Frequency-dependent variation in mimetic fidelity in an intraspecific mimicry system

PubMed Central

Iserbyt, Arne; Bots, Jessica; Van Dongen, Stefan; Ting, Janice J.; Van Gossum, Hans; Sherratt, Thomas N.

2011-01-01

Contemporary theory predicts that the degree of mimetic similarity of mimics towards their model should increase as the mimic/model ratio increases. Thus, when the mimic/model ratio is high, then the mimic has to resemble the model very closely to still gain protection from the signal receiver. To date, empirical evidence of this effect is limited to a single example where mimicry occurs between species. Here, for the first time, we test whether mimetic fidelity varies with mimic/model ratios in an intraspecific mimicry system, in which signal receivers are the same species as the mimics and models. To this end, we studied a polymorphic damselfly with a single male phenotype and two female morphs, in which one morph resembles the male phenotype while the other does not. Phenotypic similarity of males to both female morphs was quantified using morphometric data for multiple populations with varying mimic/model ratios repeated over a 3 year period. Our results demonstrate that male-like females were overall closer in size to males than the other female morph. Furthermore, the extent of morphological similarity between male-like females and males, measured as Mahalanobis distances, was frequency-dependent in the direction predicted. Hence, this study provides direct quantitative support for the prediction that the mimetic similarity of mimics to their models increases as the mimic/model ratio increases. We suggest that the phenomenon may be widespread in a range of mimicry systems. PMID:21367784

Stroke mimic diagnoses presenting to a hyperacute stroke unit.

PubMed

Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

2016-10-01

Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

Mobile Motion Capture--MiMiC.

PubMed

Harbert, Simeon D; Jaiswal, Tushar; Harley, Linda R; Vaughn, Tyler W; Baranak, Andrew S

2013-01-01

The low cost, simple, robust, mobile, and easy to use Mobile Motion Capture (MiMiC) system is presented and the constraints which guided the design of MiMiC are discussed. The MiMiC Android application allows motion data to be captured from kinematic modules such as Shimmer 2r sensors over Bluetooth. MiMiC is cost effective and can be used for an entire day in a person's daily routine without being intrusive. MiMiC is a flexible motion capture system which can be used for many applications including fall detection, detection of fatigue in industry workers, and analysis of individuals' work patterns in various environments.

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF.

PubMed

Cheng, Ying; Shao, Can; Lathrop, Quinn N

2016-02-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.

The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

PubMed Central

Cheng, Ying; Shao, Can; Lathrop, Quinn N.

2015-01-01

Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

PubMed

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

2013-11-28

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1-8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites.

Reverse-Bumpy-Ball-Type-Nanoreactor-Loaded Nylon Membranes as Peroxidase-Mimic Membrane Reactors for a Colorimetric Assay for H₂O₂.

PubMed

Tong, Ying; Jiao, Xiangyu; Yang, Hankun; Wen, Yongqiang; Su, Lei; Zhang, Xueji

2016-04-01

Herein we report for the first time fabrication of reverse bumpy ball (RBB)-type-nanoreactor-based flexible peroxidase-mimic membrane reactors (MRs). The RBB-type nanoreactors with gold nanoparticles embedded in the inner walls of carbon shells were loaded on nylon membranes through a facile filtration approach. The as-prepared flexible catalytic membrane was studied as a peroxidase-mimic MR. It was found that the obtained peroxidase-mimic MR could exhibit several advantages over natural enzymes, such as facile and good recyclability, long-term stability and easy storage. Moreover, the RBB NS-modified nylon MRs as a peroxidase mimic provide a useful colorimetric assay for H₂O₂.

Prey from the eyes of predators: Color discriminability of aposematic and mimetic butterflies from an avian visual perspective.

PubMed

Su, Shiyu; Lim, Matthew; Kunte, Krushnamegh

2015-11-01

Predation exerts strong selection on mimetic butterfly wing color patterns, which also serve other functions such as sexual selection. Therefore, specific selection pressures may affect the sexes and signal components differentially. We tested three predictions about the evolution of mimetic resemblance by comparing wing coloration of aposematic butterflies and their Batesian mimics: (a) females gain greater mimetic advantage than males and therefore are better mimics, (b) due to intersexual genetic correlations, sexually monomorphic mimics are better mimics than female-limited mimics, and (c) mimetic resemblance is better on the dorsal wing surface that is visible to predators in flight. Using a physiological model of avian color vision, we quantified mimetic resemblance from predators' perspective, which showed that female butterflies were better mimics than males. Mimetic resemblance in female-limited mimics was comparable to that in sexually monomorphic mimics, suggesting that intersexual genetic correlations did not constrain adaptive response to selection for female-limited mimicry. Mimetic resemblance on the ventral wing surface was better than that on the dorsal wing surface, implying stronger natural and sexual selection on ventral and dorsal surfaces, respectively. These results suggest that mimetic resemblance in butterfly mimicry rings has evolved under various selective pressures acting in a sex- and wing surface-specific manner. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Characterization and mapping of complementary lesion-mