings exposed to Cd].

PubMed

Ding, Ji-Jun; Liu, Shi-Liang; Pan, Yuan-Zhi; Li, Li

2014-02-01

A pot experiment was carried out under greenhouse condition to investigate the effects of different concentrations (0, 20, 40, 60, 80 and 100 mg x L(-1)) of exogenous AsA, GSH on Dianthus chinensis seedlings which were stressed by 50 mg x kg(-1) Cd in the soil. The results indicated that 50 mg x kg(-1) of Cd significantly inhibited the growth of D. chinensis seedlings. An appropriate concentration of exogenous AsA significantly improved the biomass, plant height, tiller number, GAT and APX activities, and AsA and GSH contents. However, with the increase of exogenous AsA concentration, the ameliorating effect decreased and prooxidant effect occurred. Exogenous GSH could replenish the non-enzymatic antioxidants of D. chinensis seedlings, but the changes of antioxidant enzyme activities were relatively slight. The main mechanisms of GSH to alleviate Cd toxicity might be promoting root PCs synthesis, thereby reducing the Cd concentration in the seedlings. Both 35-45 mg x L(-1) exogenous AsA and 55-65 mg x L(-1) exogenous GSH could alleviate the Cd toxicity on D. chinensis seedlings, and the former was superior to the latter.

Comparative proteomic analysis reveals the positive effect of exogenous spermidine on photosynthesis and salinity tolerance in cucumber seedlings.

PubMed

Sang, Ting; Shan, Xi; Li, Bin; Shu, Sheng; Sun, Jin; Guo, Shirong

2016-08-01

Our results based on proteomics data and physiological alterations proposed the putative mechanism of exogenous Spd enhanced salinity tolerance in cucumber seedlings. Current studies showed that exogenous spermidine (Spd) could alleviate harmful effects of salinity. It is important to increase our understanding of the beneficial physiological responses of exogenous Spd treatment, and to determine the molecular responses underlying these responses. Here, we combined a physiological analysis with iTRAQ-based comparative proteomics of cucumber (Cucumis sativus L.) leaves, treated with 0.1 mM exogenous Spd, 75 mM NaCl and/or exogenous Spd. A total of 221 differentially expressed proteins were found and involved in 30 metabolic pathways, such as photosynthesis, carbohydrate metabolism, amino acid metabolism, stress response, signal transduction and antioxidant. Based on functional classification of the differentially expressed proteins and the physiological responses, we found cucumber seedlings treated with Spd under salt stress had higher photosynthesis efficiency, upregulated tetrapyrrole synthesis, stronger ROS scavenging ability and more protein biosynthesis activity than NaCl treatment, suggesting that these pathways may promote salt tolerance under high salinity. This study provided insights into how exogenous Spd protects photosynthesis and enhances salt tolerance in cucumber seedlings.

Exogenous temporal cues enhance recognition memory in an object-based manner.

PubMed

Ohyama, Junji; Watanabe, Katsumi

2010-11-01

Exogenous attention enhances the perception of attended items in both a space-based and an object-based manner. Exogenous attention also improves recognition memory for attended items in the space-based mode. However, it has not been examined whether object-based exogenous attention enhances recognition memory. To address this issue, we examined whether a sudden visual change in a task-irrelevant stimulus (an exogenous cue) would affect participants' recognition memory for items that were serially presented around a cued time. The results showed that recognition accuracy for an item was strongly enhanced when the visual cue occurred at the same location and time as the item (Experiments 1 and 2). The memory enhancement effect occurred when the exogenous visual cue and an item belonged to the same object (Experiments 3 and 4) and even when the cue was counterpredictive of the timing of an item to be asked about (Experiment 5). The present study suggests that an exogenous temporal cue automatically enhances the recognition accuracy for an item that is presented at close temporal proximity to the cue and that recognition memory enhancement occurs in an object-based manner.

Potential role of immunoablation and hematopoietic cell transplantation in the treatment of early diabetes type 1.

PubMed

Snarski, Emilian; Milczarczyk, Alicja; Franek, Edward; Jedrzejczak, Wieslaw

2010-01-01

Immunoablation with autologous hematopoietic cell transplantation has shown some effectiveness in the treatment of autoimmune diseases as diverse as aplastic anemia, systemic lupus erythematosus, multiple sclerosis and Crohn's disease. It has been recently shown that this treatment might prevent or delay development of diabetes type 1. The majority of more than 30 patients with early diabetes type 1 who underwent immunoablation and hematopoietic cell transplantation in various centers in the world achieved durable remission of diabetes and independence of exogenous insulin. This review summarizes advantages and risks of this treatment of early diabetes type 1.

Neuroprotective, neurotherapeutic, and neurometabolic effects of carbon monoxide.

PubMed

Mahan, Vicki L

2012-12-27

Studies in animal models show that the primary mechanism by which heme-oxygenases impart beneficial effects is due to the gaseous molecule carbon monoxide (CO). Produced in humans mainly by the catabolism of heme by heme-oxygenase, CO is a neurotransmitter important for multiple neurologic functions and affects several intracellular pathways as a regulatory molecule. Exogenous administration of inhaled CO or carbon monoxide releasing molecules (CORM's) impart similar neurophysiological responses as the endogenous gas. Its' involvement in important neuronal functions suggests that regulation of CO synthesis and biochemical properties may be clinically relevant to neuroprotection and the key may be a change in metabolic substrate from glucose to lactate. Currently, the drug is under development as a therapeutic agent and safety studies in humans evaluating the safety and tolerability of inhaled doses of CO show no clinically important abnormalities, effects, or changes over time in laboratory safety variables. As an important therapeutic option, inhaled CO has entered clinical trials and its clinical role as a neuroprotective and neurotherapeutic agent has been suggested. In this article, we review the neuroprotective effects of endogenous CO and discuss exogenous CO as a neuroprotective and neurotherapeutic agent.

Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

PubMed Central

Makris, Eleftherios A.; Responte, Donald J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2014-01-01

The inability to recapitulate native tissue biomechanics, especially tensile properties, hinders progress in regenerative medicine. To address this problem, strategies have focused on enhancing collagen production. However, manipulating collagen cross-links, ubiquitous throughout all tissues and conferring mechanical integrity, has been underinvestigated. A series of studies examined the effects of lysyl oxidase (LOX), the enzyme responsible for the formation of collagen cross-links. Hypoxia-induced endogenous LOX was applied in multiple musculoskeletal tissues (i.e., cartilage, meniscus, tendons, ligaments). Results of these studies showed that both native and engineered tissues are enhanced by invoking a mechanism of hypoxia-induced pyridinoline (PYR) cross-links via intermediaries like LOX. Hypoxia was shown to enhance PYR cross-linking 1.4- to 6.4-fold and, concomitantly, to increase the tensile properties of collagen-rich tissues 1.3- to 2.2-fold. Direct administration of exogenous LOX was applied in native cartilage and neocartilage generated using a scaffold-free, self-assembling process of primary chondrocytes. Exogenous LOX was found to enhance native tissue tensile properties 1.9-fold. LOX concentration- and time-dependent increases in PYR content (∼16-fold compared with controls) and tensile properties (approximately fivefold compared with controls) of neocartilage were also detected, resulting in properties on par with native tissue. Finally, in vivo subcutaneous implantation of LOX-treated neocartilage in nude mice promoted further maturation of the neotissue, enhancing tensile and PYR content approximately threefold and 14-fold, respectively, compared with in vitro controls. Collectively, these results provide the first report, to our knowledge, of endogenous (hypoxia-induced) and exogenous LOX applications for promoting collagen cross-linking and improving the tensile properties of a spectrum of native and engineered tissues both in vitro and in vivo. PMID:25349395

Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy

PubMed Central

Garcia-Diaz, Beatriz; Garone, Caterina; Barca, Emanuele; Mojahed, Hamed; Gutierrez, Purification; Pizzorno, Giuseppe; Tanji, Kurenai; Arias-Mendoza, Fernando; Quinzii, Caterina M.

2014-01-01

Balanced pools of deoxyribonucleoside triphosphate precursors are required for DNA replication, and alterations of this balance are relevant to human mitochondrial diseases including mitochondrial neurogastrointestinal encephalopathy. In this disease, autosomal recessive TYMP mutations cause severe reductions of thymidine phosphorylase activity; marked elevations of the pyrimidine nucleosides thymidine and deoxyuridine in plasma and tissues, and somatic multiple deletions, depletion and site-specific point mutations of mitochondrial DNA. Thymidine phosphorylase and uridine phosphorylase double knockout mice recapitulated several features of these patients including thymidine phosphorylase activity deficiency, elevated thymidine and deoxyuridine in tissues, mitochondrial DNA depletion, respiratory chain defects and white matter changes. However, in contrast to patients with this disease, mutant mice showed mitochondrial alterations only in the brain. To test the hypothesis that elevated levels of nucleotides cause unbalanced deoxyribonucleoside triphosphate pools and, in turn, pathogenic mitochondrial DNA instability, we have stressed double knockout mice with exogenous thymidine and deoxyuridine, and assessed clinical, neuroradiological, histological, molecular, and biochemical consequences. Mutant mice treated with exogenous thymidine and deoxyuridine showed reduced survival, body weight, and muscle strength, relative to untreated animals. Moreover, in treated mutants, leukoencephalopathy, a hallmark of the disease, was enhanced and the small intestine showed a reduction of smooth muscle cells and increased fibrosis. Levels of mitochondrial DNA were depleted not only in the brain but also in the small intestine, and deoxyribonucleoside triphosphate imbalance was observed in the brain. The relative proportion, rather than the absolute amount of deoxyribonucleoside triphosphate, was critical for mitochondrial DNA maintenance. Thus, our results demonstrate that stress of exogenous pyrimidine nucleosides enhances the mitochondrial phenotype of our knockout mice. Our mouse studies provide insights into the pathogenic role of thymidine and deoxyuridine imbalance in mitochondrial neurogastrointestinal encephalopathy and an excellent model to study new therapeutic approaches. PMID:24727567

Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation

PubMed Central

2014-01-01

Introduction Glutamine rate of appearance (Ra) may be used as an estimate of endogenous glutamine production. Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced, with the potential to allow for multiple assessments of the glutamine Ra over time in critically ill patients, who may not be as metabolically stable as healthy individuals. Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously. Methods Mechanically ventilated patients (n = 11) in the intensive care unit (ICU) were studied on two consecutive days during continuous parenteral feeding. To allow the patients to be used as their own controls, they were randomized for the reference measurement during basal feeding without supplementation, before or after the supplementation period. Glutamine Ra was determined by a bolus injection of 13C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer. Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours. Results A 14% increase of endogenous glutamine Ra was seen at the end of the intravenous supplementation period as compared to the basal measurements (P = 0.009). Conclusions The bolus injection technique to measure glutamine Ra to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements. The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen. PMID:24731231

Globally Important Haptophyte Algae Use Exogenous Pyrimidine Compounds More Efficiently than Thiamin

PubMed Central

Gutowska, Magdalena A.; Shome, Brateen; Sudek, Sebastian; McRose, Darcy L.; Hamilton, Maria; Giovannoni, Stephen J.; Begley, Tadhg P.

2017-01-01

ABSTRACT Vitamin B1 (thiamin) is a cofactor for critical enzymatic processes and is scarce in surface oceans. Several eukaryotic marine algal species thought to rely on exogenous thiamin are now known to grow equally well on the precursor 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP), including the haptophyte Emiliania huxleyi. Because the thiamin biosynthetic capacities of the diverse and ecologically important haptophyte lineage are otherwise unknown, we investigated the pathway in transcriptomes and two genomes from 30 species representing six taxonomic orders. HMP synthase is missing in data from all studied taxa, but the pathway is otherwise complete, with some enzymatic variations. Experiments on axenic species from three orders demonstrated that equivalent growth rates were supported by 1 µM HMP or thiamin amendment. Cellular thiamin quotas were quantified in the oceanic phytoplankter E. huxleyi using the thiochrome assay. E. huxleyi exhibited luxury storage in standard algal medium [(1.16 ± 0.18) × 10−6 pmol thiamin cell−1], whereas quotas in cultures grown under more environmentally relevant thiamin and HMP supplies [(2.22 ± 0.07) × 10−7 or (1.58 ± 0.14) × 10−7 pmol thiamin cell−1, respectively] were significantly lower than luxury values and prior estimates. HMP and its salvage-related analog 4-amino-5-aminomethyl-2-methylpyrimidine (AmMP) supported higher growth than thiamin under environmentally relevant supply levels. These compounds also sustained growth of the stramenopile alga Pelagomonas calceolata. Together with identification of a salvage protein subfamily (TENA_E) in multiple phytoplankton, the results indicate that salvaged AmMP and exogenously acquired HMP are used by several groups for thiamin production. Our studies highlight the potential importance of thiamin pathway intermediates and their analogs in shaping phytoplankton community structure. PMID:29018119

Exogenous Estrogen as Mediator of Racial Differences in Bioactive Insulin-Like Growth Factor-I Levels Among Postmenopausal Women

PubMed Central

Vitolins, Mara Z.; Paskett, Electra D.; Chang, Shine

2015-01-01

Background. The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race–IGF-I relationship in postmenopausal women. Methods. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women’s Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race–IGF-I relationship, we used the Baron–Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Results. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race–IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Conclusions. Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. PMID:25238773

The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.

PubMed

Puntorieri, Valeria; Hiansen, Josh Qua; McCaig, Lynda A; Yao, Li-Juan; Veldhuizen, Ruud A W; Lewis, James F

2013-11-20

Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation. Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours). For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate. The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

Color vision in ADHD: part 2--does attention influence color perception?

PubMed

Kim, Soyeon; Al-Haj, Mohamed; Fuller, Stuart; Chen, Samantha; Jain, Umesh; Carrasco, Marisa; Tannock, Rosemary

2014-10-24

To investigate the impact of exogenous covert attention on chromatic (blue and red) and achromatic visual perception in adults with and without Attention Deficit Hyperactivity Disorder (ADHD). Exogenous covert attention, which is a transient, automatic, stimulus-driven form of attention, is a key mechanism for selecting relevant information in visual arrays. 30 adults diagnosed with ADHD and 30 healthy adults, matched on age and gender, performed a psychophysical task designed to measure the effects of exogenous covert attention on perceived color saturation (blue, red) and contrast sensitivity. The effects of exogenous covert attention on perceived blue and red saturation levels and contrast sensitivity were similar in both groups, with no differences between males and females. Specifically, exogenous covert attention enhanced the perception of blue saturation and contrast sensitivity, but it had no effect on the perception of red saturation. The findings suggest that exogenous covert attention is intact in adults with ADHD and does not account for the observed impairments in the perception of chromatic (blue and red) saturation.

Sulfation of melatonin: enzymatic characterization, differences of organs, species and genders, and bioactivity variation.

PubMed

Tian, Xiangge; Huo, Xiaokui; Dong, Peipei; Wu, Baojian; Wang, Xiaobo; Wang, Chao; Liu, Kexin; Ma, Xiaochi

2015-04-15

Exogenous melatonin (Mel) is widely used in clinic for multiple therapeutic purposes. In metabolism pathways of Mel, 6-hydroxymelatonin-sulfate (S-O-Mel) and N-acetylserotonin sulfate (S-NAS) are the most abundant metabolites account for over 90% of total Mel metabolites in humans, indicating that sulfation plays an important role in reflecting the functions and clearance of Mel in vivo. In the present study, we characterized Mel sulfation using various human organ cytosols (liver, lung, kidney, small intestine and brain), liver cytosols from five different animal species, and cDNA-expressed human sulfotransferase (SULT) for the first time. Our results demonstrated that liver, lung, kidney and small intestine of humans had high catalytic efficiency for Mel sulfation, however, brain contained a very low reaction rate. Interestingly, organ cytosols prepared from females exhibited higher sulfation activity than those of males. SULT isoforms 1A1, 1A2, 1A3, 1B1 and 1E1 exhibited metabolic activities toward Mel. According to kinetic parameters (Km and Vmax), chemical inhibition, correlation analysis, molecular docking and sulfation assays with recombinant human SULTs isoforms, SULT1A1 was determined as the major enzyme responsible for Mel sulfation. Furthermore, considerable species differences in Mel sulfation were observed, and the total intrinsic clearance rate of Mel sulfation was as follows: monkey>rat>dog>human>pig>mouse. Additionally, the anti-inflammatory effects of Mel and its sulfated metabolites were evaluated by inhibiting nitric oxide (NO) production in RAW264.7 cells, and S-O-Mel as a bioactive form, exhibited potent bioactivity. Our investigation provided a global view of the enzyme-dependent sulfation of Mel that can guide biomedical research on Mel. Copyright © 2015 Elsevier Inc. All rights reserved.

[Effect of cadmium stress on physiological characteristics of garlic seedlings and the alleviation effects of exogenous calcium].

PubMed

Li, He; Lian, Hai-feng; Liu, Shi-qi; Yu, Xin-hui; Sun, Ya-li; Guo, Hui-ping

2015-04-01

In the experiment, the effects of exogenous cadmium (Cd2+) and calcium (Ca2+) in nutrient solution on growth, photosynthetic characteristics, enzymes activities, main mineral elements absorption of garlic seedlings were studied. The results showed that cadmium could obviously inhibit the growth of garlic seedlings, decrease the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves, reduced the enzymes (SOD, POD, CAT) activities and increase the MDA content of leaves, and also could reduce the N, P, K, Ca, Mg contents and increase the Cd content of roots. The growth was promoted after adding exogenous calcium to garlic seedlings under cadmium stress, which reflected that the morphological indexes were increased at first and then decreased with the increase of exogenous calcium concentrations, and were maximized when the exogenous calcium was 2 or 3 mmol x L(-1). At the same time, the pigment contents and photosynthetic parameters (P(n), E, g(s)) of leaves showed a similar tendency with the morphological indexes, and they were the highest when the exogenous calcium was 2 or 3 mmol x L(-1). In addition, adding exogenous calcium to garlic seedlings under cadmium stress enhanced the enzymes (SOD, POD, CAT) activities and decreased the MDA content of leaves, also added the N, P, K, Ca, Mg contents and reduced the Cd content of roots, and the effect was best when the exogenous calcium concentration was 2 or 3 mmol x L(-1).

Object-centered representations support flexible exogenous visual attention across translation and reflection.

PubMed

Lin, Zhicheng

2013-11-01

Visual attention can be deployed to stimuli based on our willful, top-down goal (endogenous attention) or on their intrinsic saliency against the background (exogenous attention). Flexibility is thought to be a hallmark of endogenous attention, whereas decades of research show that exogenous attention is attracted to the retinotopic locations of the salient stimuli. However, to the extent that salient stimuli in the natural environment usually form specific spatial relations with the surrounding context and are dynamic, exogenous attention, to be adaptive, should embrace these structural regularities. Here we test a non-retinotopic, object-centered mechanism in exogenous attention, in which exogenous attention is dynamically attracted to a relative, object-centered location. Using a moving frame configuration, we presented two frames in succession, forming either apparent translational motion or in mirror reflection, with a completely uninformative, transient cue presented at one of the item locations in the first frame. Despite that the cue is presented in a spatially separate frame, in both translation and mirror reflection, behavioralperformance in visual search is enhanced when the target in the second frame appears at the same relative location as the cue location than at other locations. These results provide unambiguous evidence for non-retinotopic exogenous attention and further reveal an object-centered mechanism supporting flexible exogenous attention. Moreover, attentional generalization across mirror reflection may constitute an attentional correlate of perceptual generalization across lateral mirror images, supporting an adaptive, functional account of mirror images confusion. Copyright © 2013 Elsevier B.V. All rights reserved.

Object-centered representations support flexible exogenous visual attention across translation and reflection

PubMed Central

Lin, Zhicheng

2013-01-01

Visual attention can be deployed to stimuli based on our willful, top-down goal (endogenous attention) or on their intrinsic saliency against the background (exogenous attention). Flexibility is thought to be a hallmark of endogenous attention, whereas decades of research show that exogenous attention is attracted to the retinotopic locations of the salient stimuli. However, to the extent that salient stimuli in the natural environment usually form specific spatial relations with the surrounding context and are dynamic, exogenous attention, to be adaptive, should embrace these structural regularities. Here we test a non-retinotopic, object-centered mechanism in exogenous attention, in which exogenous attention is dynamically attracted to a relative, object-centered location. Using a moving frame configuration, we presented two frames in succession, forming either apparent translational motion or in mirror reflection, with a completely uninformative, transient cue presented at one of the item locations in the first frame. Despite that the cue is presented in a spatially separate frame, in both translation and mirror reflection, human performance in visual search is enhanced when the target in the second frame appears at the same relative location as the cue location than at other locations. These results provide unambiguous evidence for non-retinotopic exogenous attention and further reveal an object-centered mechanism supporting flexible exogenous attention. Moreover, attentional generalization across mirror reflection may constitute an attentional correlate of perceptual generalization across lateral mirror images, supporting an adaptive, functional account of mirror images confusion. PMID:23942348

The Endogenous-Exogenous Partition in Attribution Theory

ERIC Educational Resources Information Center

Kruglanski, Arie W.

1975-01-01

Within lay explanation of actions, several significant inferences are assumed to follow from the partition between endogenous and exogenous attributions. An endogenous action is judged to constitute an end in itself; an exogenous action is judged to serve as a means to some further end. (Editor/RK)

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

Huang, Er-Wen; Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou; Xue, Sheng-Jiang

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation,more » facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.« less

Explaining Cigarette Smoking: An Endogenous-Exogenous Analysis.

ERIC Educational Resources Information Center

McKillip, Jack

Kruglanski's endogenous-exogenous partition, when applied to reasons given by smokers for smoking cigarettes, distinguishes two types of actions: (1) endogenous reasons implying that the behavior of consuming the cigarette is the goal of the action and the actor is positive toward the behavior, and (2) exogenous reasons implying that the behavior…

Improved exogenous DNA uptake in bovine spermatozoa and gene expression in embryos using membrane destabilizing agents in ICSI-SMGT.

PubMed

Sánchez-Villalba, Esther; Arias, María Elena; Zambrano, Fabiola; Loren, Pía; Felmer, Ricardo

2018-02-01

Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical biotechnological tool for producing transgenic animals. However, transgene expression with this technique in bovine embryos is still inefficient due to low uptake and binding of exogenous DNA in spermatozoa. The present study evaluated the effects of sperm membrane destabilization on the binding capacity, location and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)-SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa including the control. Spermatozoa treated with different membrane destabilizing agents bound the exogenous DNA throughout the head and tail of spermatozoa, compared with the control, in which binding occurred mainly in the post-acrosomal region and tail. The amount of exogenous DNA bound to spermatozoa was much higher for the different sperm treatments than the control (P < 0.05), most likely due to the damage induced by these treatments to the plasma and acrosomal membranes. Exogenous gene expression in embryos was also improved by these treatments. These results demonstrated that sperm membrane destabilization could be a novel strategy in bovine SMGT protocols for the generation of transgenic embryos by ICSI.

Genomic and Epigenomic Insights into Nutrition and Brain Disorders

PubMed Central

Dauncey, Margaret Joy

2013-01-01

Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders. PMID:23503168

Acid-growth response and alpha-expansins in suspension cultures of bright yellow 2 tobacco

NASA Technical Reports Server (NTRS)

Link, B. M.; Cosgrove, D. J.

1998-01-01

The possibility that Bright Yellow 2 (BY2) tobacco (Nicotiana tabacum L.) suspension-cultured cells possess an expansin-mediated acid-growth mechanism was examined by multiple approaches. BY2 cells grew three times faster upon treatment with fusicoccin, which induces an acidification of the cell wall. Exogenous expansins likewise stimulated BY2 cell growth 3-fold. Protein extracted from BY2 cell walls possessed the expansin-like ability to induce extension of isolated walls. In western-blot analysis of BY2 wall protein, one band of 29 kD was recognized by anti-expansin antibody. Six different classes of alpha-expansin mRNA were identified in a BY2 cDNA library. Northern-blot analysis indicated moderate to low abundance of multiple alpha-expansin mRNAs in BY2 cells. From these results we conclude that BY2 suspension-cultured cells have the necessary components for expansin-mediated cell wall enlargement.

Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

PubMed

Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

2015-01-01

We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System

NASA Astrophysics Data System (ADS)

Ouyang, Mengxing; Hill, Winfield; Lee, Jung Hyun; Hur, Soojung Claire

2017-03-01

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

Multiple Transportable Carbohydrates During Exercise: Current Limitations and Directions for Future Research.

PubMed

Wilson, Patrick B

2015-07-01

The concept of multiple transportable carbohydrates (MTC) refers to a combination of saccharides that rely on distinct transporters for intestinal absorption. Ingestion of MTC during prolonged exercise has been purported to increase carbohydrate absorption efficiency, increase exogenous carbohydrate oxidation, reduce gastrointestinal (GI) distress, and improve athletic performance when carbohydrate intake is high (>50-60 g·h⁻¹). Although reviews of MTC research have been published previously, a comprehensive literature evaluation underscoring methodological limitations has not been conducted to guide future work. Accordingly, this review outlined the plausible mechanisms of MTC and subsequently evaluated MTC research based on several factors, including participant characteristics, exercise modality, exercise task, treatment formulation, treatment blinding, and pre-exercise nutrition status. A total of 27 articles examining MTC during exercise were identified and reviewed. Overall, ingestion of MTC led to increased exogenous carbohydrate oxidation, reduced GI distress, and improved performance during cycling lasting ≥2.5 hours, particularly when carbohydrate was ingested at ≥1.2 g·min⁻¹. Despite the apparent benefits, several limitations in the literature were apparent, including that only 3 studies used running, only 2 studies were conducted in the field, most participants were fasted, and women and adolescents were underrepresented. In addition, the majority of the studies fed carbohydrate at ≥1.2 g·min⁻¹, which may have inflated levels of GI distress and exaggerated performance decrements with single-saccharide feedings. Based on these limitations, future MTC investigations should consider focusing on running, examining team-based sports, including women and adolescents, conducting experiments under field conditions, examining the modifying effects of pre-exercise nutrition, and using modest feeding protocols (1.0-1.2 g·min⁻¹).

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss.

PubMed

Galt, Nicholas J; Froehlich, Jacob Michael; Remily, Ethan A; Romero, Sinibaldo R; Biga, Peggy R

2014-09-01

Glucocorticoids (GCs) strongly regulate myostatin expression in mammals via glucocorticoid response elements (GREs), and bioinformatics methods suggest that this regulatory mechanism is conserved among many vertebrates. However, the multiple myostatin genes found in some fishes may be an exception. In silico promoter analyses of the three putative rainbow trout (Oncorhynchus mykiss) myostatin promoters have failed to identify putative GREs, suggesting a divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA expression is not regulated by glucocorticoids in rainbow trout. In this study, both juvenile rainbow trout and primary trout myoblasts were treated with cortisol to examine the effects on myostatin mRNA expression. Results suggest that exogenous cortisol does not regulate myostatin-1a and -1b expression in vivo, as myostatin mRNA levels were not significantly affected by cortisol treatment in either red or white muscle tissue. In red muscle, myostatin-2a levels were significantly elevated in the cortisol treatment group relative to the control, but not the vehicle control, at both 12 h and 24 h post-injection. As such, it is unclear if cortisol was acting alone or in combination with the vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in vitro. Further work is needed to determine if this response is the direct result of cortisol acting on the myostatin-1b promoter or through an alternative mechanism. These results suggest that regulation of myostatin by cortisol may not be as highly conserved as previously thought and support previous work that describes potential functional divergence of the multiple myostatin genes in fishes. Copyright © 2014 Elsevier Inc. All rights reserved.

Cardio-chemical exchange saturation transfer magnetic resonance imaging reveals molecular signatures of endogenous fibrosis and exogenous contrast media.

PubMed

Vandsburger, Moriel; Vandoorne, Katrien; Oren, Roni; Leftin, Avigdor; Mpofu, Senzeni; Delli Castelli, Daniela; Aime, Silvio; Neeman, Michal

2015-01-01

Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST). Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space. cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans. © 2013 American Heart Association, Inc.

A new approach to modeling temperature-related mortality: Non-linear autoregressive models with exogenous input.

PubMed

Lee, Cameron C; Sheridan, Scott C

2018-07-01

Temperature-mortality relationships are nonlinear, time-lagged, and can vary depending on the time of year and geographic location, all of which limits the applicability of simple regression models in describing these associations. This research demonstrates the utility of an alternative method for modeling such complex relationships that has gained recent traction in other environmental fields: nonlinear autoregressive models with exogenous input (NARX models). All-cause mortality data and multiple temperature-based data sets were gathered from 41 different US cities, for the period 1975-2010, and subjected to ensemble NARX modeling. Models generally performed better in larger cities and during the winter season. Across the US, median absolute percentage errors were 10% (ranging from 4% to 15% in various cities), the average improvement in the r-squared over that of a simple persistence model was 17% (6-24%), and the hit rate for modeling spike days in mortality (>80th percentile) was 54% (34-71%). Mortality responded acutely to hot summer days, peaking at 0-2 days of lag before dropping precipitously, and there was an extended mortality response to cold winter days, peaking at 2-4 days of lag and dropping slowly and continuing for multiple weeks. Spring and autumn showed both of the aforementioned temperature-mortality relationships, but generally to a lesser magnitude than what was seen in summer or winter. When compared to distributed lag nonlinear models, NARX model output was nearly identical. These results highlight the applicability of NARX models for use in modeling complex and time-dependent relationships for various applications in epidemiology and environmental sciences. Copyright © 2018 Elsevier Inc. All rights reserved.

Differences in clinical ocular outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix: a systematic review of published literature.

PubMed

Ramírez Soto, Max Carlos

2017-09-28

Sporotrichosis is an implantation mycosis caused by Sporothrix species prevalent worldwide, which occasionally can also result in intraocular infection presenting as an exogenous or endogenous infection (disseminated sporotrichosis). Knowledge in its clinical recognition and management is limited. To systematically review and analyse data from published literature with a view to comparing clinical outcomes between exogenous and endogenous endophthalmitis caused by Sporothrix . Case reports of intraocular sporotrichosis, published from 1960 to 2016, were retrieved from MEDLINE, Embase, Cochrane, LILACS and SciELO databases. The entire data set was divided into two patient groups: (1) exogenous endophthalmitis and (2) endogenous endophthalmitis. Primary outcomes were differences in ocular findings and clinical ocular outcomes between the two groups. From 16 publications retrieved, a total of 8 eyes of 8 patients with exogenous endophthalmitis and 13 eyes of 10 patients with endogenous endophthalmitis were identified. Compared with exogenous endophthalmitis, endogenous endophthalmitis was more common in patients infected with HIV (p=0.001) and those from hyperendemic areas (p=0.036). Anterior uveitis (p=0.015) and posterior uveitis (p=0.04) were more common in the exogenous and endogenous endophthalmitis groups, respectively. The majority of patients with endogenous endophthalmitis had partial or full clinical resolution of ocular lesions with systemic amphotericin B alone or in combination with an oral antifungal, whereas patients with exogenous endophthalmitis had poor outcomes with irreversible vision loss, enucleation and evisceration. Anterior uveitis is more common in exogenous endophthalmitis with worse overall outcomes and complications, compared with endogenous endophthalmitis where posterior uveitis is the most common clinical manifestation, especially in patients infected with HIV and those from hyperendemic areas. Sporothrix infection should be included in the differential diagnosis for ocular inflammation, regardless of the presence or absence of autoimmune comorbidities and whether the patient resides in an endemic area or not. Ophthalmologists should consider intravitreal and systemic antifungal therapy for exogenous and endogenous endophthalmitis caused by Sporothrix . © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Multiple meningiomas].

PubMed

Terrier, L-M; François, P

2016-06-01

Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Differential effects of exogenous and endogenous attention on second-order texture contrast sensitivity

PubMed Central

Barbot, Antoine; Landy, Michael S.; Carrasco, Marisa

2012-01-01

The visual system can use a rich variety of contours to segment visual scenes into distinct perceptually coherent regions. However, successfully segmenting an image is a computationally expensive process. Previously we have shown that exogenous attention—the more automatic, stimulus-driven component of spatial attention—helps extract contours by enhancing contrast sensitivity for second-order, texture-defined patterns at the attended location, while reducing sensitivity at unattended locations, relative to a neutral condition. Interestingly, the effects of exogenous attention depended on the second-order spatial frequency of the stimulus. At parafoveal locations, attention enhanced second-order contrast sensitivity to relatively high, but not to low second-order spatial frequencies. In the present study we investigated whether endogenous attention—the more voluntary, conceptually-driven component of spatial attention—affects second-order contrast sensitivity, and if so, whether its effects are similar to those of exogenous attention. To that end, we compared the effects of exogenous and endogenous attention on the sensitivity to second-order, orientation-defined, texture patterns of either high or low second-order spatial frequencies. The results show that, like exogenous attention, endogenous attention enhances second-order contrast sensitivity at the attended location and reduces it at unattended locations. However, whereas the effects of exogenous attention are a function of the second-order spatial frequency content, endogenous attention affected second-order contrast sensitivity independent of the second-order spatial frequency content. This finding supports the notion that both exogenous and endogenous attention can affect second-order contrast sensitivity, but that endogenous attention is more flexible, benefitting performance under different conditions. PMID:22895879

Exogenous reinfection of tuberculosis in a low-burden area.

PubMed

Schiroli, Consuelo; Carugati, Manuela; Zanini, Fabio; Bandera, Alessandra; Di Nardo Stuppino, Silvia; Monge, Elisa; Morosi, Manuela; Gori, Andrea; Matteelli, Alberto; Codecasa, Luigi; Franzetti, Fabio

2015-12-01

Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis.

PubMed

Zhou, S; Wang, Z; Tang, J; Li, W; Huang, J; Xu, W; Luo, F; Xu, M; Wang, J; Wen, X; Chen, L; Chen, H; Su, N; Shen, Y; Du, X; Xie, Y; Chen, L

2016-12-01

The aim of the present study is to investigate the effects of exogenous fibroblast growth factor (FGF)9 on the progression of post-traumatic osteoarthritis (OA). The expression of FGF9 in articular cartilage with OA is detected by immunohistochemistry (IHC). The effects of intra-articular exogenous FGF9 injection on post-traumatic OA induced by the destabilization of the medial meniscus (DMM) surgery are evaluated. Cartilage changes and osteophyte formation in knee joints are investigated by histological analysis. Changes in subchondral bone are evaluated by microcomputed tomography (micro-CT). The effect of exogenous FGF9 on an interleukin-1β (IL-1β)-induced ex vivo OA model of human articular cartilage tissues is also evaluated. FGF9 expression was down-regulated in articular chondrocytes of OA but ectopically induced at sites of osteophyte formation. Intra-articular injection of exogenous FGF9 attenuated articular cartilage degradation in mice after DMM surgery. Exogenous FGF9 suppressed collagen X and MMP13 expressions in OA cartilage, while promoted collagen II expression. Similar results were observed in IL-1β-induced ex vivo OA model. Intra-articular injection of FGF9 had no significant effect on the subchondral bone of knee joints after DMM surgery, but aggravated osteophyte formation. The expressions of SOX9 and collagen II, and cell proliferation were up-regulated at sites of initial osteophyte formation in mice with exogenous FGF9 treatment. Intra-articular injection of exogenous FGF9 delays articular cartilage degradation in post-traumatic OA, while aggravates osteophyte formation. Copyright © 2016. Published by Elsevier Ltd.

Exogenously applied spermidine alleviates photosynthetic inhibition under drought stress in maize (Zea mays L.) seedlings associated with changes in endogenous polyamines and phytohormones.

PubMed

Li, Lijie; Gu, Wanrong; Li, Jing; Li, Congfeng; Xie, Tenglong; Qu, Danyang; Meng, Yao; Li, Caifeng; Wei, Shi

2018-05-15

Drought stress (DS) is a major environmental factor limiting plant growth and crop productivity worldwide. It has been established that exogenous spermidine (Spd) stimulates plant tolerance to DS. The effects of exogenous Spd on plant growth, photosynthetic performance, and chloroplast ultrastructure as well as changes in endogenous polyamines (PAs) and phytohormones were investigate in DS-resistant (Xianyu 335) and DS-sensitive (Fenghe 1) maize seedlings under well-watered and DS treatments. Exogenous Spd alleviated the stress-induced reduction in growth, photosynthetic pigment content, photosynthesis rate (P n ) and photochemical quenching (q P ) parameters, including the maximum photochemistry efficiency of photosystem II (PSII) (F v /F m ), PSII operating efficiency (ФPSII), and qP coefficient. Exogenous Spd further enhanced stress-induced elevation in non-photochemical quenching (NPQ) and the de-epoxidation state of the xanthophyll cycle (DEPS). Microscopic analysis revealed that seedlings displayed a more ordered arrangement of chloroplast ultrastructure upon Spd application during DS. Exogenous Spd increased the endogenous PA concentrations in the stressed plants. Additionally, exogenous Spd increased indoleacetic acid (IAA), zeatin riboside (ZR) and gibberellin A 3 (GA 3 ) and decreased salicylic acid (SA) and jasmonate (JA) concentrations under DS. These results indicate that exogenous Spd can alleviate the growth inhibition and damage to the structure and function of the photosynthetic apparatus caused by DS and that this alleviation may be associated with changes in endogenous PAs and phytohormones. This study contributes to advances in the knowledge of Spd-induced drought tolerance. Copyright © 2018. Published by Elsevier Masson SAS.

The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia.

PubMed

He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

2015-08-25

Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca(2+) and K(+) in root cells by increasing the activity of plasma membrane (PM) H(+)-ATPase and tonoplast H(+)-ATPase and H(+)-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber.

Exogenous estrogen as mediator of racial differences in bioactive insulin-like growth factor-I levels among postmenopausal women.

PubMed

Jung, Su Yon; Vitolins, Mara Z; Paskett, Electra D; Chang, Shine

2015-04-01

The role of exogenous estrogen use in racial differences in insulin-like growth factor-I (IGF-I) levels which affect cancer risk is unclear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins was mediated by exogenous estrogen and the extent to which exogenous estrogen influenced the race-IGF-I relationship in postmenopausal women. This cross-sectional study included 636 white and 133 African American postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study. To assess exogenous estrogen use (nonusers [n = 262] vs users [n = 507]) as a mediator of the race-IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odd ratios for IGF-I levels on race plus a bootstrapping test for the significance of the mediation effect. Compared with white women, African American women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. Among oral contraceptive ever users, exogenous estrogen had a strong mediation effect (67%; p = .018) in the race-IGF-I relationship. In the women with a history of hypertension, exogenous estrogen explained racial differences in IGF-I levels to a modest degree (23%; p = .029). Exogenous estrogen use has a potentially important role in disparities in IGF-I bioactivity between postmenopausal African American and white women. A history of oral contraceptive use and hypertension may be part of the interconnected hormonal pathways related to racial differences in IGF-I levels. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Robust Neurite Extension Following Exogenous Electrical Stimulation within Single Walled Carbon Nanotube-Composite Hydrogels

PubMed Central

Koppes, A. N.; Keating, K. W.; McGregor, A. L.; Koppes, R. A.; Kearns, K. R.; Ziemba, A. M.; McKay, C. A.; Zuidema, J. M.; Rivet, C. J.; Gilbert, R. J.; Thompson, D. M.

2016-01-01

The use of exogenous electrical stimulation to promote nerve regeneration has achieved only limited success. Conditions impeding optimized outgrowth may arise from inadequate stimulus presentation due to differences in injury geometry or signal attenuation. Implantation of an electrically-conductive biomaterial may mitigate this attenuation and provide a more reproducible signal. In this study, a conductive nanofiller (single-walled carbon nanotubes [SWCNT]) was selected as one possible material to manipulate the bulk electrical properties of a collagen type I-10% Matrigel™ composite hydrogel. Neurite outgrowth within hydrogels (SWCNT or nanofiller-free controls) was characterized to determine if: 1) nanofillers influence neurite extension and 2) electrical stimulation of the nanofiller composite hydrogel enhances neurite outgrowth. Increased SWCNT loading (10–100-μg/ml) resulted in greater bulk conductivity (up to 1.7-fold) with no significant changes to elastic modulus. Neurite outgrowth increased 3.3-fold in 20-μg/mL SWCNT loaded biomaterials relative to the nanofiller-free control. Electrical stimulation promoted greater outgrowth (2.9-fold) within SWCNT-free control. The concurrent presentation of electrical stimulation and SWCNT-loaded biomaterials resulted in a 7.0-fold increase in outgrowth relative to the unstimulated, nanofiller-free controls. Local glia residing within the DRG likely contribute, in part, to the observed increases in outgrowth; but it is unknown which specific nanofiller properties influence neurite extension. Characterization of neuronal behavior in model systems, such as those described here, will aid the rational development of biomaterials as well as the appropriate delivery of electrical stimuli to support nerve repair. PMID:27167609

Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC12 neurons in vitro

PubMed Central

Nusshold, Christoph; Kollroser, Manfred; Köfeler, Harald; Rechberger, Gerald; Reicher, Helga; Üllen, Andreas; Bernhart, Eva; Waltl, Sabine; Kratzer, Ingrid; Hermetter, Albin; Hackl, Hubert; Trajanoski, Zlatko; Hrzenjak, Andelko; Malle, Ernst; Sattler, Wolfgang

2014-01-01

Recent observations link myeloperoxidase (MPO) activation to neurodegeneration. In multiple sclerosis MPO is present in areas of active demyelination where the potent oxidant hypochlorous acid (HOCl), formed by MPO from H2O2 and chloride ions, could oxidatively damage myelin-associated lipids. The purpose of this study was (i) to characterize reaction products of sphingomyelin (SM) formed in response to modification by HOCl, (ii) to define the impact of exogenously added SM and HOCl-modified SM (HOCl-SM) on viability parameters of a neuronal cell line (PC12), and (iii) to study alterations in the PC12 cell proteome in response to SM and HOCl-SM. MALDI-TOF-MS analyses revealed that HOCl, added as reagent or generated enzymatically, transforms SM into chlorinated species. On the cellular level HOCl-SM but not SM induced the formation of reactive oxygen species. HOCl-SM induced severely impaired cell viability, dissipation of the mitochondrial membrane potential, and activation of caspase-3 and DNA damage. Proteome analyses identified differential expression of specific subsets of proteins in response to SM and HOCl-SM. Our results demonstrate that HOCl modification of SM results in the generation of chlorinated lipid species with potent neurotoxic properties. Given the emerging connections between the MPO–H2O2–chloride axis and neurodegeneration, this chlorinating pathway might be implicated in neuropathogenesis. PMID:20226853

Th17 cells and CD4(+) multifunctional T cells in patients with systemic lupus erythematosus.

PubMed

Araújo, Júlio Antônio Pereira; Mesquita, Danilo; de Melo Cruvinel, Wilson; Salmazi, Karina Inácio; Kallás, Esper Georges; Andrade, Luis Eduardo Coelho

2016-01-01

Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i.e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4(+) T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4(+) T cells analyzed. We found that SLE patients presented a decreased number of total CD4(+) cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

PubMed

Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

2012-01-01

Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

Characterization and in vivo regulon determination of an ECF sigma factor and its cognate anti-sigma factor in Nostoc punctiforme.

PubMed

Bell, Nicole; Lee, Jamie J; Summers, Michael L

2017-04-01

Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress. A sigG mutant was unable to survive envelope damage caused by heat or EDTA, but was able to form functional heterocysts. Akinetes in the mutant strain appeared normal, but these cultures were less resistant to lysozyme and cold treatments than those of the wild-type strain. The SigG in vivo regulon was determined before and during akinete differentiation using DNA microarray analysis, and found to include multiple genes with putative association to the cell envelope. Mapped promoters common to both arrays enabled identification of a SigG promoter-binding motif that was supported in vivo by reporter studies, and in vitro by run-off transcription experiments. These findings support SigG/SapG as a sigma/anti-sigma pair involved in repair of envelope damage resulting from exogenous sources or cellular differentiation. © 2017 John Wiley & Sons Ltd.

Assessment of glycemic response to an oral glucokinase activator in a proof of concept study: application of a semi-mechanistic, integrated glucose-insulin-glucagon model.

PubMed

Schneck, Karen B; Zhang, Xin; Bauer, Robert; Karlsson, Mats O; Sinha, Vikram P

2013-02-01

A proof of concept study was conducted to investigate the safety and tolerability of a novel oral glucokinase activator, LY2599506, during multiple dose administration to healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). To analyze the study data, a previously established semi-mechanistic integrated glucose-insulin model was extended to include characterization of glucagon dynamics. The model captured endogenous glucose and insulin dynamics, including the amplifying effects of glucose on insulin production and of insulin on glucose elimination, as well as the inhibitory influence of glucose and insulin on hepatic glucose production. The hepatic glucose production in the model was increased by glucagon and glucagon production was inhibited by elevated glucose concentrations. The contribution of exogenous factors to glycemic response, such as ingestion of carbohydrates in meals, was also included in the model. The effect of LY2599506 on glucose homeostasis in subjects with T2DM was investigated by linking a one-compartment, pharmacokinetic model to the semi-mechanistic, integrated glucose-insulin-glucagon system. Drug effects were included on pancreatic insulin secretion and hepatic glucose production. The relationships between LY2599506, glucose, insulin, and glucagon concentrations were described quantitatively and consequently, the improved understanding of the drug-response system could be used to support further clinical study planning during drug development, such as dose selection.

A mitochondrial alkaline/neutral invertase isoform (A/N-InvC) functions in developmental energy-demanding processes in Arabidopsis.

PubMed

Martín, Mariana L; Lechner, Leandra; Zabaleta, Eduardo J; Salerno, Graciela L

2013-03-01

Recent findings demonstrate that alkaline/neutral invertases (A/N-Invs), enzymes that catalyze the breakdown of sucrose into glucose and fructose, are essential proteins in plant life. The fact that different isoforms are present in multiple locations makes them candidates for the coordination of metabolic processes. In the present study, we functionally characterized the encoding gene of a novel A/N-Inv (named A/N-InvC) from Arabidopsis, which localizes in mitochondria. A/N-InvC is expressed in roots, in aerial parts (shoots and leaves) and flowers. A detailed phenotypic analysis of knockout mutant plants (invc) reveals an impaired growth phenotype. Shoot growth was severely reduced, but root development was not affected as reported for A/N-InvA mutant (inva) plants. Remarkably, germination and flowering, two energy demanding processes, were the most affected stages. The effect of exogenous growth regulators led us to suggest that A/N-InvC may be modulating hormone balance in relation to the radicle emergence. We also show that oxygen consumption is reduced in inva and invc in comparison with wild-type plants, indicating that both organelle isoenzymes may play a fundamental role in mitochondrion functionality. Taken together, our results emphasize the involvement of mitochondrial A/N-Invs in developmental processes and uncover the possibility of playing different roles for the two isoforms located in the organelle.

A Role of Phase-Resetting in Coordinating Large Scale Neural Networks During Attention and Goal-Directed Behavior

PubMed Central

Voloh, Benjamin; Womelsdorf, Thilo

2016-01-01

Short periods of oscillatory activation are ubiquitous signatures of neural circuits. A broad range of studies documents not only their circuit origins, but also a fundamental role for oscillatory activity in coordinating information transfer during goal directed behavior. Recent studies suggest that resetting the phase of ongoing oscillatory activity to endogenous or exogenous cues facilitates coordinated information transfer within circuits and between distributed brain areas. Here, we review evidence that pinpoints phase resetting as a critical marker of dynamic state changes of functional networks. Phase resets: (1) set a “neural context” in terms of narrow band frequencies that uniquely characterizes the activated circuits; (2) impose coherent low frequency phases to which high frequency activations can synchronize, identifiable as cross-frequency correlations across large anatomical distances; (3) are critical for neural coding models that depend on phase, increasing the informational content of neural representations; and (4) likely originate from the dynamics of canonical E-I circuits that are anatomically ubiquitous. These multiple signatures of phase resets are directly linked to enhanced information transfer and behavioral success. We survey how phase resets re-organize oscillations in diverse task contexts, including sensory perception, attentional stimulus selection, cross-modal integration, Pavlovian conditioning, and spatial navigation. The evidence we consider suggests that phase-resets can drive changes in neural excitability, ensemble organization, functional networks, and ultimately, overt behavior. PMID:27013986

Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system.

PubMed

Pelá, I R; Ferreira, M E; Melo, M C; Silva, C A; Coelho, M M; Valenzuela, C F

2000-05-01

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289-293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3-4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

Polyethylenimine carbon nanotube fiber electrodes for enhanced detection of neurotransmitters.

PubMed

Zestos, Alexander G; Jacobs, Christopher B; Trikantzopoulos, Elefterios; Ross, Ashley E; Venton, B Jill

2014-09-02

Carbon nanotube (CNT)-based microelectrodes have been investigated as alternatives to carbon-fiber microelectrodes for the detection of neurotransmitters because they are sensitive, exhibit fast electron transfer kinetics, and are more resistant to surface fouling. Wet spinning CNTs into fibers using a coagulating polymer produces a thin, uniform fiber that can be fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have been used as microelectrodes to detect dopamine, serotonin, and hydrogen peroxide. In this study, we characterize microelectrodes with CNT fibers made in polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers. PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The currents for dopamine were adsorption controlled at PEI-CNT fiber microelectrodes, independent of scan repetition frequency, and stable for over 10 h. PEI-CNT fiber microelectrodes were resistant to surface fouling by serotonin and the metabolite interferant 5-hydroxyindoleacetic acid (5-HIAA). No change in sensitivity was observed for detection of serotonin after 30 flow injection experiments or after 2 h in 5-HIAA for PEI-CNT electrodes. The antifouling properties were maintained in brain slices when serotonin was exogenously applied multiple times or after bathing the slice in 5-HIAA. Thus, PEI-CNT fiber electrodes could be useful for the in vivo monitoring of neurochemicals.

Chicken-type lysozyme functions in the antibacterial immunity in red swamp crayfish, Procambarus clarkii.

PubMed

Liao, Tian-Jiang; Gao, Jie; Wang, Jin-Xing; Wang, Xian-Wei

2018-08-01

Lysozymes possess antibacterial activities, making them crucial defense proteins in innate immunity. In this study, a chicken-type (c-type) lysozyme (designated PcLyzc) was cloned and characterized from red swamp crayfish Procambarus clarkii. The full-length cDNA had an open reading frame of 435 base pairs encoding a polypeptide of 144 amino acid residues. Multiple alignments and phylogenetic analysis revealed that PcLyzc shared high similarity to the other known invertebrate c-type lysozymes. PcLyzc transcripts were steadily expressed in a wide range of tissues in healthy crayfish, and were prominently up-regulated in the hepatopancreas and gills after Vibrio anguillarum or Aeromonas hydrophila challenge. Recombinant PcLyzc showed inhibitory activity in vitro against both Gram-positive bacteria, including Staphylococcus aureus, Micrococcus luteus and Bacillus thuringiensis, and Gram-negative bacteria, including A. hydrophila, V. anguillarum and Escherichia coli. By overexpressing PcLyzc through introducing exogenous recombinant protein, or silencing PcLyzc expression through injecting double strand RNA, it was found that PcLyzc could help eliminate the invading bacteria in crayfish hemolymph and could protect crayfish from death, possibly by promoting the hemocytic phagocytosis. These results indicated that PcLyzc played a role in the antibacterial immunity of crustaceans, and laid a foundation of developing new therapeutic agents in aquaculture. Copyright © 2018 Elsevier Ltd. All rights reserved.

Yap is essential for retinal progenitor cell cycle progression and RPE cell fate acquisition in the developing mouse eye.

PubMed

Kim, Jin Young; Park, Raehee; Lee, Jin Hwan J; Shin, Jinyeon; Nickas, Jenna; Kim, Seonhee; Cho, Seo-Hee

2016-11-15

Yap functions as a transcriptional regulator by acting together with sequence-specific DNA binding factors and transcription cofactors to mediate cell proliferation in developing epithelial tissues and tumors. An upstream kinase cascade controls nuclear localization and function in response to partially identified exogenous signals, including cell-to-cell contact. Nevertheless, its role in CNS development is poorly understood. In order to investigate Yap function in developing CNS, we characterized the cellular outcomes after selective Yap gene ablation in developing ocular tissues. When Yap was lost, presumptive retinal pigment epithelium acquired anatomical and molecular characteristics resembling those of the retinal epithelium rather than of RPE, including loss of pigmentation, pseudostratified epithelial morphology and ectopic induction of markers for retinal progenitor cells, like Chx10, and neurons, like β-Tubulin III. In addition, developing retina showed signs of progressive degeneration, including laminar folding, thinning and cell loss, which resulted from multiple defects in cell proliferation and survival, and in junction integrity. Furthermore, Yap-deficient retinal progenitors displayed decreased S-phase cells and altered cell cycle progression. Altogether, our studies not only illustrate the canonical function of Yap in promoting the proliferation of progenitors, but also shed new light on its evolutionarily conserved, instructive role in regional specification, maintenance of junctional integrity and precise regulation of cell proliferation during neuroepithelial development. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization and in vivo regulon determination of an ECF sigma factor and its cognate anti-sigma factor in Nostoc punctiforme

PubMed Central

Bell, Nicole; Lee, Jamie J.; Summers, Michael L.

2017-01-01

Summary Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress. A sigG mutant was unable to survive envelope damage caused by heat or EDTA, but was able to form functional heterocysts. Akinetes in the mutant strain appeared normal, but these cultures were less resistant to lysozyme and cold treatments than those of the wild-type strain. The SigG in vivo regulon was determined before and during akinete differentiation using DNA microarray analysis, and found to include multiple genes with putative association to the cell envelope. Mapped promoters common to both arrays enabled identification of a SigG promoter-binding motif that was supported in vivo by reporter studies, and in vitro by run-off transcription experiments. These findings support SigG/SapG as a sigma/anti-sigma pair involved in repair of envelope damage resulting from exogenous sources or cellular differentiation. PMID:28105698

In-gel multiple displacement amplification of long DNA fragments diluted to the single molecule level.

PubMed

Michikawa, Yuichi; Sugahara, Keisuke; Suga, Tomo; Ohtsuka, Yoshimi; Ishikawa, Kenichi; Ishikawa, Atsuko; Shiomi, Naoko; Shiomi, Tadahiro; Iwakawa, Mayumi; Imai, Takashi

2008-12-15

The isolation and multiple genotyping of long individual DNA fragments are needed to obtain haplotype information for diploid organisms. Limiting dilution of sample DNA followed by multiple displacement amplification is a useful technique but is restricted to short (<5 kb) DNA fragments. In the current study, a novel modification was applied to overcome these problems. A limited amount of cellular DNA was carefully released from intact cells into a mildly heated alkaline agarose solution and mixed thoroughly. The solution was then gently aliquoted and allowed to solidify while maintaining the integrity of the diluted DNA. Exogenously provided Phi29 DNA polymerase was used to perform consistent genomic amplification with random hexameric oligonucleotides within the agarose gels. Simple heat melting of the gel allowed recovery of the amplified materials in a solution of the polymerase chain reaction (PCR)-ready form. The haplotypes of seven SNPs spanning 240 kb of the DNA surrounding the human ATM gene region on chromosome 11 were determined for 10 individuals, demonstrating the feasibility of this new method.

Measurement of endogenous versus exogenous formaldehyde-induced DNA-protein crosslinks in animal tissues by stable isotope labeling and ultrasensitive mass spectrometry

PubMed Central

Lai, Yongquan; Yu, Rui; Hartwell, Hadley J.; Moeller, Benjamin C.; Bodnar, Wanda M.; Swenberg, James A.

2016-01-01

DNA-protein crosslinks (DPCs) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Due to their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally-specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([13CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous (13CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues, but were absent in tissues distant to the site of contact. This observation together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde, and may inform improved disease prevention and treatment strategies. PMID:26984759

A method for tracing exogenous DNA uptake in live spermatozoa and embryos.

PubMed

Mu, Y; Jiao, M; Zhao, Y; Lv, J; Wang, J; Hao, J; Zhang, X; Kong, Q; Liu, Z

2018-03-01

Sperm-mediated gene transfer(SMGT) is a simple method for producing transgenic animals. Due to the lack of repeatability in spermatozoa binding and internalization of exogenous DNA, the efficiency of SMGT is still low. Considering this point, the present work aims to develop a method for evaluating the spermatozoa capacity of binding exogenous DNA after co-incubation with DNA. The main approach is using a Cy5-labelled DNA to trace the exogenous DNA and assess the ability of spermatozoa to take up exogenous DNA. Using this technique, we found that the percentage of spermatozoa that are binding and uptaking DNA is higher at concentration of 10 μg/mL and 100 μg/mL than 5 μg/mL, 1 μg/mL and 0 μg/mL after incubation with Cy5-DNA for 30min at 37oC. After fertilization, the DNA fluorescence signal was also detected in zygotes in groups where spermatozoa were incubated with 10 μg/mL and 100 μg/mL of Cy5-DNA. These results showed a simple and convenient method to trace the exogenous DNA in spermatozoa and zygote when compared to conventional methods of labeling DNA during fertilization, resulting in a real-time observation of the exogenous DNA in spermatozoa and zygote. Copyright© by the Polish Academy of Sciences.

Visible propagation from invisible exogenous cueing.

PubMed

Lin, Zhicheng; Murray, Scott O

2013-09-20

Perception and performance is affected not just by what we see but also by what we do not see-inputs that escape our awareness. While conscious processing and unconscious processing have been assumed to be separate and independent, here we report the propagation of unconscious exogenous cueing as determined by conscious motion perception. In a paradigm combining masked exogenous cueing and apparent motion, we show that, when an onset cue was rendered invisible, the unconscious exogenous cueing effect traveled, manifesting at uncued locations (4° apart) in accordance with conscious perception of visual motion; the effect diminished when the cue-to-target distance was 8° apart. In contrast, conscious exogenous cueing manifested in both distances. Further evidence reveals that the unconscious and conscious nonretinotopic effects could not be explained by an attentional gradient, nor by bottom-up, energy-based motion mechanisms, but rather they were subserved by top-down, tracking-based motion mechanisms. We thus term these effects mobile cueing. Taken together, unconscious mobile cueing effects (a) demonstrate a previously unknown degree of flexibility of unconscious exogenous attention; (b) embody a simultaneous dissociation and association of attention and consciousness, in which exogenous attention can occur without cue awareness ("dissociation"), yet at the same time its effect is contingent on conscious motion tracking ("association"); and (c) underscore the interaction of conscious and unconscious processing, providing evidence for an unconscious effect that is not automatic but controlled.

Endogenous versus exogenous shocks in systems with memory

NASA Astrophysics Data System (ADS)

Sornette, D.; Helmstetter, A.

2003-02-01

Systems with long-range persistence and memory are shown to exhibit different precursory as well as recovery patterns in response to shocks of exogenous versus endogenous origins. By endogenous, we envision either fluctuations resulting from an underlying chaotic dynamics or from a stochastic forcing origin which may be external or be an effective coarse-grained description of the microscopic fluctuations. In this scenario, endogenous shocks result from a kind of constructive interference of accumulated fluctuations whose impacts survive longer than the large shocks themselves. As a consequence, the recovery after an endogenous shock is in general slower at early times and can be at long times either slower or faster than after an exogenous perturbation. This offers the tantalizing possibility of distinguishing between an endogenous versus exogenous cause of a given shock, even when there is no “smoking gun”. This could help in investigating the exogenous versus self-organized origins in problems such as the causes of major biological extinctions, of change of weather regimes and of the climate, in tracing the source of social upheaval and wars, and so on. Sornette et al., Volatility fingerprints of large stocks: endogenous versus exogenous, cond-mat/0204626 has already shown how this concept can be applied concretely to differentiate the effects on financial markets of the 11 September 2001 attack or of the coup against Gorbachev on 19 August 1991 (exogenous) from financial crashes such as October 1987 (endogenous).

Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

PubMed

Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

2017-03-01

To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

Distribution of calcium (Ca) and magnesium (Mg) in the leaves of Brassica rapa under varying exogenous Ca and Mg supply.

PubMed

Rios, Juan Jose; Lochlainn, Seosamh O; Devonshire, Jean; Graham, Neil S; Hammond, John P; King, Graham J; White, Philip J; Kurup, Smita; Broadley, Martin R

2012-05-01

Leafy vegetable Brassica crops are an important source of dietary calcium (Ca) and magnesium (Mg) and represent potential targets for increasing leaf Ca and Mg concentrations through agronomy or breeding. Although the internal distribution of Ca and Mg within leaves affects the accumulation of these elements, such data are not available for Brassica. The aim of this study was to characterize the internal distribution of Ca and Mg in the leaves of a vegetable Brassica and to determine the effects of altered exogenous Ca and Mg supply on this distribution. Brassica rapa ssp. trilocularis 'R-o-18' was grown at four different Ca:Mg treatments for 21 d in a controlled environment. Concentrations of Ca and Mg were determined in fully expanded leaves using inductively coupled plasma-mass spectrometry (ICP-MS). Internal distributions of Ca and Mg were determined in transverse leaf sections at the base and apex of leaves using energy-dispersive X-ray spectroscopy (EDS) with cryo-scanning electron microscopy (cryo-SEM). Leaf Ca and Mg concentrations were greatest in palisade and spongy mesophyll cells, respectively, although this was dependent on exogenous supply. Calcium accumulation in palisade mesophyll cells was enhanced slightly under high Mg supply; in contrast, Mg accumulation in spongy mesophyll cells was not affected by Ca supply. The results are consistent with Arabidopsis thaliana and other Brassicaceae, providing phenotypic evidence that conserved mechanisms regulate leaf Ca and Mg distribution at a cellular scale. The future study of Arabidopsis gene orthologues in mutants of this reference B. rapa genotype will improve our understanding of Ca and Mg homeostasis in plants and may provide a model-to-crop translation pathway for targeted breeding.

Bioavailable Insulin-Like Growth Factor-I Inversely Related to Weight Gain in Postmenopausal Women regardless of Exogenous Estrogen

PubMed Central

Jung, Su Yon; Hursting, Stephen D.; Guindani, Michele; Vitolins, Mara Z.; Paskett, Electra; Chang, Shine

2014-01-01

Background Weight gain, insulin-like growth factor-I (IGF-I) levels, and excess exogenous steroid hormone use are putative cancer risk factors, yet their interconnected pathways have not been fully characterized. This cross-sectional study investigated the relationship between plasma IGF-I levels and weight gain according to body mass index (BMI), leptin levels, and exogenous estrogen use among postmenopausal women. Methods This study included 794 postmenopausal women who enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. The relationship between IGF-I levels and weight gain was analyzed using ordinal logistic regression. We used the molar ratio of IGF-I to IGF binding protein-3 (IGF-I/IGFBP-3) or circulating IGF-I levels adjusting for IGFBP-3 as a proxy of bioavailable IGF-I. The plasma concentrations were expressed as quartiles. Results Among the obese group, women in the third quartile (Q3) of IGF-I and highest quartile of IGF-I/IGFBP-3 were less likely to gain weight (>3% from baseline) than were women in the first quartiles (Q1). Among the normal weight group, women in Q2 and Q3 of IGF-I/IGFBP-3 were 70% less likely than those in Q1 to gain weight. Among current estrogen users, Q3 of IGF-I/IGFBP-3 had 0.5 times the odds of gaining weight than Q1. Conclusions Bioavailable IGF-I levels were inversely related to weight gain overall. Impact Although weight gain was not consistent with increases in IGF-I levels among postmenopausal women in this report, avoidance of weight gain as a strategy to reduce cancer risk may be recommend. PMID:24363252

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

PubMed

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A

2016-01-15

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated "CiHHV-6A/B". These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections.

Changes in digestive enzyme activities during larval development of leopard grouper (Mycteroperca rosacea).

PubMed

Martínez-Lagos, R; Tovar-Ramírez, D; Gracia-López, V; Lazo, J P

2014-06-01

The leopard grouper is an endemic species of the Mexican Pacific with an important commercial fishery and good aquaculture potential. In order to assess the digestive capacity of this species during the larval period and aid in the formulation of adequate weaning diets, this study aimed to characterize the ontogeny of digestive enzymes during development of the digestive system. Digestive enzymes trypsin, chymotrypsin, acid protease, leucine-alanine peptidase, alkaline phosphatase, aminopeptidase N, lipase, amylase and maltase were quantified in larvae fed live prey and weaned onto a formulated microdiet at 31 days after hatching (DAH) and compared with fasting larvae. Enzyme activity for trypsin, lipase and amylase were detected before the opening of the mouth and the onset of exogenous feeding, indicating a precocious development of the digestive system that has been described in many fish species. The intracellular enzyme activity of leucine-alanine peptidase was high during the first days of development, with a tendency to decrease as larvae developed, reaching undetectable levels at the end of the experimental period. In contrast, activities of enzymes located in the intestinal brush border (i.e., aminopeptidase and alkaline phosphatase) were low at the start of exogenous feeding but progressively increased with larval development, indicating the gradual maturation of the digestive system. Based on our results, we conclude that leopard grouper larvae possess a functional digestive system at hatching and before the onset of exogenous feeding. The significant increase in the activity of trypsin, lipase, amylase and acid protease between 30 and 40 DAH suggests that larvae of this species can be successfully weaned onto microdiets during this period.

[Normal and abnormal skin color].

PubMed

Ortonne, J-P

2012-11-01

The varieties of normal skin color in humans range from people of "no color" (pale white) to "people of color" (light brown, dark brown, and black). Skin color is a blend resulting from the skin chromophores red (oxyhaemoglobin), blue (deoxygenated haemoglobin), yellow-orange (carotene, an exogenous pigment), and brown (melanin). Melanin, however, is the major component of skin color ; it is the presence or absence of melanin in the melanosomes in melanocytes and melanin in keratinocytes that is responsible for epidermal pigmentation, and the presence of melanin in macrophages or melanocytes in the dermis that is responsible for dermal pigmentation. Two groups of pigmentary disorders are commonly distinguished: the disorders of the quantitative and qualitative distribution of normal pigment and the abnormal presence of exogenous or endogenous pigments in the skin. The first group includes hyperpigmentations, which clinically manifest by darkening of the skin color, and leukodermia, which is characterized by lightening of the skin. Hypermelanosis corresponds to an overload of melanin or an abnormal distribution of melanin in the skin. Depending on the color, melanodermia (brown/black) and ceruloderma (blue/grey) are distinguished. Melanodermia correspond to epidermal hypermelanocytosis (an increased number of melanocytes) or epidermal hypermelanosis (an increase in the quantity of melanin in the epidermis with no modification of the number of melanocytes). Ceruloderma correspond to dermal hypermelanocytosis (abnormal presence in the dermis of cells synthesizing melanins) ; leakage in the dermis of epidermal melanin also exists, a form of dermal hypermelanosis called pigmentary incontinence. Finally, dyschromia can be related to the abnormal presence in the skin of a pigment of exogenous or endogenous origin. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

PubMed

Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

2016-02-01

The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. © 2015 The Author(s).

Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

PubMed

Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

Genetic and functional studies of the intervertebral disc: a novel murine intervertebral disc model.

PubMed

Pelle, Dominic W; Peacock, Jacqueline D; Schmidt, Courtney L; Kampfschulte, Kevin; Scholten, Donald J; Russo, Scott S; Easton, Kenneth J; Steensma, Matthew R

2014-01-01

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.

Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

PubMed Central

Pelle, Dominic W.; Peacock, Jacqueline D.; Schmidt, Courtney L.; Kampfschulte, Kevin; Scholten, Donald J.; Russo, Scott S.; Easton, Kenneth J.; Steensma, Matthew R.

2014-01-01

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration. PMID:25474689

Human mesenchymal stem cells generate a distinct pericellular zone of MMP activities via binding of MMPs and secretion of high levels of TIMPs.

PubMed

Lozito, Thomas P; Jackson, Wesley M; Nesti, Leon J; Tuan, Rocky S

2014-02-01

Mesenchymal stem cells (MSCs) are attractive candidates for inclusion in cell-based therapies by virtue of their abilities to home to wound sites. However, in-depth characterization of the specific effects of MSCs on their microenvironments is needed to realize their full therapeutic potentials. Furthermore, since MSCs of varying properties can be isolated from a diverse spectrum of tissues, a strategic and rational approach in MSC sourcing for a particular application has yet to be achieved. For example, MSCs that activate their proteolytic environments may promote tissue remodeling, while those from different tissue sources may inhibit proteases and promote tissue stabilization. This study attempts to address these issues by analyzing MSCs isolated from three adult tissue sources in terms of their effects on their proteolytic microenvironments. Human bone marrow, adipose, and traumatized muscle derived MSCs were compared in their soluble and cellular-associated MMP components and activity. For all types of MSCs, MMP activity associated with the cell surface, but activity levels and MMP profiles differed with tissue source. All MSC types bound exogenous active MMPs at their surfaces. MSCs were also able to activate exogenous proMMP-2 and proMMP-13. This is in marked contrast to the MSC soluble compartment, which strongly inhibited MMPs via endogenous TIMPs. The exact TIMP used to inhibit the exogenous MMP differed with MSC type. Thus, MSCs saturate their environment with both MMPs and TIMPs. Since they bind and activate MMPs at their surfaces, the net result is a very controlled pericellular localization of MMP activities by MSCs. © 2013.

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

PubMed Central

Tweedy, Joshua; Spyrou, Maria Alexandra; Pearson, Max; Lassner, Dirk; Kuhl, Uwe; Gompels, Ursula A.

2016-01-01

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. PMID:26784220

Lodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome.

PubMed

Kesecioglu, J; Schultz, M J; Haitsma, J J; den Heeten, G J; Lachmann, B

2002-05-01

Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine x mL(-1)) or in 1:1 saline-iodixanol (160 mg iodine x mL(-1)), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH2O, lung volume at transpulmonary pressure of 5 cmH2O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH2O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.

Synthetic polymeric substrates as potent pro-oxidant versus anti-oxidant regulators of cytoskeletal remodeling and cell apoptosis.

PubMed

Sung, Hak-Joon; Chandra, Prafulla; Treiser, Matthew D; Liu, Er; Iovine, Carmine P; Moghe, Prabhas V; Kohn, Joachim

2009-03-01

The role of reactive oxygen species (ROS)-mediated cell signal transduction pathways emanating from engineered cell substrates remains unclear. To elucidate the role, polymers derived from the amino acid L-tyrosine were used as synthetic matrix substrates. Variations in their chemical properties were created by co-polymerizing hydrophobic L-tyrosine derivatives with uncharged hydrophilic poly(ethylene glycol) (PEG, Mw = 1,000 Da), and negatively charged desaminotyrosyl-tyrosine (DT). These substrates were characterized for their intrinsic ability to generate ROS, as well as their ability to elicit Saos-2 cell responses in terms of intracellular ROS production, actin remodeling, and apoptosis. PEG-containing substrates induced both exogenous and intracellular ROS production, whereas the charged substrates reduced production of both types, indicating a coupling of exogenous ROS generation and intracellular ROS production. Furthermore, PEG-mediated ROS induction caused nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase and an increase in caspase-3 activity, confirming a link with apoptosis. PEG-rich pro-oxidant substrates caused cytoskeletal actin remodeling through beta-actin cleavage by caspase-3 into fractins. The fractins co-localized to the mitochondria and reduced the mitochondrial membrane potential. The remnant cytosolic beta-actin was polymerized and condensed, events consistent with apoptotic cell shrinkage. The cytoskeletal remodeling was integral to the further augmentation of intracellular ROS production. Conversely, the anti-oxidant DT-containing charged substrates suppressed the entire cascade of apoptotic progression. We demonstrate that ROS activity serves an important role in "outside-in" signaling for cells grown on substrates: the ROS activity couples exogenous stress, driven by substrate composition, to changes in intracellular signaling. This signaling causes cell apoptosis, which is mediated by actin remodeling.

Protective effect of exogenous hydrogen sulfide on pulmonary artery endothelial cells by suppressing endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease.

PubMed

Ding, Hai-Bo; Liu, Kai-Xiong; Huang, Jie-Feng; Wu, Da-Wen; Chen, Jun-Ying; Chen, Qing-Shi

2018-06-13

Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder characterized by inflammation, representing a significant leading cause of chronic morbidity and mortality. Reports have implicated hydrogen sulfide (H 2 S) in both the pathology and treatment of COPD. The present study aimed to explore the effects involved with exogenous H 2 S on endoplasmic reticulum stress (ERS) and pulmonary artery endothelial cells (PAECs) in a rat model of COPD. Rat models of COPD were successfully established by means of passive smoke exposure and intratracheal injection with lipopolysaccharide (LPS). Pulmonary function tests were performed and histopathological changes were observed. The expression of ERS markers, glucose-regulated protein-78 (GRP78), and C/EBP homologous protein (CHOP) and caspase-12, associated with ERS-induced apoptosis, were determined by western blot and immunohistochemistry methods. TUNEL assay was applied to determine the apoptosis index (AI) in PAECs. Treatment with NaHS was followed by the exhibition of markedly increased forced expiratory volume over 0.3 s (FEV0.3)/forced vital capacity (FVC) and dynamic lung compliance as well as integral optical density (IOD), with decreased RI among COPD rats. Western blot analysis, immunohistochemistry and TUNEL assay results revealed there to be reduced expressions of GRP78, CHOP and caspase-12 in the lung tissues and AI of PAECs, post NaHS treatment. The key findings of the current study highlight ERS in COPD rats, as well as well as reduced apoptosis in PAECs in connection with exogenous H 2 S by suppressing ERS. Copyright © 2018. Published by Elsevier Masson SAS.

Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity.

PubMed

McCoy, Andrea J; Maurelli, Anthony T

2005-07-01

Recent characterization of chlamydial genes encoding functional peptidoglycan (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to synthesize PG yet biochemical evidence for the synthesis of PG has yet to be demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria. Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D-alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we undertook a genetics-based approach to demonstrate and characterize the D-Ala-D-Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC. The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was cloned and placed under the control of the arabinose-inducible ara promoter and transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing deletions of both the ddlA and ddlB genes. Viability of the E. coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide became dependent on the expression of the chlamydial murC-ddl thus demonstrating functional ligase activity. Domain mapping of the full-length fusion protein and site-directed mutagenesis of the MurC domain revealed that the structure of the full fusion protein but not MurC enzymatic activity was required for ligase activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala. Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity. In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D-Ala-D-Ala. Together, these findings further support our hypothesis that PG is synthesized by members of the Chlamydiaceae family and suggest that D-amino acids, specifically D-Ala, are present in chlamydial PG.

Flow cytometric sex sorting affects CD4 membrane distribution and binding of exogenous DNA on bovine sperm cells.

PubMed

Domingues, William Borges; da Silveira, Tony Leandro Rezende; Komninou, Eliza Rossi; Monte, Leonardo Garcia; Remião, Mariana Härter; Dellagostin, Odir Antônio; Corcini, Carine Dahl; Varela Junior, Antônio Sergio; Seixas, Fabiana Kömmling; Collares, Tiago; Campos, Vinicius Farias

2017-08-01

Bovine sex-sorted sperm have been commercialized and successfully used for the production of transgenic embryos of the desired sex through the sperm-mediated gene transfer (SMGT) technique. However, sex-sorted sperm show a reduced ability to internalize exogenous DNA. The interaction between sperm cells and the exogenous DNA has been reported in other species to be a CD4-like molecule-dependent process. The flow cytometry-based sex-sorting process subjects the spermatozoa to different stresses causing changes in the cell membrane. The aim of this study was to elucidate the relationship between the redistribution of CD4-like molecules and binding of exogenous DNA to sex-sorted bovine sperm. In the first set of experiments, the membrane phospholipid disorder and the redistribution of the CD4 were evaluated. The second set of experiments was conducted to investigate the effect of CD4 redistribution on the mechanism of binding of exogenous DNA to sperm cells and the efficiency of lipofection in sex-sorted bovine sperm. Sex-sorting procedure increased the membrane phospholipid disorder and induced the redistribution of CD4-like molecules. Both X-sorted and Y-sorted sperm had decreased DNA bound to membrane in comparison with the unsorted sperm; however, the binding of the exogenous DNA was significantly increased with the addition of liposomes. Moreover, we demonstrated that the number of sperm-bound exogenous DNA was decreased when these cells were preincubated with anti-bovine CD4 monoclonal antibody, supporting our hypothesis that CD4-like molecules indeed play a crucial role in the process of exogenous DNA/bovine sperm cells interaction.

DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression

PubMed Central

Barr, Alexis R.; Cooper, Samuel; Heldt, Frank S.; Butera, Francesca; Stoy, Henriette; Mansfeld, Jörg; Novák, Béla; Bakal, Chris

2017-01-01

Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases. High p21 levels mediate G1 arrest via CDK inhibition, yet lower levels have no impact on G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2 couple to degrade p21 prior to the G1/S transition. Mathematical modelling reveals that a bistable switch, created by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21 levels low, preventing premature S-phase exit upon DNA damage. Thus, we characterize how p21 regulates the proliferation-quiescence decision to maintain genomic stability. PMID:28317845

Real-Time PCR in faecal samples of Triatoma infestans obtained by xenodiagnosis: proposal for an exogenous internal control.

PubMed

Bravo, Nicolás; Muñoz, Catalina; Nazal, Nicolás; Saavedra, Miguel; Martínez, Gabriela; Araya, Eduardo; Apt, Werner; Zulantay, Inés

2012-03-26

The polymerase chain reaction (PCR) has proved to be a sensitive technique to detect Trypanosoma cruzi in the chronic phase of Chagas disease, which is characterized by low and fluctuating parasitemia. Another technique proposed for parasitological diagnosis in this phase of infection combines a microscopic search for motile trypomastigote forms in faecal samples (FS) obtained by xenodiagnosis (XD) with conventional PCR (XD-PCR). In this study we evaluate the use of human blood DNA as an exogenous internal control (EIC) for real time PCR (qPCR) combined with XD (XD-qPCR) using chromosome 12 (X12) detection. None of the FS-XD evaluated by qPCR amplified for X12. Nevertheless, all the EIC-FS-XD mixtures amplified for X12. We determined that X12 is useful as an EIC for XD-qPCR because we showed that the FS-XD does not contain human DNA after 30 or more days of XD incubation. This information is relevant for research on T. cruzi by XD-qPCR since it allows ruling out inhibition and false negative results due to DNA loss during the process of extraction and purification.

Utilization of 2,6-diaminopurine by Salmonella typhimurium.

PubMed Central

Garber, B B; Gots, J S

1980-01-01

The pathway for the utilization of 2,6-diaminopurine (DAP) as an exogenous purine source in Salmonella typhimurium was examined. In strains able to use DAP as a purine source, mutant derivatives lacking either purine nucleoside phosphorylase or adenosine deaminase activity lost the ability to do so. The implied pathway of DAP utilization was via its conversion to DAP ribonucleoside by purine nucleoside phosphorylase, followed by deamination to guanosine by adenosine deaminase. Guanosine can then enter the established purine salvage pathways. In the course of defining this pathway, purine auxotrophs able to utilize DAP as sole purine source were isolated and partially characterized. These mutants fell into several classes, including (i) strains that only required an exogenous source of guanine nucleotides (e.g., guaA and guaB strains); (ii) strains that had a purF genetic lesion (i.e., were defective in alpha-5-phosphoribosyl 1-pyrophosphate amidotransferase activity); and (iii) strains that had constitutive levels of purine nucleoside phosphorylase. Selection among purine auxotrophs blocked in the de novo synthesis of inosine 5'-monophosphate, for efficient growth on DAP as sole source of purine nucleotides, readily yielded mutants which were defective in the regulation of their deoxyribonucleoside-catabolizing enzymes (e.g., deoR mutants). PMID:6782081

Fungal community composition in soils subjected to long-term chemical fertilization is most influenced by the type of organic matter.

PubMed

Sun, Ruibo; Dsouza, Melissa; Gilbert, Jack A; Guo, Xisheng; Wang, Daozhong; Guo, Zhibin; Ni, Yingying; Chu, Haiyan

2016-12-01

Organic matter application is a widely used practice to increase soil carbon content and maintain soil fertility. However, little is known about the effect of different types of organic matter, or the input of exogenous species from these materials, on soil fungal communities. In this study, fungal community composition was characterized from soils amended with three types of organic matter over a 30-year fertilization experiment. Chemical fertilization significantly changed soil fungal community composition and structure, which was exacerbated by the addition of organic matter, with the direction of change influenced by the type of organic matter used. The addition of organic matter significantly increased soil fungal richness, with the greatest richness achieved in soils amended with pig manure. Importantly, following addition of cow and pig manure, fungal taxa associated with these materials could be found in the soil, suggesting that these exogenous species can augment soil fungal composition. Moreover, the addition of organic matter decreased the relative abundance of potential pathogenic fungi. Overall, these results indicate that organic matter addition influences the composition and structure of soil fungal communities in predictable ways. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Indole-3-acetic acid in Fusarium graminearum: Identification of biosynthetic pathways and characterization of physiological effects.

PubMed

Luo, Kun; Rocheleau, Hélène; Qi, Peng-Fei; Zheng, You-Liang; Zhao, Hui-Yan; Ouellet, Thérèse

2016-09-01

Fusarium graminearum is a devastating pathogenic fungus causing fusarium head blight (FHB) of wheat. This fungus can produce indole-3-acetic acid (IAA) and a very large amount of IAA accumulates in wheat head tissues during the first few days of infection by F. graminearum. Using liquid culture conditions, we have determined that F. graminearum can use tryptamine (TAM) and indole-3-acetonitrile (IAN) as biosynthetic intermediates to produce IAA. It is the first time that F. graminearum is shown to use the l-tryptophan-dependent TAM and IAN pathways rather than the indole-3-acetamide or indole-3-pyruvic acid pathways to produce IAA. Our experiments also showed that exogenous IAA was metabolized by F. graminearum. Exogenous IAA, TAM, and IAN inhibited mycelial growth; IAA and IAN also affected the hyphae branching pattern and delayed macroconidium germination. IAA and TAM had a small positive effect on the production of the mycotoxin 15-ADON while IAN inhibited its production. Our results showed that IAA and biosynthetic intermediates had a significant effect on F. graminearum physiology and suggested a new area of exploration for fungicidal compounds. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Exogenous and endogenous attention during perceptual learning differentially affect post-training target thresholds

PubMed Central

Mukai, Ikuko; Bahadur, Kandy; Kesavabhotla, Kartik; Ungerleider, Leslie G.

2012-01-01

There is conflicting evidence in the literature regarding the role played by attention in perceptual learning. To further examine this issue, we independently manipulated exogenous and endogenous attention and measured the rate of perceptual learning of oriented Gabor patches presented in different quadrants of the visual field. In this way, we could track learning at attended, divided-attended, and unattended locations. We also measured contrast thresholds of the Gabor patches before and after training. Our results showed that, for both exogenous and endogenous attention, accuracy in performing the orientation discrimination improved to a greater extent at attended than at unattended locations. Importantly, however, only exogenous attention resulted in improved contrast thresholds. These findings suggest that both exogenous and endogenous attention facilitate perceptual learning, but that these two types of attention may be mediated by different neural mechanisms. PMID:21282340

Alleviation of cadmium toxicity to Cole (Brassica campestris L. Cruciferae) by exogenous glutathione

NASA Astrophysics Data System (ADS)

Wang, Jun; Huang, Bin; Chen, Xin; Shi, Yi

2017-04-01

In this study, we determined the influence of exogenous GSH on cadmium toxicity to cole. GSH addition had beneficial effect on plant development and growth, especially on aboveground biomass and root length. Despite that exogenous GSH insignificantly promoted Cd uptake by the plant, it could decrease of Cd root-to-shoot transport and ameliorate Cd toxicity to the plant. At 6 mg Cd kg-1 soil, GSH addition well countered the Cd-induced significant reduction in CAT activity, but only insignificantly decreased MDA content, suggesting exogenous GSH might indirectly protect plant against oxidative stress via regulating antioxidative enzyme activities. However, at 12 mg Cd kg-1 soil, GSH application insignificantly increased the antioxidant activities but significantly decreased MDA content, indicating external GSH could directly participate in removing radical oxygen species. The results suggest exogenous GSH may have the potential of decreasing Cd accumulation in the edible parts of cultivars and alleviating Cd toxicity.

Current Concepts of Bruxism.

PubMed

Manfredini, Daniele; Serra-Negra, Junia; Carboncini, Fabio; Lobbezoo, Frank

Bruxism is a common phenomenon, and emerging evidence suggests that biologic, psychologic, and exogenous factors have greater involvement than morphologic factors in its etiology. Diagnosis should adopt the grading system of possible, probable, and definite. In children, it could be a warning sign of certain psychologic disorders. The proposed mechanism for the bruxism-pain relationship at the individual level is that stress sensitivity and anxious personality traits may be responsible for bruxism activities that may lead to temporomandibular pain, which in turn is modulated by psychosocial factors. A multiple-P (plates, pep talk, psychology, pills) approach involving reversible treatments is recommended, and adult prosthodontic management should be based on a common-sense cautionary approach.

Development and applications of transgenesis in the yellow fever mosquito, Aedes aegypti.

PubMed

Adelman, Zachary N; Jasinskiene, Nijole; James, Anthony A

2002-04-30

Transgenesis technology has been developed for the yellow fever mosquito, Aedes aegypti. Successful integration of exogenous DNA into the germline of this mosquito has been achieved with the class II transposable elements, Hermes, mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of Drosophila melanogaster, and fluorescent protein genes, can be used to monitor the insertion of these elements. The availability of multiple elements and marker genes provides a powerful set of tools to investigate basic biological properties of this vector insect, as well as the materials for developing novel, genetics-based, control strategies for the transmission of disease.

Nanoparticle Tracking Analysis for Determination of Hydrodynamic Diameter, Concentration, and Zeta-Potential of Polyplex Nanoparticles.

PubMed

Wilson, David R; Green, Jordan J

2017-01-01

Nanoparticle tracking analysis (NTA) is a recently developed nanoparticle characterization technique that offers certain advantages over dynamic light scattering for characterizing polyplex nanoparticles in particular. Dynamic light scattering results in intensity-weighted average measurements of nanoparticle characteristics. In contrast, NTA directly tracks individual particles, enabling concentration measurements as well as the direct determination of number-weighted particle size and zeta-potential. A direct number-weighted assessment of nanoparticle characteristics is particularly useful for polydisperse samples of particles, including many varieties of gene delivery particles that can be prone to aggregation. Here, we describe the synthesis of poly(beta-amino ester)/deoxyribonucleic acid (PBAE/DNA) polyplex nanoparticles and their characterization using NTA to determine hydrodynamic diameter, zeta-potential, and concentration. Additionally, we detail methods of labeling nucleic acids with fluorophores to assess only those polyplex nanoparticles containing plasmids via NTA. Polymeric gene delivery of exogenous plasmid DNA has great potential for treating a wide variety of diseases by inducing cells to express a gene of interest.

Nucleic-acid-programmed Ag-nanoclusters as a generic platform for visualization of latent fingerprints and exogenous substances.

PubMed

Ran, Xiang; Wang, Zhenzhen; Zhang, Zhijun; Pu, Fang; Ren, Jinsong; Qu, Xiaogang

2016-01-11

We display a nucleic acid controlled AgNC platform for latent fingerprint visualization. The versatile emission of aptamer-modified AgNCs was regulated by the nearby DNA regions. Multi-color images for simultaneous visualization of fingerprints and exogenous components were successfully obtained. A quantitative detection strategy for exogenous substances in fingerprints was also established.

Exogenous spatial attention influences figure-ground assignment.

PubMed

Vecera, Shaun P; Flevaris, Anastasia V; Filapek, Joseph C

2004-01-01

In a hierarchical stage account of vision, figure-ground assignment is thought to be completed before the operation of focal spatial attention. Results of previous studies have supported this account by showing that unpredictive, exogenous spatial precues do not influence figure-ground assignment, although voluntary attention can influence figure-ground assignment. However, in these studies, attention was not summoned directly to a region in a figure-ground display. In three experiments, we addressed the relationship between figure-ground assignment and visuospatial attention. In Experiment 1, we replicated the finding that exogenous precues do not influence figure-ground assignment when they direct attention outside of a figure-ground stimulus. In Experiment 2, we demonstrated that exogenous attention can influence figure-ground assignment if it is directed to one of the regions in a figure-ground stimulus. In Experiment 3, we demonstrated that exogenous attention can influence figure-ground assignment in displays that contain a Gestalt figure-ground cue; this result suggests that figure-ground processes are not entirely completed prior to the operation of focal spatial attention. Exogenous spatial attention acts as a cue for figure-ground assignment and can affect the outcome of figure-ground processes.

The effect of exogenous calcium on mitochondria, respiratory metabolism enzymes and ion transport in cucumber roots under hypoxia

PubMed Central

He, Lizhong; Li, Bin; Lu, Xiaomin; Yuan, Lingyun; Yang, Yanjuan; Yuan, Yinghui; Du, Jing; Guo, Shirong

2015-01-01

Hypoxia induces plant stress, particularly in cucumber plants under hydroponic culture. In plants, calcium is involved in stress signal transmission and growth. The ultimate goal of this study was to shed light on the mechanisms underlying the effects of exogenous calcium on the mitochondrial antioxidant system, the activity of respiratory metabolism enzymes, and ion transport in cucumber (Cucumis sativus L. cv. Jinchun No. 2) roots under hypoxic conditions. Our experiments revealed that exogenous calcium reduces the level of reactive oxygen species (ROS) and increases the activity of antioxidant enzymes in mitochondria under hypoxia. Exogenous calcium also enhances the accumulation of enzymes involved in glycolysis and the tricarboxylic acid (TCA) cycle. We utilized fluorescence and ultrastructural cytochemistry methods to observe that exogenous calcium increases the concentrations of Ca2+ and K+ in root cells by increasing the activity of plasma membrane (PM) H+-ATPase and tonoplast H+-ATPase and H+-PPase. Overall, our results suggest that hypoxic stress has an immediate and substantial effect on roots. Exogenous calcium improves metabolism and ion transport in cucumber roots, thereby increasing hypoxia tolerance in cucumber. PMID:26304855

Considerations on the Use of Exogenous Fibrolytic Enzymes to Improve Forage Utilization

PubMed Central

Mendoza, Germán D.; Plata-Pérez, Fernando X.

2014-01-01

Digestion of cell wall fractions of forage in the rumen is incomplete due to the complex links which limit their degradation. It is therefore necessary to find options to optimize the use of forages in ruminant production systems. One alternative is to use exogenous enzymes. Exogenous fibrolytic enzymes are of fungal or bacterial origin and increase nutrient availability from the cell wall, which consists of three fractions in different proportions depending on the species of forage: digestible, potentially digestible, and indigestible. The response to addition of exogenous enzymes varies with the type of forage; many researchers infer that there are enzyme-forage interactions but fail to explain the biological mechanism. We hypothesize that the response is related to the proportion of the potentially digestible fraction. The exogenous enzyme activity depends on several factors but if the general conditions for enzyme action are available, the potentially digestible fraction may determine the magnitude of the response. Results of experiments with exogenous fibrolytic enzymes in domestic ruminants are inconsistent. This, coupled with their high cost, has made their use unattractive to farmers. Development of cheaper products exploring other microorganisms with fibrolytic activity, such as Fomes fomentarius or Cellulomonas flavigena, is required. PMID:25379525

An Exogenous Surfactant-Producing Bacillus subtilis Facilitates Indigenous Microbial Enhanced Oil Recovery

PubMed Central

Gao, Peike; Li, Guoqiang; Li, Yanshu; Li, Yan; Tian, Huimei; Wang, Yansen; Zhou, Jiefang; Ma, Ting

2016-01-01

This study used an exogenous lipopeptide-producing Bacillus subtilis to strengthen the indigenous microbial enhanced oil recovery (IMEOR) process in a water-flooded reservoir in the laboratory. The microbial processes and driving mechanisms were investigated in terms of the changes in oil properties and the interplay between the exogenous B. subtilis and indigenous microbial populations. The exogenous B. subtilis is a lipopeptide producer, with a short growth cycle and no oil-degrading ability. The B. subtilis facilitates the IMEOR process through improving oil emulsification and accelerating microbial growth with oil as the carbon source. Microbial community studies using quantitative PCR and high-throughput sequencing revealed that the exogenous B. subtilis could live together with reservoir microbial populations, and did not exert an observable inhibitory effect on the indigenous microbial populations during nutrient stimulation. Core-flooding tests showed that the combined exogenous and indigenous microbial flooding increased oil displacement efficiency by 16.71%, compared with 7.59% in the control where only nutrients were added, demonstrating the application potential in enhanced oil recovery in water-flooded reservoirs, in particular, for reservoirs where IMEOR treatment cannot effectively improve oil recovery. PMID:26925051

An Exogenous Surfactant-Producing Bacillus subtilis Facilitates Indigenous Microbial Enhanced Oil Recovery.

PubMed

Gao, Peike; Li, Guoqiang; Li, Yanshu; Li, Yan; Tian, Huimei; Wang, Yansen; Zhou, Jiefang; Ma, Ting

2016-01-01

This study used an exogenous lipopeptide-producing Bacillus subtilis to strengthen the indigenous microbial enhanced oil recovery (IMEOR) process in a water-flooded reservoir in the laboratory. The microbial processes and driving mechanisms were investigated in terms of the changes in oil properties and the interplay between the exogenous B. subtilis and indigenous microbial populations. The exogenous B. subtilis is a lipopeptide producer, with a short growth cycle and no oil-degrading ability. The B. subtilis facilitates the IMEOR process through improving oil emulsification and accelerating microbial growth with oil as the carbon source. Microbial community studies using quantitative PCR and high-throughput sequencing revealed that the exogenous B. subtilis could live together with reservoir microbial populations, and did not exert an observable inhibitory effect on the indigenous microbial populations during nutrient stimulation. Core-flooding tests showed that the combined exogenous and indigenous microbial flooding increased oil displacement efficiency by 16.71%, compared with 7.59% in the control where only nutrients were added, demonstrating the application potential in enhanced oil recovery in water-flooded reservoirs, in particular, for reservoirs where IMEOR treatment cannot effectively improve oil recovery.

Expression, Purification and Characterization of Ricin vectors used for exogenous antigen delivery into the MHC Class I presentation pathway

PubMed Central

Marsden, Catherine J.; Lord, J. Michael; Roberts, Lynne M.

2003-01-01

Disarmed versions of the cytotoxin ricin can deliver fused peptides into target cells leading to MHC class I-restricted antigen presentation [Smith et al. J Immunol 2002; 169:99-107]. The ricin delivery vector must contain an attenuated catalytic domain to prevent target cell death, and the fused peptide epitope must remain intact for delivery and functional loading to MHC class I molecules. Expression in E. coli and purification by cation exchange chromatography of the fusion protein is described. Before used for delivery, the activity of the vector must be characterized in vitro, via an N-glycosidase assay, and in vivo, by a cytotoxicity assay. The presence of an intact epitope must be confirmed using mass spectrometry by comparing the actual mass with the predicted mass. PMID:12734560

[Grain Size Distribution Characteristics of Suspended Particulate Matter as Influenced by the Apparent Pollution in the Eutrophic Urban Landscape Water Body].

PubMed

Gong, Dan-yan; Pan, Yang; Huang, Yong; Bao, Wei; Li, Qian-qian

2016-03-15

Grain size distribution characteristics of suspended particulate matter (SPM) reflects the apparent polluted condition of the urban landscape water. In order to explore the internal relationship between the eutrophication of urban landscape water's apparent pollution and grain size distribution of SPM, and its influencing factors, this paper selected five representative sampling sites in Feng Jin River which is a typical eutrophication river in Suzhou City, measured the grain size distribution of SPM, sensation pollution index (SPI) and water quality index, and analyzed their correlation. The results showed that: The rich nutrient water possessed a similar characteristics in grain size distribution. The grain size distribution of SPM in water was multimodal, and the the peak position was roughly the same; the grain size distribution of SPM was composed by multiple components. It could be roughly divided into six parts with the particle size range of every group being < 1.5 µm, 1.5-8 µm, 8-35 µm, 35-186 µm, 186-516 µm, > 516 µm. The component III was superior (with an average volume fraction of 38.3%-43.2%), and its volume fraction had a significant positive relation with the SPI value and the Chl-a content. The increase of component III volume fraction was the reflection of particle size's result of increasing SPI value. The increase of component III volume fraction was mainly derived from the increasing algal content. The volume fraction of group IV + group VI + group V was significantly higher under the condition of exogenous enter. When there was no exogenous component, the volume fraction of group IV + group VI + group V had a significant negative correlation with SPI value; when there were exogenous components, the volume fraction of group IV + group VI + group V had a weak positive correlation with SPI value, but the correlation did not reach a significant level. Environmental factors (Fv/Fm and DO) and exogenous factors had an influence by functioning on the algal content which signified the polluted material, and then affected the volume fraction of particle size's components and the quality of apparent water. Hydrodynamic conditions mainly had a certain influence on the median particle size, and had no effect on the apparent polluted condition of water.

Generation and characterization of human iPSC line generated from mesenchymal stem cells derived from adipose tissue.

PubMed

Zapata-Linares, Natalia; Rodriguez, Saray; Mazo, Manuel; Abizanda, Gloria; Andreu, Enrique J; Barajas, Miguel; Prosper, Felipe; Rodriguez-Madoz, Juan R

2016-01-01

In this work, mesenchymal stem cells derived from adipose tissue (ADSCs) were used for the generation of the human-induced pluripotent stem cell line G15.AO. Cell reprogramming was performed using retroviral vectors containing the Yamanaka factors, and the generated G15.AO hiPSC line showed normal karyotype, silencing of the exogenous reprogramming factors, induction of the typical pluripotency-associated markers, alkaline phosphatase enzymatic activity, and in vivo and in vitro differentiation ability to the three germ layers. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Fast deep-tissue multispectral optoacoustic tomography (MSOT) for preclinical imaging of cancer and cardiovascular disease

NASA Astrophysics Data System (ADS)

Taruttis, Adrian; Razansky, Daniel; Ntziachristos, Vasilis

2012-02-01

Optoacoustic imaging has enabled the visualization of optical contrast at high resolutions in deep tissue. Our Multispectral optoacoustic tomography (MSOT) imaging results reveal internal tissue heterogeneity, where the underlying distribution of specific endogenous and exogenous sources of absorption can be resolved in detail. Technical advances in cardiac imaging allow motion-resolved multispectral measurements of the heart, opening the way for studies of cardiovascular disease. We further demonstrate the fast characterization of the pharmacokinetic profiles of lightabsorbing agents. Overall, our MSOT findings indicate new possibilities in high resolution imaging of functional and molecular parameters.

Melatonin enhances cold tolerance in drought-primed wild-type and abscisic acid-deficient mutant barley.

PubMed

Li, Xiangnan; Tan, Dun-Xian; Jiang, Dong; Liu, Fulai

2016-10-01

Melatonin is involved in multiple plant developmental processes and various stress responses. To explore the roles of melatonin played as well as its association with abscisic acid (ABA) in a process of drought priming-induced cold tolerance (DPICT), a wild-type barley and its ABA-deficient mutant Az34 counterpart were selected for comparison, in which the effects of melatonin application (either foliarly or rhizospherically) and/or drought priming on the cold tolerance of both types of barleys were systematically investigated. It was demonstrated that the early drought priming induced an increase of endogenous melatonin production, which is not ABA dependent. In addition, exogenously applied melatonin resulted in higher ABA concentration in the drought-primed plants than in the nonprimed plants when exposed to cold stress, indicating that ABA responded in a drought-dependent manner. The interplay of melatonin and ABA leads to plants maintaining better water status. Drought priming-induced melatonin accumulation enhanced the antioxidant capacity in both chloroplasts and mitochondria, which sustained the photosynthetic electron transport in photosynthetic apparatus of the plants under cold stress. These results suggest that the exogenous melatonin application enhances the DPICT by modulating subcellular antioxidant systems and ABA levels in barley. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs.

PubMed

Jaén, Maria Luisa; Vilà, Laia; Elias, Ivet; Jimenez, Veronica; Rodó, Jordi; Maggioni, Luca; Ruiz-de Gopegui, Rafael; Garcia, Miguel; Muñoz, Sergio; Callejas, David; Ayuso, Eduard; Ferré, Tura; Grifoll, Iris; Andaluz, Anna; Ruberte, Jesus; Haurigot, Virginia; Bosch, Fatima

2017-09-15

Diabetes is a complex metabolic disease that exposes patients to the deleterious effects of hyperglycemia on various organs. Achievement of normoglycemia with exogenous insulin treatment requires the use of high doses of hormone, which increases the risk of life-threatening hypoglycemic episodes. We developed a gene therapy approach to control diabetic hyperglycemia based on co-expression of the insulin and glucokinase genes in skeletal muscle. Previous studies proved the feasibility of gene delivery to large diabetic animals with adeno-associated viral (AAV) vectors. Here, we report the long-term (∼8 years) follow-up after a single administration of therapeutic vectors to diabetic dogs. Successful, multi-year control of glycemia was achieved without the need of supplementation with exogenous insulin. Metabolic correction was demonstrated through normalization of serum levels of fructosamine, triglycerides, and cholesterol and remarkable improvement in the response to an oral glucose challenge. The persistence of vector genomes and therapeutic transgene expression years after vector delivery was documented in multiple samples from treated muscles, which showed normal morphology. Thus, this study demonstrates the long-term efficacy and safety of insulin and glucokinase gene transfer in large animals and especially the ability of the system to respond to the changes in metabolic needs as animals grow older.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

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

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Transgenic Studies on the Involvement of Cytokinin and Gibberellin in Male Development

PubMed Central

Huang, Shihshieh; Cerny, R. Eric; Qi, Youlin; Bhat, Deepti; Aydt, Carrie M.; Hanson, Doris D.; Malloy, Kathleen P.; Ness, Linda A.

2003-01-01

Numerous plant hormones interact during plant growth and development. Elucidating the role of these various hormones on particular tissue types or developmental stages has been difficult with exogenous applications or constitutive expression studies. Therefore, we used tissue-specific promoters expressing CKX1 and gai, genes involved in oxidative cytokinin degradation and gibberellin (GA) signal transduction, respectively, to study the roles of cytokinin and GA in male organ development. Accumulation of CKX1 in reproductive tissues of transgenic maize (Zea mays) resulted in male-sterile plants. The male development of these plants was restored by applications of kinetin and thidiazuron. Similarly, expression of gai specifically in anthers and pollen of tobacco (Nicotiana tabacum) and Arabidopsis resulted in the abortion of these respective tissues. The gai-induced male-sterile phenotype exhibited by the transgenic plants was reversible by exogenous applications of kinetin. Our results provide molecular evidence of the involvement of cytokinin and GA in male development and support the hypothesis that the male development is controlled in concert by multiple hormones. These studies also suggest a potential method for generating maintainable male sterility in plants by using existing agrochemicals that would reduce the expense of seed production for existing hybrid crops and provide a method to produce hybrid varieties of traditionally non-hybrid crops. PMID:12644677

Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe.

PubMed

Minc, Nicolas; Chang, Fred

2010-04-27

Electric signals surround tissues and cells and have been proposed to participate in directing cell polarity in processes such as development, wound healing, and host invasion [1, 2]. The application of exogenous electric fields (EFs) can direct cell polarization in cell types ranging from bacteria and fungi to neurons and neutrophils [3-7]. The mechanisms by which EFs modulate cell polarity, however, remain poorly understood. Here we introduce the fission yeast Schizosaccharomyces pombe as a model organism to elucidate the mechanisms underlying this process. In these rod-shaped cells, an exogenous EF reorients cell growth in a direction orthogonal to the field, producing cells with a bent morphology. A candidate genetic screen identifies conserved factors involved in this process: an integral membrane proton ATPase pma1p that regulates intracellular pH, the small GTPase cdc42p, and the formin for3p that assembles actin cables. Interestingly, mutants in these genes still respond to the EF but orient in a different direction, toward the anode. In addition, EFs also cause electrophoretic movement of cell wall synthase complex proteins toward the anode. These data suggest molecular models for how the EF reorients cell polarization by modulating intracellular pH and steering cell polarity factors in multiple directions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR.

PubMed

Jakočiūnas, Tadas; Jensen, Emil D; Jensen, Michael K; Keasling, Jay D

2018-01-01

Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. CasEMBLR capitalizes on the CRISPR/Cas9 technology to generate double-strand breaks in genomic loci, thus prompting native homologous recombination (HR) machinery to integrate exogenously derived homology templates. As proof-of-principle for microbial cell factory development, CasEMBLR was used for one-step assembly and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking out two genes. This new method complements and improves the field of genome engineering in S. cerevisiae by providing a more flexible platform for rapid and precise strain building.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya

DOE PAGES

Hilker, Frank M.; Allen, Linda J. S.; Bokil, Vrushali A.; ...

2017-08-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with largemore » holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Finally, our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.« less

Real-world volatile organic compound emission rates from seated adults and children for use in indoor air studies.

PubMed

Stönner, C; Edtbauer, A; Williams, J

2018-01-01

Human beings emit many volatile organic compounds (VOCs) of both endogenous (internally produced) and exogenous (external source) origin. Here we present real-world emission rates of volatile organic compounds from cinema audiences (50-230 people) as a function of time in multiple screenings of three films. The cinema location and film selection allowed high-frequency measurement of human-emitted VOCs within a room flushed at a known rate so that emissions rates could be calculated for both adults and children. Gas-phase emission rates are analyzed as a function of time of day, variability during the film, and age of viewer. The average emission rates of CO 2 , acetone, and isoprene were lower (by a factor of ~1.2-1.4) for children under twelve compared to adults while for acetaldehyde emission rates were equivalent. Molecules influenced by exogenous sources such as decamethylcyclopentasiloxanes and methanol tended to decrease over the course of day and then rise for late evening screenings. These results represent average emission rates of people under real-world conditions and can be used in indoor air quality assessments and building design. Averaging over a large number of people generates emission rates that are less susceptible to individual behaviors. © 2017 The Authors. Indoor Air published by John Wiley & Sons Ltd.

Investigations into the differential reactivity of endogenous and exogenous mercury species in coastal sediments.

PubMed

Bouchet, S; Rodriguez-Gonzalez, P; Bridou, R; Monperrus, M; Tessier, E; Anschutz, P; Guyoneaud, R; Amouroux, D

2013-03-01

Stable isotopic tracer methodologies now allow the evaluation of the reactivity of the endogenous (ambient) and exogenous (added) Hg to further predict the potential effect of Hg inputs in ecosystems. The differential reactivity of endogenous and exogenous Hg was compared in superficial sediments collected in a coastal lagoon (Arcachon Bay) and in an estuary (Adour River) from the Bay of Biscay (SW France). All Hg species (gaseous, aqueous, and solid fraction) and ancillary data were measured during time course slurry experiments under variable redox conditions. The average endogenous methylation yield was higher in the estuarine (1.2 %) than in the lagoonal sediment (0.5 %), although both methylation and demethylation rates were higher in the lagoonal sediment in relation with a higher sulfate-reducing activity. Demethylation was overall more consistent than methylation in both sediments. The endogenous and exogenous Hg behaviors were always correlated but the exogenous inorganic Hg (IHg) partitioning into water was 2.0-4.3 times higher than the endogenous one. Its methylation was just slightly higher (1.4) in the estuarine sediment while the difference in the lagoonal sediment was much larger (3.6). The relative endogenous and exogenous methylation yields were not correlated to IHg partitioning, demonstrating that the bioavailable species distributions were different for the two IHg pools. In both sediments, the exogenous IHg partitioning equaled the endogenous one within a week, while its higher methylation lasted for months. Such results provide an original assessment approach to compare coastal sediment response to Hg inputs.

Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor.

PubMed

Xian, Hua; Xian, Yun; Liu, Lili; Wang, Yongjun; He, Jianghong; Huang, Jianfei

2015-04-01

With the exception of standard inguinal orchidopexy, treatment of cryptorchidism with human chorionic gonadotropin has been performed for several years; however, its side effects have limited its application. The β‑nerve growth factor (NGF) and homeobox A10 (HoxA10) genes are closely associated with the development of the testes. To the best of our knowledge, whether exogenous NGF alters the endogenous levels of NGF and HoxA10 in cryptorchidism in rats remains to be elucidated. The aim of the present study was to evaluate the gene and protein expression of NGF and HoxA10 in experimental cryptorchidism following treatment with exogenous NGF. A unilateral mechanical cryptorchidism model in Sprague-Dawley rats was established and different concentrations of exogenous NGF were administered to observe the effects of NGF on cryptorchidism. Changes in the gene and protein expression levels of NGF and HoxA10 in the cryptorchid tissues of each group were identified using one step reverse transcription-quantitative polymerase chain reaction, in situ hybridization with digoxigenin‑labeled‑β‑NGF RNA probes, immunofluorescence and immunohistochemistry, respectively. The expression levels of NGF and HoxA10 were markedly higher in the group treated with a high dose of exogenous NGF compared with the group treated with a low dose of exogenous NGF and the group treated with human chorionic gonadotropin. These results confirmed the potential therapeutic effect of exogenous NGF in human cryptorchidism.

Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function.

PubMed

Molineaux, Anna C; Maier, Jennifer A; Schecker, Teresa; Sears, Karen E

2015-03-01

Retinoic acid (RA) is a vitamin A derivative. Exposure to exogenous RA generates congenital limb malformations (CLMs) in species from frogs to humans. These CLMs include but are not limited to oligodactyly and long-bone hypoplasia. The processes by which exogenous RA induces CLMs in mammals have been best studied in mouse, but as of yet remain unresolved. We investigated the impact of exogenous RA on the cellular and molecular development of the limbs of a nonrodent model mammal, the opossum Monodelphis domestica. Opossums exposed to exogenous retinoic acid display CLMs including oligodactly, and results are consistent with opossum development being more susceptible to RA-induced disruptions than mouse development. Exposure of developing opossums to exogenous RA leads to an increase in cell death in the limb mesenchyme that is most pronounced in the zone of polarizing activity, and a reduction in cell proliferation throughout the limb mesenchyme. Exogenous RA also disrupts the expression of Shh in the zone of polarizing activity, and Fgf8 in the apical ectodermal ridge, and other genes with roles in the regulation of limb development and cell death. Results are consistent with RA inducing CLMs in opossum limbs by disrupting the functions of the apical ectodermal ridge and zone of polarizing activity, and driving an increase in cell death and reduction of cell proliferation in the mesenchyme of the developing limb. © 2015 Wiley Periodicals, Inc.

Measurement of Endogenous versus Exogenous Formaldehyde-Induced DNA-Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry.

PubMed

Lai, Yongquan; Yu, Rui; Hartwell, Hadley J; Moeller, Benjamin C; Bodnar, Wanda M; Swenberg, James A

2016-05-01

DNA-protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([(13)CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous ((13)CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues but were absent in tissues distant to the site of contact. This observation, together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined, suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for the persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde and may inform improved disease prevention and treatment strategies. Cancer Res; 76(9); 2652-61. ©2016 AACR. ©2016 American Association for Cancer Research.

Exogenous spermidine is enhancing tomato tolerance to salinity-alkalinity stress by regulating chloroplast antioxidant system and chlorophyll metabolism.

PubMed

Li, Jianming; Hu, Lipan; Zhang, Li; Pan, Xiongbo; Hu, Xiaohui

2015-12-29

Salinity-alkalinity stress is known to adversely affect a variety of processes in plants, thus inhibiting growth and decreasing crop yield. Polyamines protect plants against a variety of environmental stresses. However, whether exogenous spermidine increases the tolerance of tomato seedlings via effects on chloroplast antioxidant enzymes and chlorophyll metabolism is unknown. In this study, we examined the effect of exogenous spermidine on chlorophyll synthesis and degradation pathway intermediates and related enzyme activities, as well as chloroplast ultrastructure, gene expression, and antioxidants in salinity-alkalinity-stressed tomato seedlings. Salinity-alkalinity stress disrupted chlorophyll metabolism and hindered uroorphyrinogen III conversion to protoporphyrin IX. These effects were more pronounced in seedlings of cultivar Zhongza No. 9 than cultivar Jinpengchaoguan. Under salinity-alkalinity stress, exogenous spermidine alleviated decreases in the contents of total chlorophyll and chlorophyll a and b in seedlings of both cultivars following 4 days of stress. With extended stress, exogenous spermidine reduced the accumulation of δ-aminolevulinic acid, porphobilinogen, and uroorphyrinogen III and increased the levels of protoporphyrin IX, Mg-protoporphyrin IX, and protochlorophyllide, suggesting that spermidine promotes the conversion of uroorphyrinogen III to protoporphyrin IX. The effect occurred earlier in cultivar Jinpengchaoguan than in cultivar Zhongza No. 9. Exogenous spermidine also alleviated the stress-induced increases in malondialdehyde content, superoxide radical generation rate, chlorophyllase activity, and expression of the chlorophyllase gene and the stress-induced decreases in the activities of antioxidant enzymes, antioxidants, and expression of the porphobilinogen deaminase gene. In addition, exogenous spermidine stabilized the chloroplast ultrastructure in stressed tomato seedlings. The tomato cultivars examined exhibited different capacities for responding to salinity-alkalinity stress. Exogenous spermidine triggers effective protection against damage induced by salinity-alkalinity stress in tomato seedlings, probably by maintaining chloroplast structural integrity and alleviating salinity-alkalinity-induced oxidative damage, most likely through regulation of chlorophyll metabolism and the enzymatic and non-enzymatic antioxidant systems in chloroplast. Exogenous spermidine also exerts positive effects at the transcription level, such as down-regulation of the expression of the chlorophyllase gene and up-regulation of the expression of the porphobilinogen deaminase gene.

Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1.

PubMed

Xu, Jiaqi; Sadahira, Takuya; Kinoshita, Rie; Li, Shun-Ai; Huang, Peng; Wada, Koichiro; Araki, Motoo; Ochiai, Kazuhiko; Noguchi, Hirofumi; Sakaguchi, Masakiyo; Nasu, Yasutomo; Watanabe, Masami

2017-11-01

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)β-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-β-catenin (activated form of β-catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/β-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/β-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/β-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/β-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-β-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-β-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-β-catenin and inhibits Wnt/β-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/β-catenin signaling.

Permethrin induction of multiple cytochrome P450 genes in insecticide resistant mosquitoes, Culex quinquefasciatus.

PubMed

Gong, Youhui; Li, Ting; Zhang, Lee; Gao, Xiwu; Liu, Nannan

2013-01-01

The expression of some insect P450 genes can be induced by both exogenous and endogenous compounds and there is evidence to suggest that multiple constitutively overexpressed P450 genes are co-responsible for the development of resistance to permethrin in resistant mosquitoes. This study characterized the permethrin induction profiles of P450 genes known to be constitutively overexpressed in resistant mosquitoes, Culex quinquefasciatus. The gene expression in 7 of the 19 P450 genes CYP325K3v1, CYP4D42v2, CYP9J45, (CYP) CPIJ000926, CYP325G4, CYP4C38, CYP4H40 in the HAmCqG8 strain, increased more than 2-fold after exposure to permethrin at an LC50 concentration (10 ppm) compared to their acetone treated counterpart; no significant differences in the expression of these P450 genes in susceptible S-Lab mosquitoes were observed after permethrin treatment. Eleven of the fourteen P450 genes overexpressed in the MAmCqG6 strain, CYP9M10, CYP6Z12, CYP9J33, CYP9J43, CYP9J34, CYP306A1, CYP6Z15, CYP9J45, CYPPAL1, CYP4C52v1, CYP9J39, were also induced more than doubled after exposure to an LC50 (0.7 ppm) dose of permethrin. No significant induction in P450 gene expression was observed in the susceptible S-Lab mosquitoes after permethrin treatment except for CYP6Z15 and CYP9J39, suggesting that permethrin induction of these two P450 genes are common to both susceptible and resistant mosquitoes while the induction of the others are specific to insecticide resistant mosquitoes. These results demonstrate that multiple P450 genes are co-up-regulated in insecticide resistant mosquitoes through both constitutive overexpression and induction mechanisms, providing additional support for their involvement in the detoxification of insecticides and the development of insecticide resistance.

Effect of Exogenous Abscisic Acid and Methyl Jasmonate on Anthocyanin Composition, Fatty Acids, and Volatile Compounds of Cabernet Sauvignon (Vitis vinifera L.) Grape Berries.

PubMed

Ju, Yan-Lun; Liu, Min; Zhao, Hui; Meng, Jiang-Fei; Fang, Yu-Lin

2016-10-12

The anthocyanin composition, fatty acids, and volatile aromas are important for Cabernet Sauvignon grape quality. This study evaluated the effect of exogenous abscisic acid (ABA) and methyl jasmonate (MeJA) on the anthocyanin composition, fatty acids, lipoxygenase activity, and the volatile compounds of Cabernet Sauvignon grape berries. Exogenous ABA and MeJA improved the content of total anthocyanins (TAC) and individual anthocyanins. Lipoxygenase (LOX) activity also increased after treatment. Furthermore, 16 fatty acids were detected. The linoleic acid concentration gradually increased with ABA concentration. The fatty acid content decreased with increasing MeJA concentration and then increased again, with the exception of linoleic acid. After exogenous ABA and MeJA treatment, the C6 aroma content increased significantly. Interestingly, the exogenous ABA and MeJA treatments improved mainly the content of 1-hexanol, hexanal, and 2-heptanol. These results provide insight into the effect of plant hormones on wine grapes, which is useful for grape quality improvement.

Effects of exogenous salinity (NaCl) gradient on Cd release in acidified contaminated brown soil

NASA Astrophysics Data System (ADS)

Zhang, Lina; Rong, Yong; Mao, Li; Gao, Zhiyuan; Liu, Xiaoyu; Dong, Zhicheng

2018-02-01

Taking acidified Cd contaminated brown soil in Yantai as the research object, based on different exogenous salinity (NaCl) gradient (0%, 0.3%, 0.6%, 0.9%, 1.5%, 2% and 5%), indoor simulation experiments of Cd release were carried out after field investigation. Results showed that there was a significantly positive relation (r>0.90) between Cd release concentration/amount/ratio and exogenous salt (NaCl). Besides, the more exogenous salt (NaCl) was added; maximum release concentration/amount of Cd appeared the earlier. It was found that exogenous salt (NaCl) addition could obviously promote Cd release from acidified Cd contaminated brown soil. It was believed that this could be mainly due to the cation exchange between Cd2+ and Na+, together with the dissociation and/or complexation between Cl- and Cd2+. In addition, available adsorption sites reduction by exchange base in soil causing Cd changed from solid state to soil solution was also a probable reason.

Transurethral lithotripsy with holmium-YAG laser of a large exogenous prostatic calculus.

PubMed

Hasegawa, Masanori; Ohara, Rei; Kanao, Kent; Nakajima, Yosuke

2011-04-01

Prostatic calculi are classified into two types, endogenous and exogenous calculi, based on their origin. Endogenous calculi are commonly observed in elderly men; however, exogenous prostatic calculi are extremely rare. We report here the case of a 51-year-old man who suffered incontinence and pollakiuria with a giant exogenous prostatic calculus almost completely replacing the prostatic tissue. X-rays and computed tomography demonstrated a large calculus of 65 × 58 mm in the small pelvic cavity. The patient underwent a transurethral lithotripsy with a holmium-YAG laser and a total of 85 g of disintegrated stones was retrieved and chemical stone analysis revealed the presence of magnesium ammonium phosphate. The incontinence improved and the voiding volume increased dramatically, and no stone recurrence in the prostatic fossa occurred at the 2 years follow-up. The etiology of this stone formation seemed to be based on some exogenous pathways combined with urinary stasis and chronic urinary infection due to compression fracture of the lumbar vertebra.

Saccade preparation is required for exogenous attention but not endogenous attention or IOR.

PubMed

Smith, Daniel T; Schenk, Thomas; Rorden, Chris

2012-12-01

Covert attention is tightly coupled with the control of eye movements, but there is controversy about how tight this coupling is. The premotor theory of attention proposes that activation of the eye movement system is necessary to produce shifts of attention. In this study, we experimentally prevented healthy participants from planning or executing eye movements and observed the effect on exogenous attention, inhibition of return (IOR), and endogenous attention. The participants experienced a deficit of exogenous attentional facilitation that was specific to locations that were inaccessible by saccade. In contrast, their ability to endogenously orient attention was preserved, as was IOR. These results show that (a) exogenous attention depends on motor preparation, (b) IOR is independent of motor preparation and exogenous attention, and (c) endogenous attention is independent of motor preparation. Although these data are consistent with a weak version of the premotor theory, we believe they can be better explained by a biased competition account of visual attention.

Do endogenous and exogenous action control compete for perception?

PubMed

Pfister, Roland; Heinemann, Alexander; Kiesel, Andrea; Thomaschke, Roland; Janczyk, Markus

2012-04-01

Human actions are guided either by endogenous action plans or by external stimuli in the environment. These two types of action control seem to be mediated by neurophysiologically and functionally distinct systems that interfere if an endogenously planned action suddenly has to be performed in response to an exogenous stimulus. In this case, the endogenous representation has to be deactivated first to give way to the exogenous system. Here we show that interference of endogenous and exogenous action control is not limited to motor-related aspects but also affects the perception of action-related stimuli. Participants associated two actions with contingent sensory effects in learning blocks. In subsequent test blocks, preparing one of these actions specifically impaired responding to the associated effect in an exogenous speeded detection task, yielding a blindness-like effect for arbitrary, learned action effects. In accordance with the theory of event coding, this finding suggests that action planning influences perception even in the absence of any physical similarities between action and to-be-perceived stimuli.

Evaluation of the efficacy of laparoscopic resection for the management of exogenous cesarean scar pregnancy.

PubMed

Wang, Guangwei; Liu, Xiaofei; Bi, Fangfang; Yin, Lili; Sa, Rina; Wang, Dandan; Yang, Qing

2014-05-01

To retrospectively analyze the clinical data of 71 patients with exogenous cesarean scar pregnancy (CSP) treated in our hospital in the past 2 years, to compare the outcomes of exogenous CSP treated with different methods, and to evaluate the safety and feasibility of laparoscopic resection of exogenous CSP. Comparative observational study. Tertiary medical centers. 71 women with exogenous cesarean scar pregnancy. Hysteroscopic resection of CSP, and laparoscopic resection of CSP. Operation time, intraoperative blood loss, postoperative drainage of the uterine cavity, postoperative days in hospital, time for β-human chorionic gonadotropin (β-hCG) to return to normal levels, absorption time of the mass. For the laparoscopic group, the time for serum β-hCG to return normal levels and the postoperative drainage of the uterine cavity were significantly lower than in the patients who had undergone hysteroscopic resection. We found no statistically significant difference in the intraoperative blood loss and postoperative days in hospital between the two groups, but the operation time was longer in laparoscopic group. Laparoscopic surgery for a cesarean scar pregnancy has the advantages of a high success rate, fewer complications, and a shorter time for β-hCG levels to normalize. This procedure is especially suitable for the treatment of exogenous CSP. Copyright © 2014. Published by Elsevier Inc.

[Effects of exogenous spermidine on Cucumis sativus L. seedlings photosynthesis under root zone hypoxia stress].

PubMed

Wang, Tian; Wang, Suping; Guo, Shirong; Sun, Yanjun

2006-09-01

With water culture, this paper studied the effects of exogenous spermidine (Spd) on the net photosynthetic rate (Pn), intercellular CO2 concentrations (Ci), stomatal conductance (Gs), transpiration rate (Tr), apparent quantum yield (phi c), and carboxylation efficiency (CE) of cucumber seedlings tinder hypoxia stress. The results showed that the Pn decreased gradually under hypoxia stress, and reached the minimum 10 days after by 63. 33% of the control. Compared with that of hypoxia-stressed plants, the Pn after 10 days application of exogenous Spd increased 1.25 times. A negative correlation (R2 = 0.4730 - 0.7118) was found between Pn and Ci. Gs and Tr changed in wider ranges, which decreased under hypoxia-stress, but increased under hypoxia-stress plus exogenous Spd application. There was a significant positive correlation between Gs and Tr (R2 = 0.7821 - 0.9458), but these two parameters had no significant correlation with Pn; Hypoxia stress induced a decrease of phi c and CE by 63.01% and 72.33%, respectively, while hypoxia stress plus exogenous Spd application made phi c and CE increase by 23% and 14%, respectively. The photo-inhibition of cucumber seedlings under hypoxia stress was mainly caused by non-stomatal limitation, while exogenous Spd alleviated the hypoxia stress by repairing photosynthesis system.

Role of Exogenous Progesterone in the Treatment of Men and Women with Substance Use Disorders: A Narrative Review.

PubMed

Peltier, MacKenzie R; Sofuoglu, Mehmet

2018-05-14

Substance use disorders (SUDs) remain problematic as many individuals are untreated or do not benefit from the currently available interventions. Thus, there is an urgent need to develop novel pharmacological interventions to treat SUDs. Evidence suggests that the female sex hormone, progesterone, attenuates the craving for and the euphoric effects of drugs of abuse. Research to date has demonstrated that progesterone may modulate responses to drugs of abuse and may have utility as a novel treatment for SUDs. A literature search was conducted to identify and examine studies that administered exogenous progesterone. Sixteen publications were identified, exploring the utility of exogenous progesterone or its metabolite, allopregnanolone, among a range of substances, including amphetamines (one study), benzodiazepines (one study), cocaine (nine studies), and tobacco/nicotine (five studies). Results indicated that exogenous progesterone and, its metabolite allopregnanolone, demonstrated preliminary efficacy as a treatment for substance use in both men and women. Notably, progesterone appears to target negative affect and augment cognitive functioning, especially among female substance users. Additional research is needed to explore the potential use of exogenous progesterone and allopregnanolone in the treatment of SUDs, including that associated with alcohol and opioids, but considering the current promising findings, exogenous progesterone and allopregnanolone may have utility as novel pharmacological treatments for SUDs.

BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy

PubMed Central

Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

2015-01-01

Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell’s response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF+ DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells. PMID:25991860

Dance partner or dance floor?: exogenous factors resulting in accidents in professional dancers.

PubMed

Wanke, Eileen M; Mill, Helmgard; Wanke, Alice; Davenport, Jaqueline; Checcetti, Fistd; Koch, Franziska; Groneberg, David A

2013-09-01

Injury prevention in professional dancers is very important due to the high risk for acute injuries posing a threat to dancers' careers. Causative factors of acute injuries in professional dance can be divided into exogenous and endogenous factors. Although both are known in professional dance, there is still a lack of data to have a differentiated view. The aim of this study is to analyze exogenous factors resulting in work accidents of professional dancers. The data for the evaluation were obtained from work accident reports (n = 1,438, female 722, male 716) from six Berlin Theatres. Evaluation and descriptive statistics were conducted by SPSS 18 and Excel 2007. About half (48.5%, n = 698) of all work accidents are caused by exogenous factors. The "dance partner" is the most common exogenous factor (39.9%), followed by the dance floor (28.24%) and props (13.6%). The lower extremity is the most frequent structure injured in either sex (male 47.3%, female 61.3%), followed by the upper extremity in females (14.6%) and spine in male dancers (19.8%). The stage is the most common injury location in both genders (males 63.9%, females 56.8%). Acute injuries caused by exogenous factors were particularly sustained during performances (males 58.8%, females 50.5%) and during rehearsals (males 33%, females 39.9%). This study shows the key significance of exogenous factors in acute injuries in professional dance. Preserving the dancers' health and preventing injuries takes top priority, and therefore, interventions in the artistic work cannot be ruled out when preventive measures are implemented.

Differences between endogenous and exogenous emotion inhibition in the human brain.

PubMed

Kühn, Simone; Haggard, Patrick; Brass, Marcel

2014-05-01

The regulation of emotions is an integral part of our mental health. It has only recently been investigated using brain imaging techniques. In most studies, participants are instructed by a cue to inhibit a specific emotional reaction. The aim of the present study was to investigate the alternative situation where a person decides to inhibit an emotion as an act of endogenous self-control. Healthy participants viewed highly arousing pictures with negative valence. In the endogenous condition, participants could freely choose on each trial to inhibit or feel the emotions elicited by the picture. In an exogenous condition, a visual cue instructed them to either feel or inhibit the emotion elicited by the picture. Participants' subjective ratings of intensity of experienced emotion showed an interaction effect between source of control (endogenous/exogenous) and feel/inhibit based on a stronger modulation between feel and inhibition for the endogenous compared to the exogenous condition. Endogenous inhibition of emotions was associated with dorso-medial prefrontal cortex activation, whereas exogenous inhibition was found associated with lateral prefrontal cortex activation. Thus, the brain regions for both endogenous and exogenous inhibition of emotion are highly similar to those for inhibition of motor actions in Brass and Haggard (J Neurosci 27:9141-9145, 2007), Kühn et al. (Hum Brain Mapp 30:2834-2843, 2009). Functional connectivity analyses showed that dorsofrontomedial cortex exerts greater control onto pre-supplementary motor area during endogenous inhibition compared to endogenous feel. This functional dissociation between an endogenous, fronto-medial and an exogenous, fronto-lateral inhibition centre has important implications for our understanding of emotion regulation in health and psychopathology.

BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.

PubMed

Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

2015-06-02

Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell's response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells.

Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate

PubMed Central

Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

2016-01-01

Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers. PMID:27374086

VEGF-A is increased in exogenous endophthalmitis.

PubMed

Seamone, Mark E; Lewis, Darrell R; Haidl, Ian D; Gupta, R Rishi; O' Brien, Daniel M; Dickinson, John; Samad, Arif; Marshall, Jean S; Cruess, Alan F

2017-06-01

Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8). Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole (p < 0.001). VEGF-A was significantly upregulated in individuals with exogenous endophthalmitis after cataract surgery (p = 0.001), vitrectomy (p = 0.024), and intravitreal injection (p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations (p > 0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 (p = 0.028). We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Exogenous Application of GABA Improves PEG-Induced Drought Tolerance Positively Associated with GABA-Shunt, Polyamines, and Proline Metabolism in White Clover.

PubMed

Yong, Bin; Xie, Huan; Li, Zhou; Li, Ya-Ping; Zhang, Yan; Nie, Gang; Zhang, Xin-Quan; Ma, Xiao; Huang, Lin-Kai; Yan, Yan-Hong; Peng, Yan

2017-01-01

In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ 1 -pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism.

Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate.

PubMed

Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

2016-07-26

Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers.

Exogenous Application of GABA Improves PEG-Induced Drought Tolerance Positively Associated with GABA-Shunt, Polyamines, and Proline Metabolism in White Clover

PubMed Central

Yong, Bin; Xie, Huan; Li, Zhou; Li, Ya-Ping; Zhang, Yan; Nie, Gang; Zhang, Xin-Quan; Ma, Xiao; Huang, Lin-Kai; Yan, Yan-Hong; Peng, Yan

2017-01-01

In order to investigate the physiological effects of exogenous γ-aminobutyric acid (GABA) on drought tolerance in white clover (Trifolium repens), GABA shunt, polyamines (PAs), and proline (Pro) metabolism were examined after plants pretreated with or without GABA (8 mM) and then exposed to water or 15% PEG-induced drought stress in growth chamber. In this study, exogenous application of GABA effectively alleviated drought-induced damage in leaves, as reflected by significantly higher relative water content, lower electrolyte leakage, lipid peroxidation, and leaf wilt. Exogenous GABA further promoted drought-induced increases in GABA transaminase and alpha ketone glutarate dehydrogenase activities, but inhibited glutamate decarboxylase activity under both control and drought conditions, resulting in an increase in endogenous glutamate (Glu) and GABA content. Besides, exogenous GABA could well accelerated PAs synthesis and suppressed PAs catabolism, which lead to the extremely enhanced different types of PAs content (free Put and Spd, insoluble bound Spd and Spm, soluble conjugated Spd and Spm, and total Put, Spd and Spm) under drought stress. In addition, exogenous GABA application further activated drought-induced Δ1-pyrroline-5-carboxylate synthetase and proline dehydrogenase activities, but suppressed drought-facilitated ornithine -δ-amino transferase activities, leading to a higher Pro accumulation and metabolism in GABA-pretreated plants in the middle and last period of drought. The results suggested that increased endogenous GABA by exogenous GABA treatment could improve drought tolerance of white clover associated with a positive regulation in the GABA-shunt, PAs and Pro metabolism. PMID:29312009

Auxin synthesis gene tms1 driven by tuber-specific promoter alters hormonal status of transgenic potato plants and their responses to exogenous phytohormones.

PubMed

Kolachevskaya, Oksana O; Sergeeva, Lidiya I; Floková, Kristyna; Getman, Irina A; Lomin, Sergey N; Alekseeva, Valeriya V; Rukavtsova, Elena B; Buryanov, Yaroslav I; Romanov, Georgy A

2017-03-01

Ectopic auxin overproduction in transgenic potato leads to enhanced productivity accompanied with concerted and occasional changes in hormonal status, and causing altered response of transformants to exogenous auxin or cytokinin. Previously, we generated potato transformants expressing Agrobacterium-derived auxin synthesis gene tms1 driven by tuber-specific patatin gene promoter (B33-promoter). Here, we studied the endogenous hormonal status and the response to exogenous phytohormones in tms1 transformants cultured in vitro. Adding indole-3-acetic acid (IAA) or kinetin to culture medium affected differently tuberization of tms1-transformed and control plants, depending also on sucrose content in the medium. Exogenous phytohormones ceased to stimulate the tuber initiation in transformants at high (5-8%) sucrose concentration, while in control plants the stimulation was observed in all experimental settings. Furthermore, exogenous auxin partly inhibited the tuber initiation, and exogenous cytokinin reduced the average tuber weight in most transformants at high sucrose content. The elevated auxin level in tubers of the transformants was accompanied with a decrease in content of cytokinin bases and their ribosides in tubers and most shoots. No concerted changes in contents of abscisic, jasmonic, salicylic acids and gibberellins in tubers were detected. The data on hormonal status indicated that the enhanced productivity of tms1 transformants was due to auxin and not mediated by other phytohormones. In addition, exogenous cytokinin was shown to upregulate the expression of genes encoding orthologs of auxin receptors. Overall, the results showed that tms1 expression and local increase in IAA level in transformants affect both the balance of endogenous cytokinins and the dynamics of tuberization in response to exogenous hormones (auxin, cytokinin), the latter reaction depending also on the carbohydrate supply. We introduce a basic model for the hormonal network controlling tuberization.

Proteomic and physiological analyses reveal the role of exogenous spermidine on cucumber roots in response to Ca(NO3)2 stress.

PubMed

Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng

2018-05-01

The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation

PubMed Central

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details. PMID:26528912

Computational Characterization of Exogenous MicroRNAs that Can Be Transferred into Human Circulation.

PubMed

Shu, Jiang; Chiang, Kevin; Zempleni, Janos; Cui, Juan

2015-01-01

MicroRNAs have been long considered synthesized endogenously until very recent discoveries showing that human can absorb dietary microRNAs from animal and plant origins while the mechanism remains unknown. Compelling evidences of microRNAs from rice, milk, and honeysuckle transported to human blood and tissues have created a high volume of interests in the fundamental questions that which and how exogenous microRNAs can be transferred into human circulation and possibly exert functions in humans. Here we present an integrated genomics and computational analysis to study the potential deciding features of transportable microRNAs. Specifically, we analyzed all publicly available microRNAs, a total of 34,612 from 194 species, with 1,102 features derived from the microRNA sequence and structure. Through in-depth bioinformatics analysis, 8 groups of discriminative features have been used to characterize human circulating microRNAs and infer the likelihood that a microRNA will get transferred into human circulation. For example, 345 dietary microRNAs have been predicted as highly transportable candidates where 117 of them have identical sequences with their homologs in human and 73 are known to be associated with exosomes. Through a milk feeding experiment, we have validated 9 cow-milk microRNAs in human plasma using microRNA-sequencing analysis, including the top ranked microRNAs such as bta-miR-487b, miR-181b, and miR-421. The implications in health-related processes have been illustrated in the functional analysis. This work demonstrates the data-driven computational analysis is highly promising to study novel molecular characteristics of transportable microRNAs while bypassing the complex mechanistic details.

The Arabidopsis Phytocystatin AtCYS5 Enhances Seed Germination and Seedling Growth under Heat Stress Conditions.

PubMed

Song, Chieun; Kim, Taeyoon; Chung, Woo Sik; Lim, Chae Oh

2017-08-01

Phytocystatins (PhyCYSs) are plant-specific proteinaceous inhibitors that are implicated in protein turnover and stress responses. Here, we characterized a PhyCYS from Arabidopsis thaliana , which was designated AtCYS5. RT-qPCR analysis showed that the expression of AtCYS5 in germinating seeds was induced by heat stress (HS) and exogenous abscisic acid (ABA) treatment. Analysis of the expression of the β -glucuronidase reporter gene under the control of the AtCYS5 promoter showed that AtCYS5 expression during seed germination was induced by HS and ABA. Constitutive overexpression of AtCYS5 driven by the cauliflower mosaic virus 35S promoter led to enhanced HS tolerance in transgenic Arabidopsis , which was characterized by higher fresh weight and root length compared to wild-type (WT) and knockout ( cys5 ) plants grown under HS conditions. The HS tolerance of At-CYS5 -overexpressing transgenic plants was associated with increased insensitivity to exogenous ABA during both seed germination and post-germination compared to WT and cys5 . Although no HS elements were identified in the 5'-flanking region of AtCYS5 , canonical ABA-responsive elements (ABREs) were detected. AtCYS5 was upregulated in ABA-treated protoplasts transiently co-expressing this gene and genes encoding bZIP ABRE-binding factors (ABFs and AREB3). In the absence of ABA, ABF1 and ABF3 directly bound to the ABREs in the AtCYS5 promoter, which activated the transcription of this gene in the presence of ABA. These results suggest that an ABA-dependent pathway plays a positive role in the HS-responsive expression of AtCYS5 during seed germination and post-germination growth.

Lipoxin A4, a 5-lipoxygenase pathway metabolite, modulates immune response during acute respiratory tularemia.

PubMed

Singh, Anju; Rahman, Tabassum; Bartiss, Rose; Arabshahi, Alireza; Prasain, Jeevan; Barnes, Stephen; Musteata, Florin Marcel; Sellati, Timothy J

2017-02-01

Respiratory infection with Francisella tularensis (Ft) is characterized by a muted, acute host response, followed by sepsis-like syndrome that results in death. Infection with Ft establishes a principally anti-inflammatory environment that subverts host-cell death programs to facilitate pathogen replication. Although the role of cytokines has been explored extensively, the role of eicosanoids in tularemia pathogenesis is not fully understood. Given that lipoxin A 4 (LXA 4 ) has anti-inflammatory properties, we investigated whether this lipid mediator affects host responses manifested early during infection. The addition of exogenous LXA 4 inhibits PGE 2 release by Ft-infected murine monocytes in vitro and diminishes apoptotic cell death. Tularemia pathogenesis was characterized in 5‑lipoxygenase-deficient (Alox5 -/- ) mice that are incapable of generating LXA 4 Increased release of proinflammatory cytokines and chemokines, as well as increased apoptosis, was observed in Alox5 -/- mice as compared with their wild-type counterparts. Alox5 -/- mice also exhibited elevated recruitment of neutrophils during the early phase of infection and increased resistance to lethal challenge. Conversely, administration of exogenous LXA 4 to Alox5 -/- mice made them more susceptible to infection thus mimicking wild-type animals. Taken together, our results suggest that 5-LO activity is a critical regulator of immunopathology observed during the acute phase of respiratory tularemia, regulating bacterial burden and neutrophil recruitment and production of proinflammatory modulators and increasing morbidity and mortality. These studies identify a detrimental role for the 5-LO-derived lipid mediator LXA 4 in Ft-induced immunopathology. Targeting this pathway may have therapeutic benefit as an adjunct to treatment with antibiotics and conventional antimicrobial peptides, which often have limited efficacy against intracellular bacteria. © Society for Leukocyte Biology.

Fructose-maltodextrin ratio in a carbohydrate-electrolyte solution differentially affects exogenous carbohydrate oxidation rate, gut comfort, and performance.

PubMed

O'Brien, Wendy J; Rowlands, David S

2011-01-01

Solutions containing multiple carbohydrates utilizing different intestinal transporters (glucose and fructose) show enhanced absorption, oxidation, and performance compared with single-carbohydrate solutions, but the impact of the ratio of these carbohydrates on outcomes is unknown. In a randomized double-blind crossover, 10 cyclists rode 150 min at 50% peak power, then performed an incremental test to exhaustion, while ingesting artificially sweetened water or one of three carbohydrate-salt solutions comprising fructose and maltodextrin in the respective following concentrations: 4.5 and 9% (0.5-Ratio), 6 and 7.5% (0.8-Ratio), and 7.5 and 6% (1.25-Ratio). The carbohydrates were ingested at 1.8 g/min and naturally (13)C-enriched to permit evaluation of oxidation rate by mass spectrometry and indirect calorimetry. Mean exogenous carbohydrate oxidation rates were 1.04, 1.14, and 1.05 g/min (coefficient of variation 20%) in 0.5-, 0.8-, and 1.25-Ratios, respectively, representing likely small increases in 0.8-Ratio of 11% (90% confidence limits; ± 4%) and 10% (± 4%) relative to 0.5- and 1.25-Ratios, respectively. Comparisons of fat and total and endogenous carbohydrate oxidation rates between solutions were unclear. Relative to 0.5-Ratio, there were moderate improvements to peak power with 0.8- (3.6%; 99% confidence limits ± 3.5%) and 1.25-Ratio (3.0%; ± 3.7%) but unclear with water (0.4%; ± 4.4%). Increases in stomach fullness, abdominal cramping, and nausea were lowest with the 0.8- followed by the 1.25-Ratio solution. At high carbohydrate-ingestion rate, greater benefits to endurance performance may result from ingestion of 0.8- to 1.25-Ratio fructose-maltodextrin solutions. Small perceptible improvements in gut comfort favor the 0.8-Ratio and provide a clearer suggestion of mechanism than the relationship with exogenous carbohydrate oxidation.

Cigarette smoke inhibits efferocytosis via deregulation of sphingosine kinase signaling: reversal with exogenous S1P and the S1P analogue FTY720.

PubMed

Tran, Hai B; Barnawi, Jameel; Ween, Miranda; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Reynolds, Paul N; Pitson, Stuart M; Davies, Lorena T; Haberberger, Rainer; Hodge, Sandra

2016-07-01

Alveolar macrophages from chronic obstructive pulmonary disease patients and cigarette smokers are deficient in their ability to phagocytose apoptotic bronchial epithelial cells (efferocytosis). We hypothesized that the defect is mediated via inhibition of sphingosine kinases and/or their subcellular mislocalization in response to cigarette smoke and can be normalized with exogenous sphingosine-1-phosphate or FTY720 (fingolimod), a modulator of sphingosine-1-phosphate signaling, which has been shown to be clinically useful in multiple sclerosis. Measurement of sphingosine kinase 1/2 activities by [(32)P]-labeled sphingosine-1-phosphate revealed a 30% reduction of sphingosine kinase 1 (P < 0.05) and a nonsignificant decrease of sphingosine kinase 2 in THP-1 macrophages after 1 h cigarette smoke extract exposure. By confocal analysis macrophage sphingosine kinase 1 protein was normally localized to the plasma membrane and cytoplasm and sphingosine kinase 2 to the nucleus and cytoplasm but absent at the cell surface. Cigarette smoke extract exposure (24 h) led to a retraction of sphingosine kinase 1 from the plasma membrane and sphingosine kinase 1/2 clumping in the Golgi domain. Selective inhibition of sphingosine kinase 2 with 25 µM ABC294640 led to 36% inhibition of efferocytosis (P < 0.05); 10 µM sphingosine kinase inhibitor/5C (sphingosine kinase 1-selective inhibitor) induced a nonsignificant inhibition of efferocytosis, but its combination with ABC294640 led to 56% inhibition (P < 0.01 vs. control and < 0.05 vs. single inhibitors). Cigarette smoke-inhibited efferocytosis was significantly (P < 0.05) reversed to near-control levels in the presence of 10-100 nM exogenous sphingosine-1-phosphate or FTY720, and FTY720 reduced cigarette smoke-induced clumping of sphingosine kinase 1/2 in the Golgi domain. These data strongly support a role of sphingosine kinase 1/2 in efferocytosis and as novel therapeutic targets in chronic obstructive pulmonary disease. © Society for Leukocyte Biology.

Modeling an exogenic origin for the equatorial ridge on Iapetus

NASA Astrophysics Data System (ADS)

Stickle, Angela M.; Roberts, James H.

2018-06-01

Iapetus has a ridge along the equator that extends continuously for more than 110° in longitude. Parts of the ridge rise as much as 20 km above the surrounding terrains. Most models for the formation of this enigmatic ridge are endogenic, generally requiring the formation of a fast-spinning Iapetus with an oblate shape due to the rotation speed. Many of these require specific scenarios and have constraining parameters in order to generate a ridge comparable to what is seen today. An exogenic formation mechanism has also been proposed, that the ridge represents the remains of an early ring system around Iapetus that collapsed onto the surface. Thus far, none of the models have conclusively identified the origin of the ridge. In this study, an exogenic origin for the ridge is assumed, which is derived from a collapsing disk of debris around Iapetus, without invoking any specific model for the generation of the debris disk. Here, we evaluate whether it is possible to generate a ridge of the size and shape as observed by simulating the impact of the collapsing debris using the CTH hydrocode. Pi-scaling calculations suggest that extremely oblique impact angles (1°-10°) are needed to add to ridge topography. These extreme impact angles severely reduce the cratering efficiency compared to a vertical impact, adding material rather than eroding it during crater formation. Furthermore, material is likely to be excavated at low angles, enhancing downrange accumulation. Multiple impacts from debris pieces will heighten this effect. Because infalling debris is predicted to impact at extremely low angles, both of these effects might have contributed to ridge formation on Iapetus. The extreme grazing angles of the impacts modeled here decouple much of the projectile energy from the target, and impact heating of the surface is not significant. These models suggest that a collapsing disk of debris should have been able to build topography to create a ridge around Iapetus.

Eutrophication triggers contrasting multilevel feedbacks on litter accumulation and decomposition in fens.

PubMed

Emsens, W-J; Aggenbach, C J S; Grootjans, A P; Nfor, E E; Schoelynck, J; Struyf, E; van Diggelen, R

2016-10-01

Eutrophication is a major threat for the persistence of nutrient-poor fens, as multilevel feedbacks on decomposition rates could trigger carbon loss and increase nutrient cycling. Here, we experimentally investigate the effects of macronutrient (NPK) enrichment on litter quality of six species of sedge (Carex sp.), which we relate to litter decomposition rates in a nutrient-poor and nutrient-rich environment. Our research focused on four levels: we examined how eutrophication alters (1) fresh litter production ("productivity shift"), (2) litter stoichiometry within the same species ("intraspecific shift"), (3) overall litter stoichiometry of the vegetation under the prediction that low-competitive species are outcompeted by fast-growing competitors ("interspecific shift"), and (4) litter decomposition rates due to an altered external environment (e.g., shifts in microbial activity; "exogenous shift"). Eutrophication triggered a strong increase in fresh litter production. Moreover, individuals of the same species produced litter with lower C:N and C:P ratios, higher K contents, and lower lignin, Ca and Mg contents (intraspecific shift), which increased litter decomposability. In addition, species typical for eutrophic conditions produced more easily degradable litter than did species typical for nutrient-poor conditions (interspecific shift). However, the effects of nutrient loading of the external environment (exogenous shift) were contradictory. Here, interactions between litter type and ambient nutrient level indicate that the (exogenous) effects of eutrophication on litter decomposition rates are strongly dependent of litter quality. Moreover, parameters of litter quality only correlated with decomposition rates for litter incubated in nutrient-poor environments, but not in eutrophic environments. This suggests that rates of litter decomposition can be uncoupled from litter stoichiometry under eutrophic conditions. In conclusion, our results show that eutrophication affects litter accumulation and -decomposition at multiple levels, in which stimulatory and inhibitory effects interact. The cumulative effect of these interactions ultimately determine whether peatlands remain sinks or become sources of carbon under eutrophic conditions. © 2016 by the Ecological Society of America.

Soldier-Robot Team Communication: An Investigation of Exogenous Orienting Visual Display Cues and Robot Reporting Preferences

DTIC Science & Technology

2018-02-12

usability preference. Results under the second focus showed that the frequency with which participants expected status updates differed depending upon the...assistance requests for both navigational route and building selection depending on the type of exogenous visual cues displayed? 3) Is there a difference...in response time to visual reports for both navigational route and building selection depending on the type of exogenous visual cues displayed? 4

Measuring Exposure Opportunities: Using Exogenous Measures in Assessing Effects of Media Exposure on Smoking Outcomes

PubMed Central

Liu, Jiaying; Hornik, Robert

2016-01-01

Measurement of exposure has long been one of the most central and fundamental issues in communication research. While self-reported measures remain dominant in the field, alternative approaches such as exogenous or hybrid measures have received increasing scholarly attention and been employed in various contexts for the estimation of media exposure; however, systematic scrutiny of such measures is thin. This study aims to address the gap by systematically reviewing the studies which utilized exogenous or hybrid exposure measures for examining the effects of media exposure on tobacco-related outcomes. We then proceed to discuss the strengths and weaknesses, current developments in this class of measurement, drawing some implications for the appropriate utilization of exogenous and hybrid measures. PMID:27746848

Surfactant for Pediatric Acute Lung Injury

PubMed Central

Willson, Douglas F.; Chess, Patricia R.; Notter, Robert H.

2008-01-01

Synopsis This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations. PMID:18501754

Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

NASA Astrophysics Data System (ADS)

Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin

2011-10-01

We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

Visualization of metallodrugs in single cells by secondary ion mass spectrometry imaging.

PubMed

Wu, Kui; Jia, Feifei; Zheng, Wei; Luo, Qun; Zhao, Yao; Wang, Fuyi

2017-07-01

Secondary ion mass spectrometry, including nanoscale secondary ion mass spectrometry (NanoSIMS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), has emerged as a powerful tool for biological imaging, especially for single cell imaging. SIMS imaging can provide information on subcellular distribution of endogenous and exogenous chemicals, including metallodrugs, from membrane through to cytoplasm and nucleus without labeling, and with high spatial resolution and chemical specificity. In this mini-review, we summarize recent progress in the field of SIMS imaging, particularly in the characterization of the subcellular distribution of metallodrugs. We anticipate that the SIMS imaging method will be widely applied to visualize subcellular distributions of drugs and drug candidates in single cells, exerting significant influence on early drug evaluation and metabolism in medicinal and pharmaceutical chemistry. Recent progress of SIMS applications in characterizing the subcellular distributions of metallodrugs was summarized.

Lipopolysaccharide and Aldoheptose Biosynthesis in Transketolase Mutants of Salmonella typhimurium

PubMed Central

Eidels, L.; Osborn, M. J.

1971-01-01

Genetic and biochemical evidence that sedoheptulose-7-phosphate is an obligatory precursor of the L-glycero-D-mannoheptose residues of the lipopolysaccharide of Salmonella was obtained by isolation and characterization of transketolase-negative mutants of Salmonella typhimurium. These mutants, which are defective in synthesis of sedoheptulose-7-phosphate, were found to produce an incomplete heptose-deficient lipopolysaccharide, and were also sensitive to bile salts, a characteristic property of heptose-deficient mutants. Phenotypic repair of the defect in lipopolysaccharide synthesis was obtained by addition of exogenous sedoheptulose-7-phosphate to growing cultures of the mutant strains. Characterization of revertants isolated either as transketolase-positive or heptose-positive provided further evidence that the heptose deficiency resulted from mutation at the transketolase locus. On the basis of these findings a possible pathway for conversion of sedoheptulose-7-phosphate to L-glycero-D-mannoheptose is proposed. PMID:4942911

Transcutaneous measurement of glomerular filtration rate in conscious laboratory animals: state of the art and future perspectives

NASA Astrophysics Data System (ADS)

Friedemann, Jochen; Schock-Kusch, Daniel; Shulhevich, Yury

2017-02-01

Transcutaneous measurement of Glomerular Filtration Rate (tGFR) is now frequently used in preclinical in vivo animal studies. tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis. A description of the measurement device and its many applications, along with examples from the recent literature will be given. We will highlight the fields of interest in which the system is used and give an overview about its performance versus endogenous and other exogenous methods of GFR measurement. A special focus will be put on the precision of tGFR compared to standard measurements employed in the research setting.

Exogenous attention influences visual short-term memory in infants.

PubMed

Ross-Sheehy, Shannon; Oakes, Lisa M; Luck, Steven J

2011-05-01

Two experiments examined the hypothesis that developing visual attentional mechanisms influence infants' Visual Short-Term Memory (VSTM) in the context of multiple items. Five- and 10-month-old infants (N = 76) received a change detection task in which arrays of three differently colored squares appeared and disappeared. On each trial one square changed color and one square was cued; sometimes the cued item was the changing item, and sometimes the changing item was not the cued item. Ten-month-old infants exhibited enhanced memory for the cued item when the cue was a spatial pre-cue (Experiment 1) and 5-month-old infants exhibited enhanced memory for the cued item when the cue was relative motion (Experiment 2). These results demonstrate for the first time that infants younger than 6 months can encode information in VSTM about individual items in multiple-object arrays, and that attention-directing cues influence both perceptual and VSTM encoding of stimuli in infants as in adults.

Fluorescent probes for the simultaneous detection of multiple analytes in biology.

PubMed

Kolanowski, Jacek L; Liu, Fei; New, Elizabeth J

2018-01-02

Many of the key questions facing cellular biology concern the location and concentration of chemical species, from signalling molecules to metabolites to exogenous toxins. Fluorescent sensors (probes) have revolutionised the understanding of biological systems through their exquisite sensitivity to specific analytes. Probe design has focussed on selective sensors for individual analytes, but many of the most pertinent biological questions are related to the interaction of more than one chemical species. While it is possible to simultaneously use multiple sensors for such applications, data interpretation will be confounded by the fact that sensors will have different uptake, localisation and metabolism profiles. An alternative solution is to instead use a single probe that responds to two analytes, termed a dual-responsive probe. Recent progress in this field has yielded exciting probes, some of which have demonstrated biological application. Here we review work that has been carried out to date, and suggest future research directions that will harness the considerable potential of dual-responsive fluorescent probes.

PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

PubMed Central

Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

2007-01-01

We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

Nuclear magnetic resonance spectroscopy in the structure elucidation and biosynthesis of natural products

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

Meksuriyen, D.

1988-01-01

Examination of a chloroform extract of Dracaena loureiri Gagnep (Agavaceae), a Thia medicinal plant possessing antibacterial activity, has led to the isolation of fifteen flavenoids. The biogenic relationships among these flavenoids isolated were briefly discussed. Definition of the skeleton and the unambiguous assignment of all of the protons of the isolates was achieved through extensive 2D-homonuclear chemical shift correlation, nuclear Overhauser effect (NOE) difference spectroscopy and 2D-NOE experiments. The {sup 1}H and {sup 13}C NMR spectra of staurosporine, a potent biologically active agent from Streptomyces staurosporeus, were unambiguously assigned by using 2D homonuclear chemical shift correlation, NOE, {sup 1}H-detected heteronuclearmore » multiple-quantum coherence via direct coupling and via multiple-bond coupling for resonance assignments of protonated and nonprotonated carbons, respectively. S. Staurosporeus was found to utilize endogenous and exogenous D- and L-isomers of trytophan in the production of staurosporine. The biosynthesis of staurosporine was examined by employing carbon-14, tritium, and carbon-13 labeled precursors.« less

Effect of exogenous inoculants on enhancing oil recovery and indigenous bacterial community dynamics in long-term field pilot of low permeability reservoir.

PubMed

Li, Jing; Xue, Shuwen; He, Chunqiu; Qi, Huixia; Chen, Fulin; Ma, Yanling

2018-03-20

Pseudomonas aeruginosa DN1 strain and Bacillus subtilis QHQ110 strain were chosen as rhamnolipid and lipopeptide producer respectively, to evaluate the efficiency of exogenous inoculants on enhancing oil recovery (EOR) and to explore the relationship between injected bacteria and indigenous bacterial community dynamics in long-term filed pilot of Hujianshan low permeability water-flooded reservoir for 26 months. Core-flooding tests showed that the oil displacement efficiency increased by 18.46% with addition of exogenous consortia. Bacterial community dynamics using quantitative PCR and high-throughput sequencing revealed that the exogenous inoculants survived and could live together with indigenous bacterial populations. They gradually became the dominant community after the initial activation, while their comparative advantage weakened continually after 3 months of the first injection. The bacterial populations did not exert an observable change in the process of the second injection of exogenous inoculants. On account of facilitating oil emulsification and accelerating bacterial growth with oil as the carbon source by the injection of exogenous consortia, γ-proteobacteria was finally the prominent bacterial community at class level varying from 25.55 to 32.67%, and the dominant bacterial populations were increased by 2-3 orders of magnitude during the whole processes. The content of organic acids and rhamnolipids in reservoir were promoted with the change of bacterial community diversity, respectively. Cumulative oil increments reached 26,190 barrels for 13 months after the first injection, and 55,947 barrels of oil had been accumulated in all of A20 wells block through two rounds of bacterial consortia injection. The performance of EOR has a cumulative improvement by the injection of exogenous inoculants without observable inhibitory effect on the indigenous bacterial populations, demonstrating the application potential in low permeability water-flooded reservoirs.

Analysis of exogenous components of mortality risks.

PubMed

Blinkin, V L

1998-04-01

A new technique for deriving exogenous components of mortality risks from national vital statistics has been developed. Each observed death rate Dij (where i corresponds to calendar time (year or interval of years) and j denotes the number of corresponding age group) was represented as Dij = Aj + BiCj, and unknown quantities Aj, Bi, and Cj were estimated by a special procedure using the least-squares principle. The coefficients of variation do not exceed 10%. It is shown that the term Aj can be interpreted as the endogenous and the second term BiCj as the exogenous components of the death rate. The aggregate of endogenous components Aj can be described by a regression function, corresponding to the Gompertz-Makeham law, A(tau) = gamma + beta x e alpha tau, where gamma, beta, and alpha are constants, tau is age, A(tau) [symbol: see text] tau = tau j identical to A(tau j) identical to Aj and tau j is the value of age tau in jth age group. The coefficients of variation for such a representation does not exceed 4%. An analysis of exogenous risk levels in the Moscow and Russian populations during 1980-1995 shows that since 1992 all components of exogenous risk in the Moscow population had been increasing up to 1994. The greatest contribution to the total level of exogenous risk was lethal diseases, and their death rate was 387 deaths per 100,000 persons in 1994, i.e., 61.9% of all deaths. The dynamics of exogenous mortality risk change during 1990-1994 in the Moscow population and in the Russian population without Moscow had been identical: the risk had been increasing and its value in the Russian population had been higher than that in the Moscow population.

Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming.

PubMed

Choi, Kevin; Weber, Jean-Michel

2016-03-15

This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed (Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production (Ra glucose) and disposal (Rd glucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucrit or the cost of transport. Results show that graded swimming causes no change in Ra and Rd glucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg(-1)·min(-1) and boost glucose disposal to 40.1 ± 13 μmol·kg(-1)·min(-1). These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucrit because the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise. Copyright © 2016 the American Physiological Society.

Fructose and Sucrose Intake Increase Exogenous Carbohydrate Oxidation during Exercise

PubMed Central

Trommelen, Jorn; Fuchs, Cas J.; Beelen, Milou; Lenaerts, Kaatje; Jeukendrup, Asker E.; Cermak, Naomi M.; van Loon, Luc J. C.

2017-01-01

Peak exogenous carbohydrate oxidation rates typically reach ~1 g·min−1 during exercise when ample glucose or glucose polymers are ingested. Fructose co-ingestion has been shown to further increase exogenous carbohydrate oxidation rates. The purpose of this study was to assess the impact of fructose co-ingestion provided either as a monosaccharide or as part of the disaccharide sucrose on exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists. Ten trained male cyclists (VO2peak: 65 ± 2 mL·kg−1·min−1) cycled on four different occasions for 180 min at 50% Wmax during which they consumed a carbohydrate solution providing 1.8 g·min−1 of glucose (GLU), 1.2 g·min−1 glucose + 0.6 g·min−1 fructose (GLU + FRU), 0.6 g·min−1 glucose + 1.2 g·min−1 sucrose (GLU + SUC), or water (WAT). Peak exogenous carbohydrate oxidation rates did not differ between GLU + FRU and GLU + SUC (1.40 ± 0.06 vs. 1.29 ± 0.07 g·min−1, respectively, p = 0.999), but were 46% ± 8% higher when compared to GLU (0.96 ± 0.06 g·min−1: p < 0.05). In line, exogenous carbohydrate oxidation rates during the latter 120 min of exercise were 46% ± 8% higher in GLU + FRU or GLU + SUC compared with GLU (1.19 ± 0.12, 1.13 ± 0.21, and 0.82 ± 0.16 g·min−1, respectively, p < 0.05). We conclude that fructose co-ingestion (0.6 g·min−1) with glucose (1.2 g·min−1) provided either as a monosaccharide or as sucrose strongly increases exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists. PMID:28230742

Fructose and Sucrose Intake Increase Exogenous  Carbohydrate Oxidation during Exercise.

PubMed

Trommelen, Jorn; Fuchs, Cas J; Beelen, Milou; Lenaerts, Kaatje; Jeukendrup, Asker E; Cermak, Naomi M; van Loon, Luc J C

2017-02-20

Peak exogenous carbohydrate oxidation rates typically reach ~1 g∙min-1 during exercise when ample glucose or glucose polymers are ingested. Fructose co-ingestion has been shown to further increase exogenous carbohydrate oxidation rates. The purpose of this study was to assess the impact of fructose co-ingestion provided either as a monosaccharide or as part of the disaccharide sucrose on exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists. Ten trained male cyclists (VO2peak: 65 ± 2 mL∙kg-1∙min-1) cycled on four different occasions for 180 min at 50% Wmax during which they consumed a carbohydrate solution providing 1.8 g∙min-1 of glucose (GLU), 1.2 g∙min-1 glucose + 0.6 g∙min-1 fructose (GLU + FRU), 0.6 g∙min-1 glucose + 1.2 g∙min-1 sucrose (GLU + SUC), or water (WAT). Peak exogenous carbohydrate oxidation rates did not differ between GLU + FRU and GLU + SUC (1.40 ± 0.06 vs. 1.29 ± 0.07 g∙min-1, respectively, p = 0.999), but were 46% ± 8% higher when compared to GLU (0.96 ± 0.06 g∙min-1: p < 0.05). In line, exogenous carbohydrate oxidation rates during the latter 120 min of exercise were 46% ± 8% higher in GLU + FRU or GLU + SUC compared with GLU (1.19 ± 0.12, 1.13 ± 0.21, and 0.82 ± 0.16 g∙min-1, respectively, p < 0.05). We conclude that fructose co-ingestion (0.6 g∙min-1) with glucose (1.2 g∙min-1) provided either as a monosaccharide or as sucrose strongly increases exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists.

Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming

PubMed Central

Choi, Kevin

2015-01-01

This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed (Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production (Ra glucose) and disposal (Rd glucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucrit or the cost of transport. Results show that graded swimming causes no change in Ra and Rd glucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg−1·min−1 and boost glucose disposal to 40.1 ± 13 μmol·kg−1·min−1. These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucrit because the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise. PMID:26719305

Effect of Exogenous Phytase Addition on Soil Phosphatase Activities: a Fluorescence Spectroscopy Study.

PubMed

Yang, Xiao-zhu; Chen, Zhen-hua; Zhang, Yu-lan; Chen, Li-jun

2015-05-01

The utilization of organic phosphorus (P) has directly or indirectly improved after exogenous phytase was added to soil. However, the mechanism by which exogenous phytase affected the soil phosphatases (phosphomonoesterase and phosphodiesterase) activities was not clear. The present work was aimed to study red soil, brown soil and cinnamon soil phosphomonoesterase (acid and alkaline) (AcP and AlP) and phosphodiesterase (PD) activities responding to the addition of exogenous phytase (1 g phytase/50 g air dry soil sample) based on the measurements performed via a fluorescence detection method combined with 96 microplates using a TECAN Infinite 200 Multi-Mode Microplate Reader. The results indicated that the acid phosphomonoesterase activity was significantly enhanced in red soil (p≤0. 01), while it was significantly reduced in cinnamon soil; alkaline phosphomonoesterase activity was significantly enhanced in cinnamon soil (p≤ 0. 01), while it was significantly reduced in red soil; phosphodiesterase activity was increased in three soils but it was significantly increased in brown soil (p≤0. 01) after the addition of exogenous phytase. The activities still remained strong after eight days in different soils, which indicated that exogenous phytase addition could be enhance soil phosphatases activities effectively. This effect was not only related to soil properties, such as pH and phosphorus forms, but might also be related to the excreted enzyme amount of the stimulating microorganism. Using fluorescence spectroscopy to study exogenous phytase addition influence on soil phosphatase activities was the first time at home and abroad. Compared with the conventional spectrophotometric method, the fluorescence microplate method is an accurate, fast and simple to use method to determine the relationships among the soil phosphatases activities.

Transcription factor FOXO1 promotes cell migration toward exogenous ATP via controlling P2Y1 receptor expression in lymphatic endothelial cells.

PubMed

Niimi, Kenta; Ueda, Mizuha; Fukumoto, Moe; Kohara, Misaki; Sawano, Toshinori; Tsuchihashi, Ryo; Shibata, Satoshi; Inagaki, Shinobu; Furuyama, Tatsuo

2017-08-05

Sprouting migration of lymphatic endothelial cell (LEC) is a pivotal step in lymphangiogenic process. However, its molecular mechanism remains unclear including effective migratory attractants. Meanwhile, forkhead transcription factor FOXO1 highly expresses in LEC nuclei, but its significance in LEC migratory activity has not been researched. In this study, we investigated function of FOXO1 transcription factor associated with LEC migration toward exogenous ATP which has recently gathered attentions as a cell migratory attractant. The transwell membrane assay indicated that LECs migrated toward exogenous ATP, which was impaired by FOXO1 knockdown. RT-PCR analysis showed that P2Y1, a purinergic receptor, expression was markedly reduced by FOXO1 knockdown in LECs. Moreover, P2Y1 blockage impaired LEC migration toward exogenous ATP. Western blot analysis revealed that Akt phosphorylation contributed to FOXO1-dependent LEC migration toward exogenous ATP and its blockage affected LEC migratory activity. Furthermore, luciferase reporter assay and ChIP assay suggested that FOXO1 directly bound to a conserved binding site in P2RY1 promoter and regulated its activity. These results indicated that FOXO1 serves a pivotal role in LEC migration toward exogenous ATP via direct transcriptional regulation of P2Y1 receptor. Copyright © 2017 Elsevier Inc. All rights reserved.

Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy.

PubMed

Huang, Kun; Gao, Lu; Yang, Ming; Wang, Jiliang; Wang, Zheng; Wang, Lin; Wang, Guobin; Li, Huili

2017-08-01

Angiotensin (Ang) Ⅱ-induced cardiac hypertrophy can deteriorate to heart failure, a leading cause of mortality. Endogenous Cathepsin V (CTSV) has been reported to be cardioprotective against hypertrophy. However, little is known about the effect of exogenous CTSV on cardiac hypertrophy. We used the human cardiomyocytes HCM as a cell model to investigate the effects of exogenous CTSV on Ang Ⅱ-induced cardiac cell hypertrophy. Cell surface area and expression of classical markers of hypertrophy were analyzed. We further explored the mechanism of CTSV cardioprotective by assessing the levels and activities of PI3K/Akt/mTOR and MAPK signaling pathway proteins. We found that pre-treating cardiomyocytes with CTSV could significantly inhibit Ang Ⅱ-induced hypertrophy. The mRNA expression of hypertrophy markers ANP, BNP and β-MHC was obviously elevated in Ang Ⅱ-treated cardiac cells. Whereas, exogenous CTSV effectively halted this elevation. Further study revealed that the protective effects of exogenous CTSV might be mediated by repressing the phosphorylation of proteins in the PI3K/Akt/mTOR and MAPK pathways. Based on our results, we concluded that exogenous CTSV inhibited Ang Ⅱ-induced hypertrophy in HCM cells by inhibiting PI3K/Akt/mTOR. This study provides experimental evidence for the application of CTSV protein for the treatment of cardiac hypertrophy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Verification of Bioanalytical Method for Quantification of Exogenous Insulin (Insulin Aspart) by the Analyser Advia Centaur® XP.

PubMed

Mihailov, Rossen; Stoeva, Dilyana; Pencheva, Blagovesta; Pentchev, Eugeni

2018-03-01

In a number of cases the monitoring of patients with type I diabetes mellitus requires measurement of the exogenous insulin levels. For the purpose of a clinical investigation of the efficacy of a medical device for application of exogenous insulin aspart, a verification of the method for measurement of this synthetic analogue of the hormone was needed. The information in the available medical literature for the measurement of the different exogenous insulin analogs is insufficient. Thus, verification was required to be in compliance with the active standards in Republic of Bulgaria. A manufactured method developed for ADVIA Centaur XP Immunoassay, Siemens Healthcare, was used which we verified using standard solutions and a patient serum pool by adding the appropriate quantity exogenous insulin aspart. The method was verified in accordance with the bioanalytical method verification criteria and regulatory requirements for using a standard method: CLIA chemiluminescence immunoassay ADVIA Centaur® XP. The following parameters are determined and monitored: intra-day precision and accuracy, inter-day precision and accuracy, limit of detection and lower limit of quantification, linearity, analytical recovery. The routine application of the method for measurement of immunoreactive insulin using the analyzer ADVIA Centaur® XP is directed to the measurement of endogenous insulin. The method is applicable for measuring different types of exogenous insulin, including insulin aspart.

Endogenously and exogenously driven selective sustained attention: Contributions to learning in kindergarten children.

PubMed

Erickson, Lucy C; Thiessen, Erik D; Godwin, Karrie E; Dickerson, John P; Fisher, Anna V

2015-10-01

Selective sustained attention is vital for higher order cognition. Although endogenous and exogenous factors influence selective sustained attention, assessment of the degree to which these factors influence performance and learning is often challenging. We report findings from the Track-It task, a paradigm that aims to assess the contribution of endogenous and exogenous factors to selective sustained attention within the same task. Behavioral accuracy and eye-tracking data on the Track-It task were correlated with performance on an explicit learning task. Behavioral accuracy and fixations to distractors during the Track-It task did not predict learning when exogenous factors supported selective sustained attention. In contrast, when endogenous factors supported selective sustained attention, fixations to distractors were negatively correlated with learning. Similarly, when endogenous factors supported selective sustained attention, higher behavioral accuracy was correlated with greater learning. These findings suggest that endogenously and exogenously driven selective sustained attention, as measured through different conditions of the Track-It task, may support different kinds of learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Exogenous lipoid pneumonia – a case report of a fire-eater

PubMed Central

Pielaszkiewicz-Wydra, Magdalena; Homola-Piekarska, Bożena; Szcześniak, Ewa; Ciołek-Zdun, Monika; Fall, Andrzej

2012-01-01

Summary Background: Exogenous lipoid pneumonia is an uncommon condition caused by inhalation or aspiration of a fatty substance. It usually presents as chronic respiratory illness mimicking interstitial lung diseases. Acute exogenous lipoid pneumonia is uncommon and typically is caused by an episode of aspiration of a large quantity of a petroleum-based product. Radiological findings vary and may imitate many other diseases. Case Report: We present a rare case of acute exogenous lipoid pneumonia in a fire-eater who aspirated liquid paraffin during his flame-blowing show (fire-eater’s lung). He was admitted to the hospital with productive cough, fever, hemoptysis, chest pain and dyspnea. Diagnosis was made on the basis of history of exposure to fatty substance, characteristic findings in CT examination and presence of lipid-laden macrophages in bronchoalveolar lavage fluid. Conclusions: Acute exogenous lipoid pneumonia is a very rare disease that typically occurs in fire-eaters and is called a fire-eater’s lung. The diagnosis is made on the basis of typical history and radiological, as well as histopathological findings. PMID:23269939

Feature integration and spatial attention: common processes for endogenous and exogenous orienting.

PubMed

Henderickx, David; Maetens, Kathleen; Soetens, Eric

2010-05-01

Briand (J Exp Psychol Hum Percept Perform 24:1243-1256, 1998) and Briand and Klein (J Exp Psychol Hum Percept Perform 13:228-241, 1987) demonstrated that spatial cueing effects are larger for detecting conjunction of features than for detecting simple features when spatial attention is oriented exogenously, and not when attention is oriented endogenously. Their results were interpreted as if only exogenous attention affects the posterior spatial attention system that performs the feature binding function attributed to spatial attention by Treisman's feature integration theory (FIT; 1980). In a series of 6 experiments, we attempted to replicate Briand's findings. Manipulations of distractor string size and symmetry of stimulus presentation left and right from fixation were implemented in Posner's cueing paradigm. The data indicate that both exogenous and endogenous cueing address the same attentional mechanism needed for feature binding. The results also limit the generalisability of Briand's proposal concerning the role of exogenous attention in feature integration. Furthermore, the importance to control the effect of unintended attentional capture in a cueing task is demonstrated.

[Advances in molecular mechanisms of adaptive immunity mediated by type I-E CRISPR/Cas system--A review].

PubMed

Sun, Dongchang; Qiu, Juanping

2016-01-04

To better adapt to the environment, prokaryocyte can take up exogenous genes (from bacteriophages, plasmids or genomes of other species) through horizontal gene transfer. Accompanied by the acquisition of exogenous genes, prokaryocyte is challenged by the invasion of 'selfish genes'. Therefore, to protect against the risk of gene transfer, prokaryocyte needs to establish mechanisms for selectively taking up or degrading exogenous DNA. In recent years, researchers discovered an adaptive immunity, which is mediated by the small RNA guided DNA degradation, prevents the invasion of exogenous genes in prokaryocyte. During the immune process, partial DNA fragments are firstly integrated.to the clustered regularly interspaced short palindromic repeats (CRISPR) located within the genome DNA, and then the mature CRISPR RNA transcript and the CRISPR associated proteins (Cas) form a complex CRISPR/Cas for degrading exogenous DNA. In this review, we will first briefly describe the CRISPR/Cas systems and then mainly focus on the recent advances of the function mechanism and the regulation mechanism of the type I-E CRISPR/Cas system in Escherichia coli.

Influence of exogenous lead pollution on enzyme activities and organic matter degradation in the surface of river sediment.

PubMed

Huang, Danlian; Xu, Juanjuan; Zeng, Guangming; Lai, Cui; Yuan, Xingzhong; Luo, Xiangying; Wang, Cong; Xu, Piao; Huang, Chao

2015-08-01

As lead is one of the most hazardous heavy metals in river ecosystem, the influence of exogenous lead pollution on enzyme activities and organic matter degradation in the surface of river sediment with high moisture content were studied at laboratory scale. The dynamic changes of urease, catalase, protease activities, organic matter content, and exchangeable or ethylenediaminetetraacetic acid (EDTA)-extractable Pb concentration in sediment were monitored during different levels of exogenous lead infiltrating into sediment. At the early stage of incubation, the activities of catalase and protease were inhibited, whereas the urease activities were enhanced with different levels of exogenous lead. Organic matter content in polluted sediment with exogenous lead was lower than control and correlated with enzyme activities. In addition, the effects of lead on the three enzyme activities were strongly time-dependent and catalase activities showed lower significant difference (P < 0.05) than urease and protease. Correlations between catalase activities and EDTA-extractable Pb in the experiment were significantly negative. The present findings will improve the understandings about the ecotoxicological mechanisms in sediment.

A proof for substitution of endogenous iron (II) in lipoxygenase by exogenous Cu2+.

PubMed

Cai, Yan; Xu, Hong; Xia, Yongmei; Su, Yafen; Fang, Yun

2010-10-01

Soybean lipoxygenase (LOX) contains endogenous iron (II) at the active site, which is important for the enzyme activity. The activity of LOX can be accelerated by some exogenous metal ions including Cu2+. However, the mechanism of the activity improvement caused by exogenous metal ions remains unclear, not only for LOX but for most other metalloenzymes. Meanwhile, the possibility that exogenous metal ions can displace endogenous iron (II) is still in discussion for a lack of a direct and quantitative proof. In this paper, a quantitative proof of replacing iron (II) inside LOX by exogenous Cu2+ was provided, simply using UV-Vis spectrometry with two indicators p-carboxylantipyrylazo and 9-(4-carboxyphenyl)-2,3,7-trihydroxyl-6-fluorine. A 0.56 microM free iron (II) was observed in the bulk solution after incubating 9.45 microM Cu2+ with 16.10 microM LOX at 20 degrees C for 5 min, which is in coincidence with the decrement of Cu2+ in the bulk solution (0.53 microM), implying that iron (II) was replaced by Cu2+.

Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

PubMed Central

Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

2016-01-01

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

Enhanced attention-dependent activity in the auditory cortex of older musicians.

PubMed

Zendel, Benjamin Rich; Alain, Claude

2014-01-01

Musical training improves auditory processing abilities, which correlates with neuro-plastic changes in exogenous (input-driven) and endogenous (attention-dependent) components of auditory event-related potentials (ERPs). Evidence suggests that musicians, compared to non-musicians, experience less age-related decline in auditory processing abilities. Here, we investigated whether lifelong musicianship mitigates exogenous or endogenous processing by measuring auditory ERPs in younger and older musicians and non-musicians while they either attended to auditory stimuli or watched a muted subtitled movie of their choice. Both age and musical training-related differences were observed in the exogenous components; however, the differences between musicians and non-musicians were similar across the lifespan. These results suggest that exogenous auditory ERPs are enhanced in musicians, but decline with age at the same rate. On the other hand, attention-related activity, modeled in the right auditory cortex using a discrete spatiotemporal source analysis, was selectively enhanced in older musicians. This suggests that older musicians use a compensatory strategy to overcome age-related decline in peripheral and exogenous processing of acoustic information. Copyright © 2014 Elsevier Inc. All rights reserved.

SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

PubMed

Mason, Paul; Liang, Beirong; Li, Lingyun; Fremgen, Trisha; Murphy, Erin; Quinn, Angela; Madden, Stephen L; Biemann, Hans-Peter; Wang, Bing; Cohen, Aharon; Komarnitsky, Svetlana; Jancsics, Kate; Hirth, Brad; Cooper, Christopher G F; Lee, Edward; Wilson, Sean; Krumbholz, Roy; Schmid, Steven; Xiang, Yibin; Booker, Michael; Lillie, James; Carter, Kara

2012-01-01

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway.

Probing Protein Sequences as Sources for Encrypted Antimicrobial Peptides

PubMed Central

Brand, Guilherme D.; Magalhães, Mariana T. Q.; Tinoco, Maria L. P.; Aragão, Francisco J. L.; Nicoli, Jacques; Kelly, Sharon M.; Cooper, Alan; Bloch, Carlos

2012-01-01

Starting from the premise that a wealth of potentially biologically active peptides may lurk within proteins, we describe here a methodology to identify putative antimicrobial peptides encrypted in protein sequences. Candidate peptides were identified using a new screening procedure based on physicochemical criteria to reveal matching peptides within protein databases. Fifteen such peptides, along with a range of natural antimicrobial peptides, were examined using DSC and CD to characterize their interaction with phospholipid membranes. Principal component analysis of DSC data shows that the investigated peptides group according to their effects on the main phase transition of phospholipid vesicles, and that these effects correlate both to antimicrobial activity and to the changes in peptide secondary structure. Consequently, we have been able to identify novel antimicrobial peptides from larger proteins not hitherto associated with such activity, mimicking endogenous and/or exogenous microorganism enzymatic processing of parent proteins to smaller bioactive molecules. A biotechnological application for this methodology is explored. Soybean (Glycine max) plants, transformed to include a putative antimicrobial protein fragment encoded in its own genome were tested for tolerance against Phakopsora pachyrhizi, the causative agent of the Asian soybean rust. This procedure may represent an inventive alternative to the transgenic technology, since the genetic material to be used belongs to the host organism and not to exogenous sources. PMID:23029273

Modeling water exchange and contaminant transport through a Baltic coastal region.

PubMed

Engqvist, Anders; Döös, Kristofer; Andrejev, Oleg

2006-12-01

The water exchange of the Baltic coastal zone is characterized by its seasonally varying regimes. In the safety assessment of a potential repository for spent nuclear fuel, it is important to assess the consequences of a hypothetical leak of radionuclides through the seabed into a waterborne transport phase. In particular, estimates of the associated residence times in the near-shore coastal zone are of interest. There are several methods to quantify such measures, of which three are presented here. Using the coastal location of Forsmark (Sweden) as an example, methods based on passive tracers, particle trajectories, and the average age distribution of exogeneous water parcels are compared for a representative one-year cycle. Tracer-based methods can simulate diffusivity more realistically than the other methods. Trajectory-based methods can handle Lagrangian dispersion processes due to advection but neglect diffusion on the sub-grid scale. The method based on the concept of average age (AvA) of exogeneous water can include all such sources simultaneously not only boundary water bodies but also various (fresh)-water discharges. Due to the inclusion of sub-grid diffusion this method gives a smoother measure of the water renewal. It is shown that backward in time trajectories and AvA-times are basically equipollent methods, yielding correlated results within the limits set by the diffusivity.

Effect of exogenous metal ions and mechanical stress on rice processed in thermal-solid enzymatic reaction system related to further alcoholic fermentation efficiency.

PubMed

Xu, Enbo; Wu, Zhengzong; Jiao, Aiquan; Jin, Zhengyu

2018-02-01

Metal-rich thermal-solid enzymatic processing of rice combined with yeast fermentation was investigated. 8 Metal ions were exogenously supplied at 0.05, 0.5 and 5mmol/100g (MG) rice prior to static high pressure enzymatic cooking (HPEC) and dynamic enzymatic extrusion cooking (EEC). Treated rice and its fermentation efficiency (FE) were characterized by rapid viscosity analyzer (RVA), UV-Vis, FT-IR and atomic absorption spectrophotometer (AAS). The optimum pH range of enzyme in solid system (>4.9) was broader than in a liquid system (>5.5). Cations decreased enzymatic activity in HPEC probably due to metal-induced aggregation of rice matrix with reduced reacting area as well as strengthened structure of starch/polysaccharides modified by metals. While using the EEC with mechanical mixing/shearing, relative activity was activated to 110 and 120% by Mg 2+ (0.05-0.5MG) and Ca 2+ (0.05-5MG), respectively. Furthermore, the effectiveness of residual ions to promote further FE was found to follow the order: Ca 2+ >K + >Zn 2+ >Mg 2+ >Mn 2+ >Na + ≈Control>Fe 2+ >Cu 2+ , individually. Copyright © 2017 Elsevier Ltd. All rights reserved.

The GDNF Target Vsnl1 Marks the Ureteric Tip

PubMed Central

Ola, Roxana; Jakobson, Madis; Kvist, Jouni; Perälä, Nina; Kuure, Satu; Braunewell, Karl-Heinz; Bridgewater, Darren; Rosenblum, Norman D.; Chilov, Dmitri; Immonen, Tiina; Sainio, Kirsi

2011-01-01

Glial cell line-derived neurotrophic factor (GDNF) is indispensable for ureteric budding and branching. If applied exogenously, GDNF promotes ectopic ureteric buds from the Wolffian duct. Although several downstream effectors of GDNF are known, the identification of early response genes is incomplete. Here, microarray screening detected several GDNF-regulated genes in the Wolffian duct, including Visinin like 1 (Vsnl1), which encodes a neuronal calcium-sensor protein. We observed renal Vsnl1 expression exclusively in the ureteric epithelium, but not in Gdnf-null kidneys. In the tissue culture of Gdnf-deficient kidney primordium, exogenous GDNF and alternative bud inducers (FGF7 and follistatin) restored Vsnl1 expression. Hence, Vsnl1 characterizes the tip of the ureteric bud epithelium regardless of the inducer. In the tips, Vsnl1 showed a mosaic expression pattern that was mutually exclusive with β-catenin transcriptional activation. Vsnl1 was downregulated in both β-catenin-stabilized and β-catenin-deficient kidneys. Moreover, in a mouse collecting duct cell line, Vsnl1 compromised β-catenin stability, suggesting a counteracting relationship between Vsnl1 and β-catenin. In summary, Vsnl1 marks ureteric bud tips in embryonic kidneys, and its mosaic pattern demonstrates a heterogeneity of cell types that may be critical for normal ureteric branching. PMID:21289216

A new model for the characterization of infection risk in gunshot injuries:Technology, principal consideration and clinical implementation

PubMed Central

2011-01-01

Introduction The extent of wound contamination in gunshot injuries is still a topic of controversial debate. The purpose of the present study is to develop a model that illustrates the contamination of wounds with exogenous particles along the bullet path. Material and methods To simulate bacteria, radio-opaque barium titanate (3-6 μm in diameter) was atomized in a dust chamber. Full metal jacket or soft point bullets caliber .222 (n = 12, v0 = 1096 m/s) were fired through the chamber into a gelatin block directly behind it. After that, the gelatin block underwent multi-slice CT in order to analyze the permanent and temporary wound cavity. Results The permanent cavity caused by both types of projectiles showed deposits of barium titanate distributed over the entire bullet path. Full metal jacket bullets left only few traces of barium titanate in the temporary cavity. In contrast, the soft point bullets disintegrated completely, and barium titanate covered the entire wound cavity. Discussion Deep penetration of potential exogenous bacteria can be simulated easily and reproducibly with barium titanate particles shot into a gelatin block. Additionally, this procedure permits conclusions to be drawn about the distribution of possible contaminants and thus can yield essential findings in terms of necessary therapeutic procedures. PMID:22032229

Differential Effects of Hormones on Cellular Metabolism in Keratoconus In Vitro

PubMed Central

McKay, Tina B.; Hjortdal, Jesper; Sejersen, Henrik; Karamichos, Dimitrios

2017-01-01

Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs). Our data showed that exogenous DHEA significantly downregulated IGF-1 and its receptor in both HCFs and HKCs with HKCs showing consistently lower basal pentose phosphate flux. Prolactin caused no significant change in IGF-1 levels and an increase in IGF-2 in HKCs correlating with an increase in ATP and NADH levels. 17β-estradiol led to a significant upregulation in pentose phosphate flux and glycolytic intermediates in HCFs. Our results identified hormone-specific responses regulated in HKCs compared to HCFs revealing a novel role for hormones on bioenergetics in KC. PMID:28211546

Uncovering DELLA-Independent Gibberellin Responses by Characterizing New Tomato procera Mutants

PubMed Central

Livne, Sivan; Lor, Vai S.; Nir, Ido; Eliaz, Natanella; Aharoni, Asaph; Olszewski, Neil E.; Eshed, Yuval; Weiss, David

2015-01-01

Gibberellin (GA) regulates plant development primarily by triggering the degradation/deactivation of the DELLA proteins. However, it remains unclear whether all GA responses are regulated by DELLAs. Tomato (Solanum lycopersicum) has a single DELLA gene named PROCERA (PRO), and its recessive pro allele exhibits constitutive GA activity but retains responsiveness to external GA. In the loss-of-function mutant proΔGRAS, all examined GA developmental responses were considerably enhanced relative to pro and a defect in seed desiccation tolerance was uncovered. As pro, but not proΔGRAS, elongation was promoted by GA treatment, pro may retain residual DELLA activity. In agreement with homeostatic feedback regulation of the GA biosynthetic pathway, we found that GA20oxidase1 expression was suppressed in proΔGRAS and was not affected by exogenous GA3. In contrast, expression of GA2oxidase4 was not affected by the elevated GA signaling in proΔGRAS but was strongly induced by exogenous GA3. Since a similar response was found in Arabidopsis thaliana plants with impaired activity of all five DELLA genes, we suggest that homeostatic GA responses are regulated by both DELLA-dependent and -independent pathways. Transcriptome analysis of GA-treated proΔGRAS leaves suggests that 5% of all GA-regulated genes in tomato are DELLA independent. PMID:26036254

Cassini-CDA Science in 2014 and beyond

NASA Astrophysics Data System (ADS)

Srama, Ralf

2015-04-01

Today, the German-lead Cosmic Dust Analyser (CDA) is operated continuously for 10 years in orbit around Saturn. Many discoveries like the Saturn nanodust streams or the large extended E-ring were achieved. CDA provided unique results regarding Enceladus, his plume and the liquid water below the icy crust. In 2014 and 2015 CDA focuses on extended inclination and equatorial scans of the ring particle densities. Furthermore, scans are performed of the Pallene and Helene regions. Special attention is also given to the search of the dust cloud around Dione and to the Titan region. Long integration times are needed in order to characterize the flux and composition of exogenous dust (including interstellar dust) or possible retrograde dust particles. Finally, dedicated observation campaigns focus on the coupling of nanodust streams to Saturn's magnetosphere and the search of possible periodicities in the stream data. Saturn's rotation frequency was identified in the impact rate of nanodust particles at a Saturn distance of 40 Saturn radii. In the final three years CDA performs exogenous and interstellar dust campaigns, studies of the composition and origin of Saturn's main rings by unique ring ejecta measurements, long-duration nano-dust stream observations, high-resolution maps of small moon orbit crossings, studies of the dust cloud around Dione and studies of the E-ring interaction with the large moon Titan.

Malate-aspartate shuttle and exogenous NADH/cytochrome c electron transport pathway as two independent cytosolic reducing equivalent transfer systems.

PubMed

Abbrescia, Daniela Isabel; La Piana, Gianluigi; Lofrumento, Nicola Elio

2012-02-15

In mammalian cells aerobic oxidation of glucose requires reducing equivalents produced in glycolytic phase to be channelled into the phosphorylating respiratory chain for the reduction of molecular oxygen. Data never presented before show that the oxidation rate of exogenous NADH supported by the malate-aspartate shuttle system (reconstituted in vitro with isolated liver mitochondria) is comparable to the rate obtained on activation of the cytosolic NADH/cytochrome c electron transport pathway. The activities of these two reducing equivalent transport systems are independent of each other and additive. NADH oxidation induced by the malate-aspartate shuttle is inhibited by aminooxyacetate and by rotenone and/or antimycin A, two inhibitors of the respiratory chain, while the NADH/cytochrome c system remains insensitive to all of them. The two systems may simultaneously or mutually operate in the transfer of reducing equivalents from the cytosol to inside the mitochondria. In previous reports we suggested that the NADH/cytochrome c system is expected to be functioning in apoptotic cells characterized by the presence of cytochrome c in the cytosol. As additional new finding the activity of reconstituted shuttle system is linked to the amount of α-ketoglutarate generated inside the mitochondria by glutamate dehydrogenase rather than by aspartate aminotransferase. Copyright © 2011 Elsevier Inc. All rights reserved.

Hypochlorous acid regulates neutrophil extracellular trap release in humans

PubMed Central

Palmer, L J; Cooper, P R; Ling, M R; Wright, H J; Huissoon, A; Chapple, I L C

2012-01-01

Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine. PMID:22236002

Identification of Genomic Insertion and Flanking Sequence of G2-EPSPS and GAT Transgenes in Soybean Using Whole Genome Sequencing Method.

PubMed

Guo, Bingfu; Guo, Yong; Hong, Huilong; Qiu, Li-Juan

2016-01-01

Molecular characterization of sequence flanking exogenous fragment insertion is essential for safety assessment and labeling of genetically modified organism (GMO). In this study, the T-DNA insertion sites and flanking sequences were identified in two newly developed transgenic glyphosate-tolerant soybeans GE-J16 and ZH10-6 based on whole genome sequencing (WGS) method. More than 22.4 Gb sequence data (∼21 × coverage) for each line was generated on Illumina HiSeq 2500 platform. The junction reads mapped to boundaries of T-DNA and flanking sequences in these two events were identified by comparing all sequencing reads with soybean reference genome and sequence of transgenic vector. The putative insertion loci and flanking sequences were further confirmed by PCR amplification, Sanger sequencing, and co-segregation analysis. All these analyses supported that exogenous T-DNA fragments were integrated in positions of Chr19: 50543767-50543792 and Chr17: 7980527-7980541 in these two transgenic lines. Identification of genomic insertion sites of G2-EPSPS and GAT transgenes will facilitate the utilization of their glyphosate-tolerant traits in soybean breeding program. These results also demonstrated that WGS was a cost-effective and rapid method for identifying sites of T-DNA insertions and flanking sequences in soybean.

Early Induction of Apple Fruitlet Abscission Is Characterized by an Increase of Both Isoprene Emission and Abscisic Acid Content12[W][OA

PubMed Central

Giulia, Eccher; Alessandro, Botton; Mariano, Dimauro; Andrea, Boschetti; Benedetto, Ruperti; Angelo, Ramina

2013-01-01

Apple (Malus domestica) fruitlet abscission represents an interesting model system to study the early phases of the shedding process, during which major transcriptomic changes and metabolic rearrangements occur within the fruit. In apple, the drop of fruits at different positions within the cluster can be selectively magnified through chemical thinners, such as benzyladenine and metamitron, acting as abscission enhancers. In this study, different abscission potentials were obtained within the apple fruitlet population by means of the above-cited thinners. A metabolomic study was conducted on the volatile organic compounds emitted by abscising fruitlets, allowing for identification of isoprene as an early marker of abscission induction. A strong correlation was also observed between isoprene production and abscisic acid (ABA) levels in the fruit cortex, which were shown to increase in abscising fruitlets with respect to nonabscising ones. Transcriptomic evidence indicated that abscission-related ABA is biologically active, and its increased biosynthesis is associated with the induction of a specific ABA-responsive 9-cis-epoxycarotenoid dioxygenase gene. According to a hypothetical model, ABA may transiently cooperate with other hormones and secondary messengers in the generation of an intrafruit signal leading to the downstream activation of the abscission zone. The shedding process therefore appears to be triggered by multiple interdependent pathways, whose fine regulation, exerted within a very short temporal window by both endogenous and exogenous factors, determines the final destiny of the fruitlets. PMID:23444344

Cytochrome P450s--Their expression, regulation, and role in insecticide resistance.

PubMed

Liu, Nannan; Li, Ming; Gong, Youhui; Liu, Feng; Li, Ting

2015-05-01

P450s are known to be critical for the detoxification and/or activation of xenobiotics such as drugs and pesticides and overexpression of P450 genes can significantly affect the disposition of xenobiotics in the tissues of organisms, altering their pharmacological/toxicological effects. In insects, P450s play an important role in detoxifying exogenous compounds such as insecticides and plant toxins and their overexpression can result in increased levels of P450 proteins and P450 activities. This has been associated with enhanced metabolic detoxification of insecticides and has been implicated in the development of insecticide resistance in insects. Multiple P450 genes have been found to be co-overexpressed in individual insect species via several constitutive overexpression and induction mechanisms, which in turn are co-responsible for high levels of insecticide resistance. Many studies have also demonstrated that the transcriptional overexpression of P450 genes in resistant insects is regulated by trans and/or cis regulatory genes/factors. Taken together, these earlier findings suggest not only that insecticide resistance is conferred via multi-resistance P450 genes, but also that it is mediated through the interaction of regulatory genes/factors and resistance genes. This chapter reviews our current understanding of how the molecular mechanisms of P450 interaction/gene regulation govern the development of insecticide resistance in insects and our progress along the road to a comprehensive characterization of P450 detoxification-mediated insecticide resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmental chemical exposures and disturbances of heme synthesis.

PubMed Central

Daniell, W E; Stockbridge, H L; Labbe, R F; Woods, J S; Anderson, K E; Bissell, D M; Bloomer, J R; Ellefson, R D; Moore, M R; Pierach, C A; Schreiber, W E; Tefferi, A; Franklin, G M

1997-01-01

Porphyrias are relatively uncommon inherited or acquired disorders in which clinical manifestations are attributable to a disturbance of heme synthesis (porphyrin metabolism), usually in association with endogenous or exogenous stressors. Porphyrias are characterized by elevations of heme precursors in blood, urine, and/or stool. A number of chemicals, particularly metals and halogenated hydrocarbons, induce disturbances of heme synthesis in experimental animals. Certain chemicals have also been linked to porphyria or porphyrinuria in humans, generally involving chronic industrial exposures or environmental exposures much higher than those usually encountered. A noteworthy example is the Turkish epidemic of porphyria cutanea tarda produced by accidental ingestion of wheat treated with the fungicide hexachlorobenzene. Measurements of excreted heme precursors have the potential to serve as biological markers for harmful but preclinical effects of certain chemical exposures; this potential warrants further research and applied field studies. It has been hypothesized that several otherwise unexplained chemical-associated illnesses, such as multiple chemical sensitivity syndrome, may represent mild chronic cases of porphyria or other acquired abnormalities in heme synthesis. This review concludes that, although it is reasonable to consider such hypotheses, there is currently no convincing evidence that these illnesses are mediated by a disturbance of heme synthesis; it is premature or unfounded to base clinical management on such explanations unless laboratory data are diagnostic for porphyria. This review discusses the limitations of laboratory measures of heme synthesis, and diagnostic guidelines are provided to assist in evaluating the symptomatic individual suspected of having a porphyria. PMID:9114276

Developmental estrogen exposures and disruptions to maternal behavior and brain: Effects of ethinyl estradiol, a common positive control.

PubMed

Catanese, Mary C; Vandenberg, Laura N

2017-11-07

Due of its structural similarity to the endogenous estrogen 17β-estradiol (E2), the synthetic estrogen 17α-ethinyl estradiol (EE2) is widely used to study the effects of estrogenic substances on sensitive organs at multiple stages of development. Here, we investigated the effects of EE2 on maternal behavior and the maternal brain in females exposed during gestation and the perinatal period. We assessed several components of maternal behavior including nesting behavior and pup retrieval; characterized the expression of estrogen receptor (ER)α in the medial preoptic area (MPOA), a brain region critical for the display of maternal behavior; and measured expression of tyrosine hydroxylase, a marker for dopaminergic cells, in the ventral tegmental area (VTA), a brain region important in maternal motivation. We found that developmental exposure to EE2 induces subtle effects on several aspects of maternal behavior including time building the nest and time spent engaged in self-care. Developmental exposure to EE2 also altered ERα expression in the central MPOA during both early and late lactation and led to significantly reduced tyrosine hydroxylase immunoreactivity in the VTA. Our results demonstrate both dose- and postpartum stage-related effects of developmental exposure to EE2 on behavior and brain that manifest later in adulthood, during the maternal period. These findings provide further evidence for effects of exposure to exogenous estrogenic compounds during the critical periods of fetal and perinatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Nutrients in folate-mediated, one-carbon metabolism and risk of rectal tumors in men and women

PubMed Central

Curtin, Karen; Samowitz, Wade S.; Ulrich, Cornelia M.; Wolff, Roger K.; Herrick, Jennifer S; Caan, Bette J.; Slattery, Martha L.

2011-01-01

In an investigation of rectal tumors characterized by CpG Island Methylator Phenotype (CIMP), KRAS2 mutation, and TP53 mutation, we examined associations with dietary and supplemental folate, riboflavin, vitamins B6 andB12, and methionine, nutrients involved in folate-mediated one-carbon metabolism. We also examined folate intake and common MTHFR polymorphisms in relation to CIMP. Data from a population-based study of 951 cases (750 with tumor markers) and 1,205 controls were evaluated using multiple logistic regression models and generalized estimating equations. Reduced risk of methylated tumors was suggested in women with upper tertiles of folate intake (≥0.42 mg/day) vs. lower tertile: OR=0.6, 95%CI 0.3–1.2. In men, a significant 3-fold increased risk of CIMP+ tumor was observed for the upper tertile of folate (≥0.75 mg/day) vs. the lower tertile (<0.44 mg/day): OR=3.2, 95%CI 1.5–6.7. These men consumed a greater proportion of folic-acid fortified foods relative to natural, primarily plant-based sources (52% vs. 48%) than women with CIMP+ tumor (22% vs. 78%). MTHFR 1298A>C influenced folate in male CIMP+ risk (P-interaction<0.01). Our findings suggest folate supplementation effects may differ between genders, perhaps due to variation in MTHFR and/or endogenous/exogenous hormones, and may be important in the initiation and progression of methylated rectal tumors in men. PMID:21462086

MRP4/ABCC4 as a new therapeutic target: meta-analysis to determine cAMP binding sites as a tool for drug design.

PubMed

Yaneff, Agustín; Sahores, Ana; Gomez, Natalia; Carozzo, Alejandro; Shayo, Carina; Davio, Carlos

2017-12-29

MRP4 transports multiple endogenous and exogenous substances and is critical not only for detoxification but also in the homeostasis of several signaling molecules. Its dysregulation has been reported in numerous pathological disorders, thus MRP4 appears as an attractive therapeutic target. However, the efficacy of MRP4 inhibitors is still controversial. The design of specific pharmacological agents with the ability to selectively modulate the activity of this transporter or modify its affinity to certain substrates represents a challenge in current medicine and chemical biology. The first step in the long process of drug rational design is to identify the therapeutic target and characterize the mechanism by which it affects the given pathology. In order to develop a pharmacological agent with high specific activity, the second step is to systematically study the structure of the target and identify all the possible binding sites. Using available homology models and mutagenesis assays, in this review we recapitulate the up-to-date knowledge about MRP structure and aligned amino acid sequences to identify the candidate MRP4 residues where cyclic nucleotides bind. We have also listed the most relevant MRP inhibitors studied to date, considering drug safety and specificity for MRP4 in particular. This metaanalysis platform may serve as a basis for the future development of inhibitors of MRP4 cAMP specific transport. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Laron syndrome: Presentation, treatment and prognosis].

PubMed

Latrech, Hanane; Polak, Michel

2016-01-01

Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Methods to Enhance Laser Speckle Imaging of High-Flow and Low-Flow Vasculature

PubMed Central

Choi, Bernard; Ringold, Tyson L.; Kim, Jeehyun

2012-01-01

The objective of this paper is to present two methods to extend the response range of laser speckle imaging (LSI). We report on the use of two methods (image exposure time control and magnetomotive actuation of exogenous contrast agents) to enhance characterization of high- and low-flow vasculature, respectively. With an exposure time of 10 and 0.01 ms, the linear response range extended to 10 and 280 mm/s, respectively. With application of an AC magnetic field to a solution of stagnant SPIO particles, an apparent increase of ~3× in speckle flow index was induced. PMID:19964103

A gyrovirus infecting a sea bird

PubMed Central

Li, Linlin; Pesavento, Patricia A.; Gaynor, Anne M.; Duerr, Rebecca S.; Phan, Tung Gia; Zhang, Wen; Deng, Xutao

2015-01-01

We characterized the genome of a highly divergent gyrovirus (GyV8) in the spleen and uropygial gland tissues of a diseased northern fulmar (Fulmarus glacialis), a pelagic bird beached in San Francisco, California. No other exogenous viral sequences could be identified using viral metagenomics. The small circular DNA genome shared no significant nucleotide sequence identity, and only 38–42 % amino acid sequence identity in VP1, with any of the previously identified gyroviruses. GyV8 is the first member of the third major phylogenetic clade of this viral genus and the first gyrovirus detected in an avian species other than chicken. PMID:26036564

Robust consensus algorithm for multi-agent systems with exogenous disturbances under convergence conditions

NASA Astrophysics Data System (ADS)

Jiang, Yulian; Liu, Jianchang; Tan, Shubin; Ming, Pingsong

2014-09-01

In this paper, a robust consensus algorithm is developed and sufficient conditions for convergence to consensus are proposed for a multi-agent system (MAS) with exogenous disturbances subject to partial information. By utilizing H∞ robust control, differential game theory and a design-based approach, the consensus problem of the MAS with exogenous bounded interference is resolved and the disturbances are restrained, simultaneously. Attention is focused on designing an H∞ robust controller (the robust consensus algorithm) based on minimisation of our proposed rational and individual cost functions according to goals of the MAS. Furthermore, sufficient conditions for convergence of the robust consensus algorithm are given. An example is employed to demonstrate that our results are effective and more capable to restrain exogenous disturbances than the existing literature.

Acute exogenous lipoid pneumonia caused by accidental kerosene ingestion in an elderly patient with dementia: a case report.

PubMed

Gotanda, Hiroshi; Kameyama, Yumi; Yamaguchi, Yasuhiro; Ishii, Masaki; Hanaoka, Yoko; Yamamoto, Hiroshi; Ogawa, Sumito; Iijima, Katsuya; Akishita, Masahiro; Ouchi, Yasuyoshi

2013-01-01

Acute exogenous lipoid pneumonia is an uncommon condition caused by aspiration of oil-based substances, occurring mainly in children. Here, we report the case of an 83-year-old patient with Alzheimer's disease who presented with coughing and hypoxia. The diagnosis of acute exogenous lipoid pneumonia caused by accidental kerosene ingestion was made on the basis of the patient's clinical history, and typical radiological and cytological findings. The patient's cognitive impairment and an unsafe environment, in which the patient's 91-year-old husband stored kerosene in an old shochu bottle, were responsible for the accidental ingestion. Acute exogenous lipoid pneumonia should be considered in the differential diagnosis for acute respiratory disorders in the rapidly aging population. © 2013 Japan Geriatrics Society.

Effect of endotoxin and radio-detoxified endotoxin on the serum T4 level of rats and response of their thyroid gland to exogenous TSH

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

Bertok, L.; Nagy, S.U.

Experiments were performed to demonstrate that, while the shock-inducing dose of parent (toxic) endotoxin significantly decreases the serum T4 level of rats and inhibits the T4 response given to exogenous thyroid stimulating hormone (TSH), the radio-detoxified (/sup 60/Co-gamma, 150 kGy) endotoxin preparation does not inhibit the response to exogenous TSH. It also decreases serum T4 level to a lesser extent than untreated endotoxin.

Defective B cell response to T-dependent immunization in lupus-prone mice

PubMed Central

Niu, Haitao; Sobel, Eric S.; Morel, Laurence

2009-01-01

Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

Super-resolution atomic force photoactivated microscopy of biological samples (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Kim, Hyemin; Shin, Seungjun; Doh, Junsang; Kim, Chulhong

2017-03-01

Optical microscopy (OM) and photoacoustic microscopy (PAM) have previously been used to image the optical absorption of intercellular features of biological cells. However, the optical diffraction limit ( 200 nm) makes it difficult for these modalities to image nanoscale inner cell structures and the distribution of internal cell components. Although super-resolution fluorescence microscopy, such as stimulated emission depletion microscopy (STED) and stochastic optical reconstruction microscopy (STORM), has successfully performed nanoscale biological imaging, these modalities require the use of exogenous fluorescence agents, which are unfavorable for biological samples. Our newly developed atomic force photoactivated microscopy (AFPM) can provide optical absorption images with nanoscale lateral resolution without any exogenous contrast agents. AFPM combines conventional atomic force microscopy (AFM) and an optical excitation system, and simultaneously provides multiple contrasts, such as the topography and magnitude of optical absorption. AFPM can detect the intrinsic optical absorption of samples with 8 nm lateral resolution, easily overcoming the diffraction limit. Using the label-free AFPM system, we have successfully imaged the optical absorption properties of a single melanoma cell (B16F10) and a rosette leaf epidermal cell of Arabidopsis (ecotype Columbia (Col-0)) with nanoscale lateral resolution. The remarkable images show the melanosome distribution of a melanoma cell and the biological structures of a plant cell. AFPM provides superior imaging of optical absorption with a nanoscale lateral resolution, and it promises to become widely used in biological and chemical research.

Resistance to BmNPV via Overexpression of an Exogenous Gene Controlled by an Inducible Promoter and Enhancer in Transgenic Silkworm, Bombyx mori

PubMed Central

Jiang, Liang; Cheng, Tingcai; Zhao, Ping; Yang, Qiong; Wang, Genhong; Jin, Shengkai; Lin, Ping; Xiao, Yang; Xia, Qingyou

2012-01-01

The hycu-ep32 gene of Hyphantria cunea NPV can inhibit Bombyx mori nucleopolyhedrovirus (BmNPV) multiplication in co-infected cells, but it is not known whether the overexpression of the hycu-ep32 gene has an antiviral effect in the silkworm, Bombyx mori. Thus, we constructed four transgenic vectors, which were under the control of the 39 K promoter of BmNPV (39 KP), Bombyx mori A4 promoter (A4P), hr3 enhancer of BmNPV combined with 39 KP, and hr3 combined with A4P. Transgenic lines were created via embryo microinjection using practical diapause silkworm. qPCR revealed that the expression level of hycu-ep32 could be induced effectively after BmNPV infection in transgenic lines where hycu-ep32 was controlled by hr3 combined with 39 KP (i.e., HEKG). After oral inoculation of BmNPV with 3 × 105 occlusion bodies per third instar, the mortality with HEKG-B was approximately 30% lower compared with the non-transgenic line. The economic characteristics of the transgenic lines remained unchanged. These results suggest that overexpression of an exogenous antiviral gene controlled by an inducible promoter and enhancer is a feasible method for breeding silkworms with a high antiviral capacity. PMID:22870254

Identification of a novel splice variant isoform of TREM-1 in human neutrophil granules1

PubMed Central

Baruah, Sankar; Keck, Kathy; Vrenios, Michelle; Pope, Marshall; Pearl, Merideth; Doerschug, Kevin; Klesney-Tait, Julia

2015-01-01

Triggering receptor expressed on myeloid cells-1 (TREM-1) is critical for inflammatory signal amplification. Humans have two forms of TREM-1: a membrane receptor (mbTREM-1), associated with the adaptor DAP12, and a soluble receptor detected at times of infection. The membrane receptor isoform acts synergistically with the TLR pathway to promote cytokine secretion and neutrophil migration while the soluble receptor functions as a counter regulatory molecule. In multiple models of sepsis, exogenous administration of soluble forms of TREM-1 attenuates inflammation and markedly improves survival. Despite intense interest in soluble TREM-1 both as a clinical predictor of survival and as a therapeutic tool, the origin of native soluble TREM-1 remains controversial. Utilizing human neutrophils, we identified a 15 kDa TREM-1 isoform in primary (azurophilic) and secondary (specific) granules. Mass spectrometric analysis, ELISA, and immunoblot confirm that the 15 kD protein is a novel splice variant of TREM-1 (TREM-1sv). Neutrophil stimulation with P. aeruginosa, LPS, or PAM(3)Cys4 resulted in degranulation and release of TREM-1sv. The addition of exogenous TREM-1sv inhibited TREM-1 receptor mediated proinflammatory cytokine production. Thus these data reveal that TREM-1 isoforms simultaneously activate and inhibit inflammation via the canonical membrane TREM-1 molecule and this newly discovered granular isoform, TREM-1sv. PMID:26561551

Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.

PubMed

Baruah, Sankar; Keck, Kathy; Vrenios, Michelle; Pope, Marshall R; Pearl, Merideth; Doerschug, Kevin; Klesney-Tait, Julia

2015-12-15

Triggering receptor expressed on myeloid cells-1 (TREM-1) is critical for inflammatory signal amplification. Humans have two forms of TREM-1: a membrane receptor, associated with the adaptor DAP12, and a soluble receptor detected at times of infection. The membrane receptor isoform acts synergistically with the TLR pathway to promote cytokine secretion and neutrophil migration, whereas the soluble receptor functions as a counterregulatory molecule. In multiple models of sepsis, exogenous administration of soluble forms of TREM-1 attenuates inflammation and markedly improves survival. Despite intense interest in soluble TREM-1, both as a clinical predictor of survival and as a therapeutic tool, the origin of native soluble TREM-1 remains controversial. Using human neutrophils, we identified a 15-kDa TREM-1 isoform in primary (azurophilic) and secondary (specific) granules. Mass spectrometric analysis, ELISA, and immunoblot confirm that the 15-kDa protein is a novel splice variant form of TREM-1 (TREM-1sv). Neutrophil stimulation with Pseudomonas aeruginosa, LPS, or PAM(3)Cys4 resulted in degranulation and release of TREM-1sv. The addition of exogenous TREM-1sv inhibited TREM-1 receptor-mediated proinflammatory cytokine production. Thus, these data reveal that TREM-1 isoforms simultaneously activate and inhibit inflammation via the canonical membrane TREM-1 molecule and this newly discovered granular isoform, TREM-1sv. Copyright © 2015 by The American Association of Immunologists, Inc.

Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya.

PubMed

Hilker, Frank M; Allen, Linda J S; Bokil, Vrushali A; Briggs, Cheryl J; Feng, Zhilan; Garrett, Karen A; Gross, Louis J; Hamelin, Frédéric M; Jeger, Michael J; Manore, Carrie A; Power, Alison G; Redinbaugh, Margaret G; Rúa, Megan A; Cunniffe, Nik J

2017-10-01

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

The effects of exogenous cortisol on myostatin transcription in rainbow trout, Oncorhynchus mykiss

PubMed Central

Galt, Nicholas J.; Froehlich, Jacob Michael; Remily, Ethan A.; Romero, Sinibaldo R.; Biga, Peggy R.

2014-01-01

Glucocorticoids (GCs) strongly regulate myostatin transcript levels in mammals via glucocorticoid response elements (GREs) in the myostatin promoter, and bioinformatics methods suggest that this regulatory mechanism is conserved among many vertebrates. However, the multiple myostatin genes found in some fishes may be an exception. In rainbow trout (Oncorhynchus mykiss), two genome duplication events have produced three putatively functional myostatin genes, myostatin-1a, -1b and -2a, which are ubiquitously and differentially expressed. In addition, in silico promoter analyses of the rainbow trout myostatin promoters have failed to identify putative GREs, suggesting a divergence in myostatin function. Therefore, we hypothesized that myostatin mRNA expression is not regulated by glucocorticoids in rainbow trout. In this study, both juvenile rainbow trout and primary trout myoblasts were treated with cortisol to examine the relationship between this glucocorticoid and myostatin mRNA expression. Results suggest that exogenous cortisol does not regulate myostatin-1a and -1b expression in vivo, as myostatin mRNA levels were not significantly affected by cortisol treatment in either red or white muscle tissue. In red muscle, myostatin-2a levels were significantly elevated in the cortisol treatment group relative to the control, but not the vehicle control, at both 12 h and 24 h post-injection. As such, it is unclear if cortisol was acting alone or in combination with the vehicle. Cortisol increased myostatin-1b expression in a dose-dependent manner in vitro. Further work is needed to determine if this response is the direct result of cortisol acting on the myostatin-1b promoter or through an alternative mechanism. These results suggest that regulation of myostatin by cortisol may not be as highly conserved as previously thought and support previous work that describes potential functional divergence of the multiple myostatin genes in fishes. PMID:24875565

Development of one novel multiple-target plasmid for duplex quantitative PCR analysis of roundup ready soybean.

PubMed

Zhang, Haibo; Yang, Litao; Guo, Jinchao; Li, Xiang; Jiang, Lingxi; Zhang, Dabing

2008-07-23

To enforce the labeling regulations of genetically modified organisms (GMOs), the application of reference molecules as calibrators is becoming essential for practical quantification of GMOs. However, the reported reference molecules with tandem marker multiple targets have been proved not suitable for duplex PCR analysis. In this study, we developed one unique plasmid molecule based on one pMD-18T vector with three exogenous target DNA fragments of Roundup Ready soybean GTS 40-3-2 (RRS), that is, CaMV35S, NOS, and RRS event fragments, plus one fragment of soybean endogenous Lectin gene. This Lectin gene fragment was separated from the three exogenous target DNA fragments of RRS by inserting one 2.6 kb DNA fragment with no relatedness to RRS detection targets in this resultant plasmid. Then, we proved that this design allows the quantification of RRS using the three duplex real-time PCR assays targeting CaMV35S, NOS, and RRS events employing this reference molecule as the calibrator. In these duplex PCR assays, the limits of detection (LOD) and quantification (LOQ) were 10 and 50 copies, respectively. For the quantitative analysis of practical RRS samples, the results of accuracy and precision were similar to those of simplex PCR assays, for instance, the quantitative results were at the 1% level, the mean bias of the simplex and duplex PCR were 4.0% and 4.6%, respectively, and the statistic analysis ( t-test) showed that the quantitative data from duplex and simplex PCR had no significant discrepancy for each soybean sample. Obviously, duplex PCR analysis has the advantages of saving the costs of PCR reaction and reducing the experimental errors in simplex PCR testing. The strategy reported in the present study will be helpful for the development of new reference molecules suitable for duplex PCR quantitative assays of GMOs.

A genomics approach to understanding the role of auxin in apple (Malus x domestica) fruit size control.

PubMed

Devoghalaere, Fanny; Doucen, Thomas; Guitton, Baptiste; Keeling, Jeannette; Payne, Wendy; Ling, Toby John; Ross, John James; Hallett, Ian Charles; Gunaseelan, Kularajathevan; Dayatilake, G A; Diak, Robert; Breen, Ken C; Tustin, D Stuart; Costes, Evelyne; Chagné, David; Schaffer, Robert James; David, Karine Myriam

2012-01-13

Auxin is an important phytohormone for fleshy fruit development, having been shown to be involved in the initial signal for fertilisation, fruit size through the control of cell division and cell expansion, and ripening related events. There is considerable knowledge of auxin-related genes, mostly from work in model species. With the apple genome now available, it is possible to carry out genomics studies on auxin-related genes to identify genes that may play roles in specific stages of apple fruit development. High amounts of auxin in the seed compared with the fruit cortex were observed in 'Royal Gala' apples, with amounts increasing through fruit development. Injection of exogenous auxin into developing apples at the start of cell expansion caused an increase in cell size. An expression analysis screen of auxin-related genes involved in auxin reception, homeostasis, and transcriptional regulation showed complex patterns of expression in each class of gene. Two mapping populations were phenotyped for fruit size over multiple seasons, and multiple quantitative trait loci (QTLs) were observed. One QTL mapped to a region containing an Auxin Response Factor (ARF106). This gene is expressed during cell division and cell expansion stages, consistent with a potential role in the control of fruit size. The application of exogenous auxin to apples increased cell expansion, suggesting that endogenous auxin concentrations are at least one of the limiting factors controlling fruit size. The expression analysis of ARF106 linked to a strong QTL for fruit weight suggests that the auxin signal regulating fruit size could partially be modulated through the function of this gene. One class of gene (GH3) removes free auxin by conjugation to amino acids. The lower expression of these GH3 genes during rapid fruit expansion is consistent with the apple maximising auxin concentrations at this point.

A genomics approach to understanding the role of auxin in apple (Malus x domestica) fruit size control

PubMed Central

2012-01-01

Background Auxin is an important phytohormone for fleshy fruit development, having been shown to be involved in the initial signal for fertilisation, fruit size through the control of cell division and cell expansion, and ripening related events. There is considerable knowledge of auxin-related genes, mostly from work in model species. With the apple genome now available, it is possible to carry out genomics studies on auxin-related genes to identify genes that may play roles in specific stages of apple fruit development. Results High amounts of auxin in the seed compared with the fruit cortex were observed in 'Royal Gala' apples, with amounts increasing through fruit development. Injection of exogenous auxin into developing apples at the start of cell expansion caused an increase in cell size. An expression analysis screen of auxin-related genes involved in auxin reception, homeostasis, and transcriptional regulation showed complex patterns of expression in each class of gene. Two mapping populations were phenotyped for fruit size over multiple seasons, and multiple quantitative trait loci (QTLs) were observed. One QTL mapped to a region containing an Auxin Response Factor (ARF106). This gene is expressed during cell division and cell expansion stages, consistent with a potential role in the control of fruit size. Conclusions The application of exogenous auxin to apples increased cell expansion, suggesting that endogenous auxin concentrations are at least one of the limiting factors controlling fruit size. The expression analysis of ARF106 linked to a strong QTL for fruit weight suggests that the auxin signal regulating fruit size could partially be modulated through the function of this gene. One class of gene (GH3) removes free auxin by conjugation to amino acids. The lower expression of these GH3 genes during rapid fruit expansion is consistent with the apple maximising auxin concentrations at this point. PMID:22243694

Hydrodynamic gene delivery in human skin using a hollow microneedle device.

PubMed

Dul, M; Stefanidou, M; Porta, P; Serve, J; O'Mahony, C; Malissen, B; Henri, S; Levin, Y; Kochba, E; Wong, F S; Dayan, C; Coulman, S A; Birchall, J C

2017-11-10

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive human immunity drives remyelination in a mouse model of demyelination

PubMed Central

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand

2017-01-01

Abstract One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. PMID:28334918

Adaptive human immunity drives remyelination in a mouse model of demyelination.

PubMed

El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Zujovic, Violetta

2017-04-01

One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Restoring the encoding properties of a stochastic neuron model by an exogenous noise

PubMed Central

Paffi, Alessandra; Camera, Francesca; Apollonio, Francesca; d'Inzeo, Guglielmo; Liberti, Micaela

2015-01-01

Here we evaluate the possibility of improving the encoding properties of an impaired neuronal system by superimposing an exogenous noise to an external electric stimulation signal. The approach is based on the use of mathematical neuron models consisting of stochastic HH-like circuit, where the impairment of the endogenous presynaptic inputs is described as a subthreshold injected current and the exogenous stimulation signal is a sinusoidal voltage perturbation across the membrane. Our results indicate that a correlated Gaussian noise, added to the sinusoidal signal can significantly increase the encoding properties of the impaired system, through the Stochastic Resonance (SR) phenomenon. These results suggest that an exogenous noise, suitably tailored, could improve the efficacy of those stimulation techniques used in neuronal systems, where the presynaptic sensory neurons are impaired and have to be artificially bypassed. PMID:25999845

Sodic alkaline stress mitigation by exogenous melatonin in tomato needs nitric oxide as a downstream signal.

PubMed

Liu, Na; Gong, Biao; Jin, Zhiyong; Wang, Xiufeng; Wei, Min; Yang, Fengjuan; Li, Yan; Shi, Qinghua

2015-08-15

The present study was designed to determine the interactive effect of exogenous melatonin and nitric oxide (NO) on sodic alkaline stress mitigation in tomato seedlings. It was observed that exogenous melatonin treatment elevated NO levels in alkaline-stressed tomato roots. However, exogenous NO had little effects on melatonin levels. Importantly, melatonin-induced NO generation was accompanied by increased tolerance to alkaline stress. Chemical scavenging of NO reduced melatonin-induced alkaline stress tolerance and defense genes' expression. However, inhibition of melatonin biosynthesis had a little effect on NO-induced alkaline stress tolerance. These results strongly suggest that NO, acting as a downstream signal, is involved in the melatonin-induced tomato tolerance to alkaline stress. This process creates a new signaling pathway for improving stress tolerance in plant. Copyright © 2015 Elsevier GmbH. All rights reserved.

[Farmer's lung--a form of exogenous allergic alveolitis].

PubMed

Sambale, M; Liebetrau, G

1990-11-15

Exogenic allergic alveolitides are caused by organic dusts which contain bacteria, moulds or vegetable and animal antigens. The farmer's lung as a form of the exogenic allergic alveolitis is a rare disease. The uncharacteristic symptomatology in the initial phase and in particular the retarded beginning of the symptom after several hours handicap the timely recognition in an early phase of the disease so that curative therapeutic measures are rarely possible. The cases of the disease are found only at the chronic stage, at the stage of the pulmonary fibrosis. Then the prognosis is unfavourable. In the Central Clinic for Heart and Lung Diseases Bad Berka 1,110 patients with alveolitides and lung fibroses were diagnosed in the period from 1975 to 1988. 306 of them could be clarified as exogenic allergic alveolitis, 61 of them (19.8%) were farmer's lungs.

Endogenous versus Exogenous Origins of Crises

NASA Astrophysics Data System (ADS)

Sornette, Didier

Are large biological extinctions such as the Cretaceous/Tertiary KT boundary due to a meteorite, extreme volcanic activity or self-organized critical extinction cascades? Are commercial successes due to a progressive reputation cascade or the result of a well orchestrated advertisement? Determining the chain of causality for Xevents in complex systems requires disentangling interwoven exogenous and endogenous contributions with either no clear signature or too many signatures. Here, I review several efforts carried out with collaborators which suggest a general strategy for understanding the organizations of several complex systems under the dual effect of endogenous and exogenous fluctuations. The studied examples are: internet download shocks, book sale shocks, social shocks, financial volatility shocks, and financial crashes. Simple models are offered to quantitatively relate the endogenous organization to the exogenous response of the system. Suggestions for applications of these ideas to many other systems are offered.

Exogenous (automatic) attention to emotional stimuli: a review.

PubMed

Carretié, Luis

2014-12-01

Current knowledge on the architecture of exogenous attention (also called automatic, bottom-up, or stimulus-driven attention, among other terms) has been mainly obtained from studies employing neutral, anodyne stimuli. Since, from an evolutionary perspective, exogenous attention can be understood as an adaptive tool for rapidly detecting salient events, reorienting processing resources to them, and enhancing processing mechanisms, emotional events (which are, by definition, salient for the individual) would seem crucial to a comprehensive understanding of this process. This review, focusing on the visual modality, describes 55 experiments in which both emotional and neutral irrelevant distractors are presented at the same time as ongoing task targets. Qualitative and, when possible, meta-analytic descriptions of results are provided. The most conspicuous result is that, as confirmed by behavioral and/or neural indices, emotional distractors capture exogenous attention to a significantly greater extent than do neutral distractors. The modulatory effects of the nature of distractors capturing attention, of the ongoing task characteristics, and of individual differences, previously proposed as mediating factors, are also described. Additionally, studies reviewed here provide temporal and spatial information-partially absent in traditional cognitive models-on the neural basis of preattention/evaluation, reorienting, and sensory amplification, the main subprocesses involved in exogenous attention. A model integrating these different levels of information is proposed. The present review, which reveals that there are several key issues for which experimental data are surprisingly scarce, confirms the relevance of including emotional distractors in studies on exogenous attention.

The mechanisms of protection of antioxidants on Nostoc sphaeroides against UV-B radiation

NASA Astrophysics Data System (ADS)

Wang, G. H.

UV radiation is one of space harmful factor for earth organisms in space exploration In the present work we studied on the role of antioxidant system in Nostoc sphaeroides K u tz Cyanobacteria and the effects of exogenous antioxidant molecules on its photosynthetic rate under UV-B radiation It was found that UV-B radiation decreased the photosynthetic activity of cyanobacterium but promoted the activity of antioxidant system to protect photosystem II PSII and exogenous antioxidant sodium nitroprusside SNP N-acetylcysteine NAC had an obvious protection on PSII activity under UV-B radiation The activity of SOD Superoxide Dismutase EC 1 15 1 1 CAT Catalase EC 1 11 1 6 POD Peroxidase EC 1 11 1 7 and content of MDA and ASC were improved by 0 5mM and 1mM SNP but 0 1mM SNP decreased the activity of antioxide system Exogenous NAC addition decreased the activity of SOD POD CAT and the content MDA and ASC but exogenous NAC addition increased the content of GSH The results suggested that exogenous SNP and NAC may protect algae by different mechanisms in which SNP maybe play double roles as sources of reactive free radicals or ROS scavengers in formation of algae s protection of PSII under UV-B radiation while NAC does function as antioxidant reagent or precursor of glutathione which could protect PSII directly from UV-B radiation Keyword antioxidant system exogenous or endogenous antioxidant Nostoc sphaeroides photosynthesis UV-B radiation

The response of antioxidant systems in Nostoc sphaeroides against UV-B radiation and the protective effects of exogenous antioxidants

NASA Astrophysics Data System (ADS)

Wang, Gaohong; Hu, Chunxiang; Li, Dunhai; Zhang, Delu; Li, Xiaoyan; Chen, Kun; Liu, Yongding

UV radiation is one of many harmful factors found in space that are detrimental to organisms on earth in space exploration. In the present work, we examined the role of antioxidant system in Nostoc sphaeroides Kütz (Cyanobacterium) and the effects of exogenously applied antioxidant molecules on its photosynthetic rate under UV-B radiation. It was found that UV-B radiation promoted the activity of antioxidant system to protect photosystem II (PSII) and exogenously applied antioxidant: sodium nitroprusside (SNP) and N-acetylcysteine (NAC) had an obvious protection on PSII activity under UV-B radiation. The activity of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7) and content of MDA (malondialdehyde) and ASC (ascorbate) were improved by 0.5 mM and 1 mM SNP, but 0.1 mM SNP decreased the activity of antioxidant system. Addition of exogenous NAC decreased the activity of SOD, POD, CAT and the content MDA and ASC. In contrast, exogenously applied NAC increased GSH content. The results suggest that exogenous SNP and NAC may protect algae by different mechanisms: SNP may play double roles as both sources of reactive free radicals as well as ROS scavengers in mediating the protective role of PSII on algae under UV-B radiation. On the other hand, NAC functions as an antioxidant or precursor of glutathione, which could protect PSII directly from UV-B radiation.

Neural mechanisms mediating contingent capture of attention by affective stimuli

PubMed Central

Reeck, Crystal; LaBar, Kevin S.; Egner, Tobias

2013-01-01

Attention is attracted exogenously by physically salient stimuli, but this effect can be dampened by endogenous attention settings, a phenomenon called “contingent capture”. Emotionally salient stimuli are also thought to exert a strong exogenous influence on attention, especially in anxious individuals, but whether and how top-down attention can ameliorate bottom-up capture by affective stimuli is currently unknown. Here, we paired a novel spatial cueing task with functional magnetic resonance imaging (fMRI) in order to investigate contingent capture as a function of the affective salience of bottom-up cues (face stimuli) and individual differences in trait anxiety. In the absence of top-down cues, exogenous stimuli validly cueing targets facilitated attention in low anxious participants, regardless of affective salience. However, while high anxious participants exhibited similar facilitation following neutral exogenous cues, this facilitation was completely absent following affectively negative exogenous cues. Critically, these effects were contingent on endogenous attentional settings, such that explicit top-down cues presented prior to the appearance of exogenous stimuli removed anxious individuals’ sensitivity to affectively salient stimuli. FMRI analyses revealed a network of brain regions underlying this variability in affective contingent capture across individuals, including the fusiform face area (FFA), posterior ventrolateral frontal cortex, and supplementary motor area. Importantly, activation in the posterior ventrolateral frontal cortex and the supplementary motor area fully mediated the effects observed in FFA, demonstrating a critical role for these frontal regions in mediating attentional orienting and interference resolution processes when engaged by affectively salient stimuli. PMID:22360642

Dihydroxyacetone induces G2/M arrest and apoptotic cell death in A375P melanoma cells.

PubMed

Smith, Kelly R; Granberry, Molley; Tan, Marcus C B; Daniel, Casey L; Gassman, Natalie R

2018-03-01

The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by-product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress. Therefore, exogenous and endogenous exposures to DHA may be harmful to cells, and it has already been demonstrated that exogenous exposure to DHA is cytotoxic in immortalized keratinocytes. Still, little is known about the exogenous DHA exposure effects on other skin components. In this study, we explore the effects of exogenous DHA exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to DHA and displayed a transient burst of reactive oxygen species within an hour of exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and apoptosis, monitored by the cleavage of PARP-1 and Caspase-3, was detected within 72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to DHA has cytotoxic effects in our selected cell model and indicates the need to further investigate the exogenous exposure effects of DHA in other relevant exposure models. © 2017 Wiley Periodicals, Inc.

Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy.

PubMed

Zhu, Ying; Zhao, Ke-Ke; Tong, Yao; Zhou, Ya-Li; Wang, Yi-Xiao; Zhao, Pei-Quan; Wang, Zhao-Yang

2016-05-31

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD(+)) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD(+) administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD(+) administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD(+) administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD(+) against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD(+) administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD(+) administration might be potential value for the treatment of AMD.

Genome-wide identification and characterization of the NF-Y gene family in grape (vitis vinifera L.).

PubMed

Ren, Chong; Zhang, Zhan; Wang, Yi; Li, Shaohua; Liang, Zhenchang

2016-08-11

Nuclear factor Y (NF-Y) transcription factor is composed of three distinct subunits: NF-YA, NF-YB and NF-YC. Many members of NF-Y family have been reported to be key regulators in plant development, phytohormone signaling and drought tolerance. However, the function of the NF-Y family is less known in grape (Vitis vinifera L.). A total of 34 grape NF-Y genes that distributed unevenly on grape (V. vinifera) chromosomes were identified in this study. Phylogenetic analysis was performed to predict functional similarities between Arabidopsis thaliana and grape NF-Y genes. Comparison of the structures of grape NF-Y genes (VvNF-Ys) revealed their functional conservation and alteration. Furthermore, we investigated the expression profiles of VvNF-Ys in response to various stresses, phytohormone treatments, and in leaves and grape berries with various sugar contents at different developmental stages. The relationship between VvNF-Y transcript levels and sugar content was examined to select candidates for exogenous sugar treatments. Quantitative real-time PCR (qPCR) indicated that many VvNF-Ys responded to different sugar stimuli with variations in transcript abundance. qPCR and publicly available microarray data suggest that VvNF-Ys exhibit distinct expression patterns in different grape organs and developmental stages, and a number of VvNF-Ys may participate in responses to multiple abiotic and biotic stresses, phytohormone treatments and sugar accumulation or metabolism. In this study, we characterized 34 VvNF-Ys based on their distributions on chromosomes, gene structures, phylogenetic relationship with Arabidopsis NF-Y genes, and their expression patterns. The potential roles of VvNF-Ys in sugar accumulation or metabolism were also investigated. Altogether, the data provide significant insights on VvNF-Ys, and lay foundations for further functional studies of NF-Y genes in grape.

Disturbances in Pro-Oxidant-Antioxidant Balance after Passive Body Overheating and after Exercise in Elevated Ambient Temperatures in Athletes and Untrained Men

PubMed Central

Pilch, Wanda; Szygula, Zbigniew; Tyka, Anna K.; Palka, Tomasz; Tyka, Aleksander; Cison, Tomasz; Pilch, Pawel; Teleglow, Aneta

2014-01-01

The aim of the study was to investigate pro-oxidant-antioxidant balance in two series of examinations with two types of stressors (exogenous heat and the combined exogenous and endogenous heat) in trained and untrained men. The exogenous stressor was provided by Finnish sauna session, whereas the combined stressor was represented by the exercise in elevated ambient temperature. The men from the two groups performed the physical exercise on a cycle ergometer with the load of 53±2% maximal oxygen uptake at the temperature of 33±1°C and relative humidity of 70% until their rectal temperature rose by 1.2°C. After a month from completion of the exercise test the subjects participated in a sauna bathing session with the temperature of 96±2°C, and relative humidity of 16±5%. 15-minutes heating and 2-minute cool-down in a shower with the temperature of 20°C was repeated until rectal temperature rose by 1.2°C compared to the initial value. During both series of tests rectal temperature was measured at 5-minute intervals. Before both series of tests and after them body mass was measured and blood samples were taken for biochemical tests. Serum total protein, serum concentration of lipid peroxidation products and serum antioxidants were determined. The athletes were characterized by higher level of antioxidant status and lower concentration of lipid peroxidation products. Physical exercise at elevated ambient temperature caused lower changes in oxidative stress indices compared to sauna bathing. Sauna induced a shift in pro-oxidant-antioxidant balance towards oxidation, which was observed less intensively in the athletes compared to the untrained men. This leads to the conclusion that physical exercise increases tolerance to elevated ambient temperature and oxidative stress. PMID:24465535

Wheat bHLH-type transcription factor gene TabHLH1 is crucial in mediating osmotic stresses tolerance through modulating largely the ABA-associated pathway.

PubMed

Yang, Tongren; Yao, Sufei; Hao, Lin; Zhao, Yuanyuan; Lu, Wenjing; Xiao, Kai

2016-11-01

Wheat bHLH family gene TabHLH1 is responsive to drought and salt stresses, and it acts as one crucial regulator in mediating tolerance to aforementioned stresses largely through an ABA-associated pathway. Osmotic stresses are adverse factors for plant growth and crop productivity. In this study, we characterized TabHLH1, a gene encoding wheat bHLH-type transcription factor (TF) protein, in mediating plant adaptation to osmotic stresses. TabHLH1 protein contains a conserved basic-helix-loop-helix (bHLH) domain shared by its plant counterparts. Upon PEG-simulated drought stress, salt stress, and exogenous abscisic acid (ABA), the TabHLH1 transcripts in roots and leaves were induced. Under PEG-simulated drought stress and salt stress treatments, the tobacco seedlings with TabHLH1 overexpression exhibited improved growth and osmotic stress-associated traits, showing increased biomass and reduced leaf water loss rate (WLR) relative to wild type (WT). The transgenic lines also possessed promoted stomata closure under drought stress, salt stress, and exogenous ABA and increased proline and soluble sugar contents and reduced hydrogen peroxide (H 2 O 2 ) amount under osmotic stress conditions, indicating that TabHLH1-mediated osmolyte accumulation and cellular ROS homeostasis contributed to the drought stress and salt stress tolerance. NtPYL12 and NtSAPK2;1, the genes encoding ABA receptor and SnRK2 family kinase, respectively, showed up-regulated expression in lines overexpressing TabHLH1 under osmotic stress and exogenous ABA conditions; overexpression of them conferred plants modified stomata movement, leaf WLR, and growth feature under drought and high salinity, suggesting that these ABA-signaling genes are mediated by wheat TabHLH1 gene and involved in regulating plant responses to simulated drought and salt stresses. Our investigation indicates that the TabHLH1 gene plays critical roles in plant tolerance to osmotic stresses largely through an ABA-dependent pathway.

Regulation of human retinal blood flow by endothelin-1.

PubMed

Polak, Kaija; Luksch, Alexandra; Frank, Barbara; Jandrasits, Kerstin; Polska, Elzbieta; Schmetterer, Leopold

2003-05-01

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.

Hevin Plays a Pivotal Role in Corneal Wound Healing

PubMed Central

Chaurasia, Shyam S.; Perera, Promoda R.; Poh, Rebekah; Lim, Rayne R.; Wong, Tina T.; Mehta, Jodhbir S.

2013-01-01

Background Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin-/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. Methodology/Principal Findings Wild type (WT) and hevin -/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin -/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. Conclusions/Significance Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin -/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing. PMID:24303054

Physiological and molecular genetic evaluation of the dechlorination agent, pyridine-2,6-bis(monothiocarboxylic acid) (PDTC) as a secondary siderophore of Pseudomonas.

PubMed

Lewis, Thomas A; Leach, Lynne; Morales, Sergio; Austin, Paula R; Hartwell, Hadley J; Kaplan, Benjamin; Forker, Cynthia; Meyer, Jean-Marie

2004-02-01

The bacterial metabolite and transition metal chelator pyridine-2,6-dithiocarboxylic acid (PDTC), promotes a novel and effective means of dechlorination of the toxic and carcinogenic pollutant, carbon tetrachloride. Pyridine-2,6-dithiocarboxylic acid has been presumed to act as a siderophore in the Pseudomonas strains known to produce it. To explore further the physiological function of PDTC production, we have examined its regulation, the phenotype of PDTC-negative (pdt) mutants, and envelope proteins associated with PDTC in P. putida strain DSM 3601. Aspects of the regulation of PDTC production and outer membrane protein composition were consistent with siderophore function. Pyridine-2,6-dithiocarboxylic acid production was coordinated with production of the well-characterized siderophore pyoverdine; exogenously added pyoverdine led to decreased PDTC production, and added PDTC led to decreased pyoverdine production. Positive regulation of a chromosomal pdtI-xylE transcriptional fusion, and of a 66 kDa outer membrane protein (IROMP), was seen in response to exogenous PDTC. Tests with transition metal chelators indicated that PDTC could provide a benefit under conditions of metal limitation; the loss of PDTC biosynthetic capacity caused by a pdtI transposon insertion resulted in increased sensitivity to 1,10-phenanthroline, a chelator that has high affinity for a range of divalent transition metals (e.g. Fe(2+), Cu(2+), Zn(2+)). Exogenously added PDTC could also suppress a phenotype of pyoverdine-negative (Pvd-) mutants, that of sensitivity to EDDHA, a chelator with higher affinity and specificity for Fe(3+). Measurement of 59Fe incorporation showed uptake from 59Fe:PDTC by DSM 3601 grown in low-iron medium, but not by cells grown in high iron medium, or by the pdtI mutant, which did not show expression of the 66 kDa envelope protein. These data verified a siderophore function for PDTC, and have implicated it in the uptake of transition metals in addition to iron.

Transcriptome Analysis of the Effects of Shell Removal and Exogenous Gibberellin on Germination of Zanthoxylum Seeds.

PubMed

Sun, Jikang; Wang, Ping; Zhou, Tao; Rong, Jian; Jia, Hao; Liu, Zhiming

2017-08-17

The zanthoxylum seeds are oil-rich and have a very thick, dense and oily shell. In the natural conditions the seeds have a very low germination rate. Prior to treatment with GAs to promote germination, the seeds were usually soaked in sulfuric acid to remove shells easily. A high-throughput sequencing of mRNAs was performed to investigate the effects of the above treatments on the germination of zanthoxylum seeds. Seven libraries were assembled into 100,982 unigenes and 59,509 unigenes were annotated. We focused on the expression profiles of the key genes related to the oil metabolisms and hormone regulations during seed germination. Our data indicated the endogenous ABA of seeds was rich. The effects that the exogenous GAs promoted germination were apparent in the secong day of germination. Especially, for the first time our results indicated the exogenous GAs lowered the aerobic metabolism including the oil metabolisms during imbibition. We inferred that the exogenous GAs had inhibitory effects on the oil metabolisms to avoide oxidative damages to the imbibed seeds, and the seed shell played the role similiar to the exogenous GAs in the initial stage of germination in the natural conditions.

Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit, pigeon and rat liver: implications for lipogenesis.

PubMed

Wiese, T J; Wuensch, S A; Ray, P D

1996-08-01

Rabbit, pigeon and rat liver mitochondria convert exogenous phosphoenolpyruvate and acetylcarnitine to citrate at rates of 14, 74 and 8 nmol/15 min/mg protein. Citrate formation is dependent on exogenous HCO3-, is increased consistently by exogenous nucleotides (GDP, IDP, GTP, ADP, ATP) and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate is not made from pyruvate alone or combined with acetylcarnitine. Pigeon and rat liver mitochondria make large amounts of citrate from exogenous succinate, suggesting the presence of an endogenous source of acetyl units or means of converting oxalacetate to acetyl units. Citrate synthesis from succinate by pigeon and rabbit mitochondria is increased significantly by exogenous acetylcarnitine. Pigeon and rat liver contain 80 and 15 times, respectively, more ATP:citrate lyase activity than does rabbit liver. Data suggest that mitochondrial phosphoenolpyruvate carboxykinase in vivo could convert glycolysis-derived phosphoenolpyruvate to oxalacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a carbon source via ATP:citrate lyase and NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.

Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria*

PubMed Central

Yao, Jiangwei; Bruhn, David F.; Frank, Matthew W.; Lee, Richard E.; Rock, Charles O.

2016-01-01

Neisseria is a Gram-negative pathogen with phospholipids composed of straight chain saturated and monounsaturated fatty acids, the ability to incorporate exogenous fatty acids, and lipopolysaccharides that are not essential. The FabI inhibitor, AFN-1252, was deployed as a chemical biology tool to determine whether Neisseria can bypass the inhibition of fatty acid synthesis by incorporating exogenous fatty acids. Neisseria encodes a functional FabI that was potently inhibited by AFN-1252. AFN-1252 caused a dose-dependent inhibition of fatty acid synthesis in growing Neisseria, a delayed inhibition of growth phenotype, and minimal inhibition of DNA, RNA, and protein synthesis, showing that its mode of action is through inhibiting fatty acid synthesis. Isotopic fatty acid labeling experiments showed that Neisseria encodes the ability to incorporate exogenous fatty acids into its phospholipids by an acyl-acyl carrier protein-dependent pathway. However, AFN-1252 remained an effective antibacterial when Neisseria were supplemented with exogenous fatty acids. These results demonstrate that extracellular fatty acids are activated by an acyl-acyl carrier protein synthetase (AasN) and validate type II fatty acid synthesis (FabI) as a therapeutic target against Neisseria. PMID:26567338

Hematopoietic Responses to Lipopolysaccharide in C57BL/10Sn and C57BL/10ScN Strain Mice

DTIC Science & Technology

1982-12-01

Responses of endogenous (E-CFU) stem cells as well as bone marrow and spleen-derived exogenous (CFU-s) stem cells, granulocyte-macrophage (GM;-CFC... endogenous (E-CFU) stem cells as well as bone marrow and spleen-derived exogenous (CFU-s) stem cells, granulocyte-macrophage (GM-CFC) and macrophage (M...IOScN in comparison to the normal C57BL/1OSn strain mice, as measured by endogenous (E-CFU) and exogenous (CFU-s) stem cells and committed granulocyte

Exogenous heat shock protein HSP70 reduces response of human neuroblastoma cells to lipopolysaccharide.

PubMed

Yurinskaya, M M; Funikov, S Y; Evgen'ev, M B; Vinokurov, M G

2016-07-01

The effect of exogenous heat shock protein HSP70 and lipopolysaccharide (LPS) on the production of reactive oxygen species (ROS), TNFα secretion, and mRNA expression by human neuroblastoma SK-N-SH cells. It was shown that exogenous HSP70 protects neuroblastoma cells from the action of LPS. The protection mechanism of HSP70 includes a reduction in the production of ROS and TNFα and a decrease in the expression of TLR4 and IL-1β mRNA in SK-N-SH cells induced by LPS.

The effects of exogenous hormones on rooting process and the activities of key enzymes of Malus hupehensis stem cuttings.

PubMed

Zhang, Wangxiang; Fan, Junjun; Tan, Qianqian; Zhao, Mingming; Zhou, Ting; Cao, Fuliang

2017-01-01

Malus hupehensis is an excellent Malus rootstock species, known for its strong adverse-resistance and apomixes. In the present study, stem cuttings of M. hupehensis were treated with three types of exogenous hormones, including indole acetic acid (IAA), naphthalene acetic acid (NAA), or green growth regulator (GGR). The effects and mechanisms of exogenous hormone treatment and antioxidant enzyme activity on adventitious root formation were investigated. The results showed that the apparent morphology of the adventitious root had four stages, including root pre-emergence stage (S0), early stage of root formation (S1), massive root formation stage (S2), and later stage of root formation (S3). The suitable concentrations of the three exogenous hormones, IAA, NAA and GGR, were 100 mg·L-1, 300 mg·L-1, and 300 mg·L-1, respectively. They shortened the rooting time by 25-47.4% and increased the rooting percentages of cuttings by 0.9-1.3 times, compared with that in the control. The dispersion in S0 stage was 3.6 times of that in the S1 stage after exogenous hormone application. The earlier the third critical point (P3) appeared, the shorter the rooting time and the greater the rooting percentage of the cuttings. During rhizogenesis, the activities of three antioxidant enzymes (POD, SOD, and PPO) showed an A-shaped trend. However, peak values of enzyme activity appeared at different points, which were 9 d before the P3, P3, and the fourth critical point (P4), respectively. Exogenous hormone treatment reduced the time to reach the peak value by 18 days, although the peak values of the enzymatic activities did not significantly changed. Our results suggested that exogenous hormone treatment mainly acted during the root pre-emergence stage, accelerated the synthesis of antioxidant enzymes, reduced the rooting time, and consequently promoted root formation. The three kinds of antioxidant enzymes acted on different stages of rooting.

Sequence comparison in the crossover region of an oncogenic avian retrovirus recombinant and its nononcogenic parent: Genetic regions that control growth rate and oncogenic potential

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

Tsichlis, P.N.; Donehower, L.; Hager, G.

1982-11-01

NTRE is an avian retrovirus recombinant of the endogeneous nononcogenic Rous-associated virus-0 (RAV-0) and the oncogenic, exogeneous, transformation-defective (td) Prague strain of Rous sarcoma virus B (td-PrRSV-B). Oligonucleotide mapping had shown that the recombinant virus is indistinguishable from its RAV-0 parent except for the 3'-end sequences, which were derived from td-PrRSV-B. However, the virus exhibits properties which are typical of an exogenous virus: it grows to high titers in tissue culture, and it is oncogenic in vivo. To accurately define the genetic region responsible for these properties, the authors determined the nucleotide sequences of the recombinant and its RAV-0 parentmore » by using molecular clones of their DNA. These were compared with sequences already available for PrRSV-C, a virus closely related to the exogenous parent td-PrRSV-B. The results suggested that the crossover event which generated NTRE 7 took place in a region -501 to -401 nucleotides from the 3' end of the td-PrRSV parental genome and that sequences to the right of the recombination region were responsible for its growth properties and oncogenic potential. Since the exogenous-virus-specific sequences are expected to be missing from transformation-defective mutants of the Schmidt-Ruppin strain of RSV, which, like other exogeneous viruses, grow to high tiers in tissue culture and are oncogenic in vivo, the authors concluded that the growth properties and oncogenic potential of the exogeneous viruses are determined by sequences in the U3 region of the long terminal repeat. However, the authors propose that the exogeneous-virus-specific region may play a role in determining the oncogenic spectrum of a given oncogenic virus.« less

Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats.

PubMed

Lai, Sarah W; de Heuvel, Elaine; Wallace, Laurie E; Hartmann, Bolette; Holst, Jens J; Brindle, Mary E; Chelikani, Prasanth K; Sigalet, David L

2017-01-01

To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study.

Exogenous Calcium Enhances the Photosystem II Photochemistry Response in Salt Stressed Tall Fescue.

PubMed

Wang, Guangyang; Bi, Aoyue; Amombo, Erick; Li, Huiying; Zhang, Liang; Cheng, Cheng; Hu, Tao; Fu, Jinmin

2017-01-01

Calcium enhances turfgrass response to salt stress. However, little is known about PSII photochemical changes when exogenous calcium was applied in salinity-stressed turfgrass. Here, we probe into the rearrangements of PSII electron transport and endogenous ion accumulation in tall fescue ( Festuca arundinacea Schreber) treated with exogenous calcium under salt stress. Three-month-old seedlings of genotype "TF133" were subjected to the control (CK), salinity (S), salinity + calcium nitrate (SC), and salinity + ethylene glycol tetraacetic acid (SE). Calcium nitrate and ethylene glycol tetraacetic acid was used as exogenous calcium donor and calcium chelating agent respectively. At the end of a 5-day duration treatment, samples in SC regime had better photochemistry performance on several parameters than salinity only. Such as the Area (equal to the plastoquinone pool size), N (number of [Formula: see text] redox turnovers until F m is reached), ψE 0 , or δRo (Efficiencdy/probability with which a PSII trapped electron is transferred from Q A to Q B or PSI acceptors), ABS/RC (Absorbed photon flux per RC). All the above suggested that calcium enhanced the electron transfer of PSII (especially beyond [Formula: see text]) and prevented reaction centers from inactivation in salt-stressed tall fescue. Furthermore, both grass shoot and root tissues generally accumulated more C, N, Ca 2+ , and K + in the SC regime than S regime. Interrelated analysis indicated that ψE 0 , δRo, ABS/RC, C, and N content in shoots was highly correlated to each other and significantly positively related to Ca 2+ and K + content in roots. Besides, high salt increased ATP6E and CAMK2 transcription level in shoot at 1 and 5 day, respectively while exogenous calcium relieved it. In root, CAMK2 level was reduced by Salinity at 5 day and exogenous calcium recovered it. These observations involved in electron transport capacity and ion accumulation assist in understanding better the protective role of exogenous calcium in tall fescue under salt stress.

Effects of exogenous glutathione and cysteine on growth, lead accumulation, and tolerance of Iris lactea var. chinensis.

PubMed

Yuan, Haiyan; Zhang, Yongxia; Huang, Suzhen; Yang, Yongheng; Gu, Chunsun

2015-02-01

Effects of exogenous reduced glutathione (GSH) and cysteine (Cys) on growth, lead (Pb) accumulation, and nonprotein thiol (NPT) contents of Iris lactea var. chinensis under 100 and 500 mg L(-1) Pb stress were studied. Our results showed that 500 mg L(-1) Pb stress caused a dramatical decline in fresh weights, while the reduction of aboveground biomass was alleviated by exogenous GSH and Cys even though keeping higher Pb contents in roots and shoots. Exogenous GSH and Cys could enhance Pb accumulation in the shoots and roots compared with single Pb treatment. The promoting effect of GSH to Pb accumulation was larger than the effect of Cys, and the Pb contents in the shoots and roots treated with 500 mg L(-1) Pb + GSH reached 1,712 and 14,603 mg kg(-1), about 4.19 and 2.78 times of single 500 mg L(-1) Pb treatment, respectively. Microscopic imaging of Pb in roots and leaves showed that higher intensive fluorescence was observed in cell wall of root epidermis, stele, vascular tissues of the roots, and sclerenchyma cells of leaves treated with 500 mg L(-1) Pb + GSH and treated with 500 mg L(-1) Pb + Cys. Exogenous GSH had an apparent promoting effect on root and shoot GSH synthesis, while exogenous Cys reduced the synthesis of cellular GSH in shoot and increased Cys contents. Pb only induced the synthesis of phytochelatin (PC)2 in roots, and the PC2 content declined in GSH- and Cys-treated plant roots. These results suggested that GSH synthesis was a more effective approach to improve Pb accumulation and translocation of I. lactea var. chinensis. Further analysis of protein expression in plants by exogenous GSH and buthionine sulfoximine (BSO) application showed that the proteins regulated by GSH and BSO may constitute various enzymes involved in GSH biosynthesis and play certain roles in Pb accumulation and tolerance of I. lactea var. chinensis.

Effects of exogenous glucagon-like peptide-2 and distal bowel resection on intestinal and systemic adaptive responses in rats

PubMed Central

de Heuvel, Elaine; Wallace, Laurie E.; Hartmann, Bolette; Holst, Jens J.; Brindle, Mary E.; Chelikani, Prasanth K.; Sigalet, David L.

2017-01-01

Objective To determine the effects of exogenous glucagon-like peptide-2 (GLP-2), with or without massive distal bowel resection, on adaptation of jejunal mucosa, enteric neurons, gut hormones and tissue reserves in rats. Background GLP-2 is a gut hormone known to be trophic for small bowel mucosa, and to mimic intestinal adaptation in short bowel syndrome (SBS). However, the effects of exogenous GLP-2 and SBS on enteric neurons are unclear. Methods Sprague Dawley rats were randomized to four treatments: Transected Bowel (TB) (n = 8), TB + GLP-2 (2.5 nmol/kg/h, n = 8), SBS (n = 5), or SBS + GLP-2 (2.5 nmol/kg/h, n = 9). SBS groups underwent a 60% jejunoileal resection with cecectomy and jejunocolic anastomosis. All rats were maintained on parenteral nutrition for 7 d. Parameters measured included gut morphometry, qPCR for hexose transporter (SGLT-1, GLUT-2, GLUT-5) and GLP-2 receptor mRNA, whole mount immunohistochemistry for neurons (HuC/D, VIP, nNOS), plasma glucose, gut hormones, and body composition. Results Resection increased the proportion of nNOS immunopositive myenteric neurons, intestinal muscularis propria thickness and crypt cell proliferation, which were not recapitulated by GLP-2 therapy. Exogenous GLP-2 increased jejunal mucosal surface area without affecting enteric VIP or nNOS neuronal immunopositivity, attenuated resection-induced reductions in jejunal hexose transporter abundance (SGLT-1, GLUT-2), increased plasma amylin and decreased peptide YY concentrations. Exogenous GLP-2 attenuated resection-induced increases in blood glucose and body fat loss. Conclusions Exogenous GLP-2 stimulates jejunal adaptation independent of enteric neuronal VIP or nNOS changes, and has divergent effects on plasma amylin and peptide YY concentrations. The novel ability of exogenous GLP-2 to modulate resection-induced changes in peripheral glucose and lipid reserves may be important in understanding the whole-body response following intestinal resection, and is worthy of further study. PMID:28738080

Exogenous Calcium Enhances the Photosystem II Photochemistry Response in Salt Stressed Tall Fescue

PubMed Central

Wang, Guangyang; Bi, Aoyue; Amombo, Erick; Li, Huiying; Zhang, Liang; Cheng, Cheng; Hu, Tao; Fu, Jinmin

2017-01-01

Calcium enhances turfgrass response to salt stress. However, little is known about PSII photochemical changes when exogenous calcium was applied in salinity-stressed turfgrass. Here, we probe into the rearrangements of PSII electron transport and endogenous ion accumulation in tall fescue (Festuca arundinacea Schreber) treated with exogenous calcium under salt stress. Three-month-old seedlings of genotype “TF133” were subjected to the control (CK), salinity (S), salinity + calcium nitrate (SC), and salinity + ethylene glycol tetraacetic acid (SE). Calcium nitrate and ethylene glycol tetraacetic acid was used as exogenous calcium donor and calcium chelating agent respectively. At the end of a 5-day duration treatment, samples in SC regime had better photochemistry performance on several parameters than salinity only. Such as the Area (equal to the plastoquinone pool size), N (number of QA- redox turnovers until Fm is reached), ψE0, or δRo (Efficiencdy/probability with which a PSII trapped electron is transferred from QA to QB or PSI acceptors), ABS/RC (Absorbed photon flux per RC). All the above suggested that calcium enhanced the electron transfer of PSII (especially beyond QA-) and prevented reaction centers from inactivation in salt-stressed tall fescue. Furthermore, both grass shoot and root tissues generally accumulated more C, N, Ca2+, and K+ in the SC regime than S regime. Interrelated analysis indicated that ψE0, δRo, ABS/RC, C, and N content in shoots was highly correlated to each other and significantly positively related to Ca2+ and K+ content in roots. Besides, high salt increased ATP6E and CAMK2 transcription level in shoot at 1 and 5 day, respectively while exogenous calcium relieved it. In root, CAMK2 level was reduced by Salinity at 5 day and exogenous calcium recovered it. These observations involved in electron transport capacity and ion accumulation assist in understanding better the protective role of exogenous calcium in tall fescue under salt stress. PMID:29250091

Cretaceous-Tertiary findings, paradigms and problems

NASA Technical Reports Server (NTRS)

Officer, C. B.; Drake, C. L.

1988-01-01

The asteroid hypothesis has stimulated numerous studies of the paleontological record at Cretaceous/Tertiary time as well as of geological indicators of environmental crisis preserved in the rock record. Both extinctions and geological anomalies often occur at times that do not appear to be synchronous or instantaneous. The record includes paleontological indicators of dinosaurs, terrestrial flora, marine planktonic organisms, and shallow water marine macrofauna and geological phenomena include occurrences of iridium and other platinum metals, trace elements, clay mineralogy, shocked minerals, soot, microspherules, and isotopes of osmium, strontium and carbon. These findings are reviewed in the context of the alternate hypotheses of an exogenic cause, involving either a single asteroid impact or multiple commentary impacts, and an endogenic cause, involving intense global volcanism and major sea level regression.

Nanodiamonds do not provide unique evidence for a Younger Dryas impact

PubMed Central

Tian, H.; Schryvers, D.; Claeys, Ph.

2011-01-01

Microstructural, δ13C isotope and C/N ratio investigations were conducted on excavated material from the black Younger Dryas boundary in Lommel, Belgium, aiming for a characterisation of the carbon content and structures. Cubic diamond nanoparticles are found in large numbers. The larger ones with diameters around or above 10 nm often exhibit single or multiple twins. The smaller ones around 5 nm in diameter are mostly defect-free. Also larger flake-like particles, around 100 nm in lateral dimension, with a cubic diamond structure are observed as well as large carbon onion structures. The combination of these characteristics does not yield unique evidence for an exogenic impact related to the investigated layer. PMID:21173270

Endocrine effects of prenatal exposure to PCBs, dioxins, and other xenobiotics: implications for policy and future research.

PubMed Central

Birnbaum, L S

1994-01-01

Recent reports have suggested that environmental chemicals may be associated with endocrine alterations in people, wildlife, and experimental animals. Pharmacological investigations as well as natural poisoning episodes have led to the association between exogenous chemicals and alterations in multiple hormonal systems. Persistent environmental contaminants such as dioxins and PCBs have been shown to modulate the activities of several different hormones. The unborn child or the neonate may be at special risk from these chemicals because of rapid growth and development, in addition to enhanced exposure. Because most exposure to these persistent chemicals is via food, changes in dietary habits and/or reduced contamination of the food supply may be required. PMID:7895708

BIODEGRADATION OF SIMPLE CHEMICAL MIXTURES IN SOILS

EPA Science Inventory

Exogenous cultures of microorganisms are often utilized to enhance bioremediation. The purpose of this study was to compare the capabilities of two exogenous microbial cultures, Pseudomonas aeruginosa and Phanerochaete sordida, and an indigenous population to detoxify soil amende...

One-shot exogenous interventions increase subsequent coordination in Denmark, Spain and Ghana

PubMed Central

Thorsen, Bo Jellesmark

2017-01-01

Everyday, we are bombarded with periodic, exogenous appeals and instructions on how to behave. How do these appeals and instructions affect subsequent coordination? Using experimental methods, we investigate how a one-time exogenous instruction affects subsequent coordination among individuals in a lab. Participants play a minimum effort game repeated 5 times under fixed matching with a one-time behavioral instruction in either the first or second round. Since coordination behavior may vary across countries, we run experiments in Denmark, Spain and Ghana, and map cross-country rankings in coordination with known national measures of fractualization, uncertainty avoidance and long-term orientation. Our results show that exogenous interventions increase subsequent coordination, with earlier interventions yielding better coordination than later interventions. We also find that cross-country rankings in coordination map with published national measures of fractualization, uncertainty avoidance, and long-term orientation. PMID:29145411

Using exogenous variables in testing for monotonic trends in hydrologic time series

USGS Publications Warehouse

Alley, William M.

1988-01-01

One approach that has been used in performing a nonparametric test for monotonic trend in a hydrologic time series consists of a two-stage analysis. First, a regression equation is estimated for the variable being tested as a function of an exogenous variable. A nonparametric trend test such as the Kendall test is then performed on the residuals from the equation. By analogy to stagewise regression and through Monte Carlo experiments, it is demonstrated that this approach will tend to underestimate the magnitude of the trend and to result in some loss in power as a result of ignoring the interaction between the exogenous variable and time. An alternative approach, referred to as the adjusted variable Kendall test, is demonstrated to generally have increased statistical power and to provide more reliable estimates of the trend slope. In addition, the utility of including an exogenous variable in a trend test is examined under selected conditions.

Exogenous calcium improves viability of biocontrol yeasts under heat stress by reducing ROS accumulation and oxidative damage of cellular protein.

PubMed

An, Bang; Li, Boqiang; Qin, Guozheng; Tian, Shiping

2012-08-01

In this article, we investigated the effect of exogenous calcium on improving viability of Debaryomyces hansenii and Pichia membranaefaciens under heat stress, and evaluated the role of calcium in reducing oxidant damage of proteins in the yeast cells. The results indicated that high concentration of exogenous calcium in culture medium was beneficial for enhancing the tolerance of the biocontrol yeasts to heat stress. The possible mechanism of calcium improving the viability of yeasts was attributed to enhancement of antioxidant enzyme activities, decrease in ROS accumulation and reduction of oxidative damage of intracellular protein in yeast cells under heat stress. D. hansenii is more sensitive to calcium as compared to P. membranaefaciens. Our results suggest that application of exogenous calcium combined with biocontrol yeasts is a practical approach for the control of postharvest disease in fruit.

One-shot exogenous interventions increase subsequent coordination in Denmark, Spain and Ghana.

PubMed

Abatayo, Anna Lou; Thorsen, Bo Jellesmark

2017-01-01

Everyday, we are bombarded with periodic, exogenous appeals and instructions on how to behave. How do these appeals and instructions affect subsequent coordination? Using experimental methods, we investigate how a one-time exogenous instruction affects subsequent coordination among individuals in a lab. Participants play a minimum effort game repeated 5 times under fixed matching with a one-time behavioral instruction in either the first or second round. Since coordination behavior may vary across countries, we run experiments in Denmark, Spain and Ghana, and map cross-country rankings in coordination with known national measures of fractualization, uncertainty avoidance and long-term orientation. Our results show that exogenous interventions increase subsequent coordination, with earlier interventions yielding better coordination than later interventions. We also find that cross-country rankings in coordination map with published national measures of fractualization, uncertainty avoidance, and long-term orientation.

Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids.

PubMed

Louie, Sharon M; Roberts, Lindsay S; Mulvihill, Melinda M; Luo, Kunxin; Nomura, Daniel K

2013-10-01

De novo lipogenesis is considered the primary source of fatty acids for lipid synthesis in cancer cells, even in the presence of exogenous fatty acids. Here, we have used an isotopic fatty acid labeling strategy coupled with metabolomic profiling platforms to comprehensively map palmitic acid incorporation into complex lipids in cancer cells. We show that cancer cells and tumors robustly incorporate and remodel exogenous palmitate into structural and oncogenic glycerophospholipids, sphingolipids, and ether lipids. We also find that fatty acid incorporation into oxidative pathways is reduced in aggressive human cancer cells, and instead shunted into pathways for generating structural and signaling lipids. Our results demonstrate that cancer cells do not solely rely on de novo lipogenesis, but also utilize exogenous fatty acids for generating lipids required for proliferation and protumorigenic lipid signaling. This article is part of a special issue entitled Lipid Metabolism in Cancer. © 2013.

Enhancement of microbial 2,4,6-trinitrotoluene transformation with increased toxicity by exogenous nutrient amendment.

PubMed

Liang, Shih-Hsiung; Hsu, Duen-Wei; Lin, Chia-Ying; Kao, Chih-Ming; Huang, Da-Ji; Chien, Chih-Ching; Chen, Ssu-Ching; Tsai, Isheng Jason; Chen, Chien-Cheng

2017-04-01

In this study, the bacterial strain Citrobacter youngae strain E4 was isolated from 2,4,6-trinitrotoluene (TNT)-contaminated soil and used to assess the capacity of TNT transformation with/without exogenous nutrient amendments. C. youngae E4 poorly degraded TNT without an exogenous amino nitrogen source, whereas the addition of an amino nitrogen source considerably increased the efficacy of TNT transformation in a dose-dependent manner. The enhanced TNT transformation of C. youngae E4 was mediated by increased cell growth and up-regulation of TNT nitroreductases, including NemA, NfsA and NfsB. This result indicates that the increase in TNT transformation by C. youngae E4 via nitrogen nutrient stimulation is a cometabolism process. Consistently, TNT transformation was effectively enhanced when C. youngae E4 was subjected to a TNT-contaminated soil slurry in the presence of an exogenous amino nitrogen amendment. Thus, effective enhancement of TNT transformation via the coordinated inoculation of the nutrient-responsive C. youngae E4 and an exogenous nitrogen amendment might be applicable for the remediation of TNT-contaminated soil. Although the TNT transformation was significantly enhanced by C. youngae E4 in concert with biostimulation, the 96-h LC50 value of the TNT transformation product mixture on the aquatic invertebrate Tigriopus japonicas was higher than the LC50 value of TNT alone. Our results suggest that exogenous nutrient amendment can enhance microbial TNT transformation; however, additional detoxification processes may be needed due to the increased toxicity after reduced TNT transformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming performance

PubMed Central

Omlin, Teye; Langevin, Karolanne

2014-01-01

Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 μmol·kg−1·min−1. This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport. PMID:25121611

Effect of Straw Amendment on Soil Zn Availability and Ageing of Exogenous Water-Soluble Zn Applied to Calcareous Soil.

PubMed

Chen, Yanlong; Cui, Juan; Tian, Xiaohong; Zhao, Aiqing; Li, Meng; Wang, Shaoxia; Li, Xiushaung; Jia, Zhou; Liu, Ke

2017-01-01

Organic matter plays a key role in availability and transformation of soil Zn (zinc), which greatly controls Zn concentrations in cereal grains and human Zn nutrition level. Accordingly, soils homogenized with the wheat straw (0, 12 g straw kg-1) and Zn fertilizer (0, 7 mg Zn kg-1) were buried and incubated in the field over 210 days to explore the response of soil Zn availability and the ageing of exogenous Zn to straw addition. Results indicated that adding straw alone scarcely affected soil DTPA-Zn concentration and Zn fractions because of the low Zn concentration of wheat straw and the high soil pH, and large clay and calcium carbonate contents. However, adding exogenous Zn plus straw increased the DTPA-Zn abundance by about 5-fold and had the similar results to adding exogenous Zn alone, corresponding to the increased Zn fraction loosely bounded to organic matter, which had a more dominant presence in Zn reaction than soil other constituents such as carbonate and minerals in calcareous soil. The higher relative amount of ineffective Zn (~50%) after water soluble Zn addition also occurred, and at the days of 120-165 and 180-210when the natural temperature and rainfall changed mildly, the ageing process of exogenous Zn over time was well evaluated by the diffusion equation, respectively. Consequently, combining crop residues with exogenous water soluble Zn application is promising strategy to maximize the availability of Zn in calcareous soil, but the higher ageing rate of Zn caused by the higher Zn mobility should be considered.

On the relative contributions of multisensory integration and crossmodal exogenous spatial attention to multisensory response enhancement.

PubMed

Van der Stoep, N; Spence, C; Nijboer, T C W; Van der Stigchel, S

2015-11-01

Two processes that can give rise to multisensory response enhancement (MRE) are multisensory integration (MSI) and crossmodal exogenous spatial attention. It is, however, currently unclear what the relative contribution of each of these is to MRE. We investigated this issue using two tasks that are generally assumed to measure MSI (a redundant target effect task) and crossmodal exogenous spatial attention (a spatial cueing task). One block of trials consisted of unimodal auditory and visual targets designed to provide a unimodal baseline. In two other blocks of trials, the participants were presented with spatially and temporally aligned and misaligned audiovisual (AV) targets (0, 50, 100, and 200ms SOA). In the integration block, the participants were instructed to respond to the onset of the first target stimulus that they detected (A or V). The instruction for the cueing block was to respond only to the onset of the visual targets. The targets could appear at one of three locations: left, center, and right. The participants were instructed to respond only to lateral targets. The results indicated that MRE was caused by MSI at 0ms SOA. At 50ms SOA, both crossmodal exogenous spatial attention and MSI contributed to the observed MRE, whereas the MRE observed at the 100 and 200ms SOAs was attributable to crossmodal exogenous spatial attention, alerting, and temporal preparation. These results therefore suggest that there may be a temporal window in which both MSI and exogenous crossmodal spatial attention can contribute to multisensory response enhancement. Copyright © 2015 Elsevier B.V. All rights reserved.

Exogenous NAD+ decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy

PubMed Central

Zhu, Ying; Zhao, Ke-ke; Tong, Yao; Zhou, Ya-li; Wang, Yi-xiao; Zhao, Pei-quan; Wang, Zhao-yang

2016-01-01

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD+) administration significantly blocked RPE cell death induced by 300 μM H2O2. Further investigation showed that H2O2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD+ administration significantly decreased intracellular and intranuclear ROS levels in H2O2-treated RPE cells. In addition, NAD+ administration to H2O2-treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD+ administration up-regulated autophagy in the H2O2-treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD+ against H2O2-induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD+ administration suppresses H2O2-induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD+ administration might be potential value for the treatment of AMD. PMID:27240523

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191

Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews.

PubMed

Onasanya, Oluwadamilola; Iyer, Geetha; Lucas, Eleanor; Lin, Dora; Singh, Sonal; Alexander, G Caleb

2016-11-01

Given the conflicting evidence regarding the association between exogenous testosterone and cardiovascular events, we systematically assessed published systematic reviews for evidence of the association between exogenous testosterone and cardiovascular events. We searched PubMed, MEDLINE, Embase, Cochrane Collaboration Clinical Trials, ClinicalTrials.gov, and the US Food and Drug Administration website for systematic reviews of randomised controlled trials published up to July 19, 2016. Two independent reviewers screened 954 full texts from 29 335 abstracts to identify systematic reviews of randomised controlled trials in which the cardiovascular effects of exogenous testosterone on men aged 18 years or older were examined. We extracted data for study characteristics, analytic methods, and key findings, and applied the AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklist to assess methodological quality of each review. Our primary outcome measure was the direction and magnitude of association between exogenous testosterone and cardiovascular events. We identified seven reviews and meta-analyses, which had substantial clinical heterogeneity, differing statistical methods, and variable methodological quality and quality of data abstraction. AMSTAR scores ranged from 3 to 9 out of 11. Six systematic reviews that each included a meta-analysis showed no significant association between exogenous testosterone and cardiovascular events, with summary estimates ranging from 1·07 to 1·82 and imprecise confidence intervals. Two of these six meta-analyses showed increased risk in subgroup analyses of oral testosterone and men aged 65 years or older during their first treatment year. One meta-analysis showed a significant association between exogenous testosterone and cardiovascular events, in men aged 18 years or older generally, with a summary estimate of 1·54 (95% CI 1·09-2·18). Our optimal information size analysis showed that any randomised controlled trial aiming to detect a true difference in cardiovascular risk between treatment groups receiving exogenous testosterone and their controls (with a two-sided p value of 0·05 and a power of 80%) would require at least 17 664 participants in each trial group. Therefore, given the challenge of adequately powering clinical trials for rare outcomes, rigorous observational studies are needed to clarify the association between testosterone-replacement therapy and major adverse cardiovascular outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estrogen-induced myelotoxicity in dogs: A review

PubMed Central

Sontas, Hasan B.; Dokuzeylu, Banu; Turna, Ozge; Ekici, Hayri

2009-01-01

Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the patients, the diagnosis, and the treatment options in the dog. PMID:20046604

Whole rock major element chemistry of KREEP basalt clasts in lunar breccia 15205: Implications for the petrogenesis of volcanic KREEP basalts

NASA Technical Reports Server (NTRS)

Vetter, Scott K.; Shervais, John W.

1993-01-01

KREEP basalts are a major component of soils and regolith at the Apollo 15 site. Their origin is controversial: both endogenous (volcanic) and exogenous (impact melt) processes have been proposed, but it is now generally agreed that KREEP basalts are volcanic rocks derived from the nearby Apennine Bench formation. Because most pristine KREEP basalts are found only as small clasts in polymict lunar breccias, reliable chemical data are scarce. The primary aim of this study is to characterize the range in chemical composition of pristine KREEP basalt, and to use these data to decipher the petrogenesis of these unique volcanic rocks.

Melatonin plays a protective role in postburn rodent gut pathophysiology.

PubMed

Al-Ghoul, Walid M; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

2010-05-17

Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 micromole/kg), but not 1.86 mg/kg (8 micromole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 micromole/kg) significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation.

Melatonin Plays a Protective Role in Postburn Rodent Gut Pathophysiology

PubMed Central

Al-Ghoul, Walid M.; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

2010-01-01

Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 μmole/kg), but not 1.86 mg/kg (8 μmole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin supplementation on postburn gut mucosa barrier inflammatory profiles. Here, our results revealed that daily postburn intraperitoneal melatonin administration at a dose of 1.86 mg/kg (8 μmole/kg) significantly suppressed both neutrophil infiltration and tyrosine nitrosylation as revealed by Gr-1 and nitrotyrosine immunohistochemistry, respectively. In conclusion, our results provide support for high mesenteric melatonin levels and dynamic de novo gut melatonin production, both of which increase endogenously in response to major thermal injury, but appear to fall short of abrogating the excessive postburn hyper-inflammation. Moreover, supplementation by exogenous melatonin significantly suppresses gut inflammation, thus confirming that melatonin is protective against postburn inflammation. PMID:20567497

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.

PubMed

Patten, Ian S; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R; Rhee, Julie S; Mitchell, John; Mahmood, Feroze; Hess, Philip; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S Ananth; Arany, Zoltan

2012-05-09

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

PubMed Central

Patten, Ian S.; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R.; Rhee, Julie S.; Mitchell, John; Mahmood, Feroze; Hess, Phil; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D.; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S. Ananth; Arany, Zoltan

2012-01-01

Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. PMID:22596155

Clinical breath analysis: Discriminating between human endogenous compounds and exogenous (environmental) chemical confounders

EPA Science Inventory

Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous ...

Isolating Exogenous and Endogenous Modes of Temporal Attention

ERIC Educational Resources Information Center

Lawrence, Michael A.; Klein, Raymond M.

2013-01-01

The differential allocation of information processing resources over time, here termed "temporal attention," may be achieved by relatively automatic "exogenous" or controlled "endogenous" mechanisms. Over 100 years of research has confounded these theoretically distinct dimensions of temporal attention. The current…

Minnesota urban partnership agreement national evaluation : exogenous factors test plan.

DOT National Transportation Integrated Search

2009-11-17

This report presents the exogenous factors test plan for the national evaluation of the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reduc...

San Francisco urban partnership agreement, national evaluation : exogenous factors test plan.

DOT National Transportation Integrated Search

2011-06-01

This report presents the test plan for collecting and analyzing exogenous factors data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects...

The role of exogenic factors in the formation of the lunar surface

NASA Technical Reports Server (NTRS)

Florenskiy, K. P.; Bazilevskiy, A. T.; Ivanov, A. V.

1977-01-01

The formation of the surface of planetary bodies is determined by the interaction of endogenic and exogenic forces. Clarification of the mutual role of these forces is one of the most important trends in the geological sciences.

Prostaglandin release from in vitro guinea-pig gallbladder.

PubMed

Booker, M L; LaMorte, W W

1983-02-01

In order to study prostaglandin release from guinea pig gallbladder, full thickness tissue sections were incubated for one hour in Krebs solution. Extraction and two dimensional chromatography of incubation media obtained in the presence of radio-labelled arachidonic acid demonstrated the presence of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. These results were supported by radioimmunoassay of incubations conducted in the absence of exogenous arachidonate and in the presence of varying concentrations of unlabelled exogenous arachidonate. The previously reported predominance of PGE2 was only seen at high concentrations of exogenous arachidonate.

The study of efficiency of endogenous and exogenous preventive methods of tooth enamel remineralisation by FTIR microscopy using synchrotron radiation

NASA Astrophysics Data System (ADS)

Goloshchapov, D. L.; Kashkarov, V. M.; Seredin, P. V.; Ippolitov, Y. A.; Plotnikova, Y. A.; Bambery, K.

2016-08-01

The efficiency carious preventive methods was detected with the use of equipment for IR-spectromicroscopy and high-intensive synchrotron radiation. The results of the experiment are indicative of the use of exogenous caries prevention alone (use of a toothpaste) being inadequate in saturating hard dental tissues by mineral groups and, thus, keeping teeth healthy, as this method is only short-lived. The use of endogenous methods (mineral tablets based on calcium glycerophosphate) in combination with exogenous prevention enhances prevention as part of remineralisation of dental tissues.

The effect of an exogenous magnetic field on neural coding in deep spiking neural networks.

PubMed

Guo, Lei; Zhang, Wei; Zhang, Jialei

2018-01-01

A ten-layer feed forward network is constructed in the presence of an exogenous alternating magnetic field. Specifically, our results indicate that for rate coding, the firing rate is significantly increased in the presence of an exogenous alternating magnetic field and particularly with increasing enhancement of the alternating magnetic field amplitude. For temporal coding, the interspike intervals of the spiking sequence are decreased and the distribution of the interspike intervals of the spiking sequence tends to be uniform in the presence of alternating magnetic field.

Mechanisms of callose deposition in rice regulated by exogenous abscisic acid and its involvement in rice resistance to Nilaparvata lugens Stål (Hemiptera: Delphacidae).

PubMed

Liu, Jinglan; Du, Haitao; Ding, Xu; Zhou, Yaodong; Xie, Pengfei; Wu, Jincai

2017-12-01

Callose is a plant cell wall polysaccharide controlled by β-1,3-glucanase and synthase. Abscisic acid (ABA) is an important plant hormone. Exogenous ABA promotes rice resistance to pests. Whether exogenous ABA could reduce the decline in rice yield after brown planthopper (Nilaparvata lugens Stål; BPH) feeding is an important question, however, the mechanisms behind rice resistance induced by ABA remain obscure. Electronic penetration graph (EPG) recording indicated a significant increase in rice resistance to BPH, and the number of BPH eggs decreased significantly upon application of exogenous ABA. As the concentration of ABA increased, the reduction in rice yield decreased significantly after BPH feeding. Further studies showed that β-1,3-glucanase activity was significantly lower, but synthase activity was higher after ABA treatment than in controls. Our results demonstrated that exogenous ABA suppressed β-1,3-glucanase and induced synthase activity, and promoted callose deposition. This is an important defense mechanism that prevents BPH from ingesting phloem sap. These studies provide support for an insect-resistance mechanism after ABA treatment and provide a reference for the integrated management of other piercing-sucking pests. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The combined effects of exogenous and endogenous variability on the spatial distribution of ant communities in a forested ecosystem (Hymenoptera: Formicidae).

PubMed

Yitbarek, Senay; Vandermeer, John H; Allen, David

2011-10-01

Spatial patterns observed in ecosystems have traditionally been attributed to exogenous processes. Recently, ecologists have found that endogenous processes also have the potential to create spatial patterns. Yet, relatively few studies have attempted to examine the combined effects of exogenous and endogenous processes on the distribution of organisms across spatial and temporal scales. Here we aim to do this, by investigating whether spatial patterns of under-story tree species at a large spatial scale (18 ha) influences the spatial patterns of ground foraging ant species at a much smaller spatial scale (20 m by 20 m). At the regional scale, exogenous processes (under-story tree community) had a strong effect on the spatial patterns in the ground-foraging ant community. We found significantly more Camponotus noveboracensis, Formica subsericae, and Lasius alienus species in black cherry (Prunis serotine Ehrh.) habitats. In witch-hazel (Hamamelis virginiana L.) habitats, we similarly found significantly more Myrmica americana, Formica fusca, and Formica subsericae. At smaller spatial scales, we observed the emergence of mosaic ant patches changing rapidly in space and time. Our study reveals that spatial patterns are the result of both exogenous and endogenous forces, operating at distinct scales.

Proteomic Analysis Reveals the Positive Effect of Exogenous Spermidine in Tomato Seedlings' Response to High-Temperature Stress

PubMed Central

Sang, Qinqin; Shan, Xi; An, Yahong; Shu, Sheng; Sun, Jin; Guo, Shirong

2017-01-01

Polyamines are phytohormones that regulate plant growth and development as well as the response to environmental stresses. To evaluate their functions in high-temperature stress responses, the effects of exogenous spermidine (Spd) were determined in tomato leaves using two-dimensional electrophoresis and MALDI-TOF/TOF MS. A total of 67 differentially expressed proteins were identified in response to high-temperature stress and/or exogenous Spd, which were grouped into different categories according to biological processes. The four largest categories included proteins involved in photosynthesis (27%), cell rescue, and defense (24%), protein synthesis, folding and degradation (22%), and energy and metabolism (13%). Exogenous Spd up-regulated most identified proteins involved in photosynthesis, implying an enhancement in photosynthetic capacity. Meanwhile, physiological analysis showed that Spd could improve net photosynthetic rate and the biomass accumulation. Moreover, an increased high-temperature stress tolerance by exogenous Spd would contribute to the higher expressions of proteins involved in cell rescue and defense, and Spd regulated the antioxidant enzymes activities and related genes expression in tomato seedlings exposed to high temperature. Taken together, these findings provide a better understanding of the Spd-induced high-temperature resistance by proteomic approaches, providing valuable insight into improving the high-temperature stress tolerance in the global warming epoch. PMID:28220137

Proteomic Analysis Reveals the Positive Effect of Exogenous Spermidine in Tomato Seedlings' Response to High-Temperature Stress.

PubMed

Sang, Qinqin; Shan, Xi; An, Yahong; Shu, Sheng; Sun, Jin; Guo, Shirong

2017-01-01

Polyamines are phytohormones that regulate plant growth and development as well as the response to environmental stresses. To evaluate their functions in high-temperature stress responses, the effects of exogenous spermidine (Spd) were determined in tomato leaves using two-dimensional electrophoresis and MALDI-TOF/TOF MS. A total of 67 differentially expressed proteins were identified in response to high-temperature stress and/or exogenous Spd, which were grouped into different categories according to biological processes. The four largest categories included proteins involved in photosynthesis (27%), cell rescue, and defense (24%), protein synthesis, folding and degradation (22%), and energy and metabolism (13%). Exogenous Spd up-regulated most identified proteins involved in photosynthesis, implying an enhancement in photosynthetic capacity. Meanwhile, physiological analysis showed that Spd could improve net photosynthetic rate and the biomass accumulation. Moreover, an increased high-temperature stress tolerance by exogenous Spd would contribute to the higher expressions of proteins involved in cell rescue and defense, and Spd regulated the antioxidant enzymes activities and related genes expression in tomato seedlings exposed to high temperature. Taken together, these findings provide a better understanding of the Spd-induced high-temperature resistance by proteomic approaches, providing valuable insight into improving the high-temperature stress tolerance in the global warming epoch.

A combination of He-Ne laser irradiation and exogenous NO application efficiently protect wheat seedling from oxidative stress caused by elevated UV-B stress.

PubMed

Li, Yongfeng; Gao, Limei; Han, Rong

2016-12-01

The elevated ultraviolet-B (UV-B) stress induces the accumulation of a variety of intracellular reactive oxygen species (ROS), which seems to cause oxidative stress for plants. To date, very little work has been done to evaluate the biological effects of a combined treatment with He-Ne laser irradiation and exogenous nitric oxide (NO) application on oxidative stress resulting from UV-B radiation. Thus, our study investigated the effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative damages in wheat seedlings under elevated UV-B stress. Our data showed that the reductions in ROS levels, membrane damage parameters, while the increments in antioxidant contents and antioxidant enzyme activity caused by a combination with He-Ne laser and exogenous NO treatment were greater than those of each individual treatment. Furthermore, these treatments had a similar effect on transcriptional activities of plant antioxidant enzymes. This implied that the protective effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative stress resulting from UV-B radiation was more efficient than each individual treatment with He-Ne laser or NO molecule. Our findings might provide beneficial theoretical references for identifying some effective new pathways for plant UV-B protection.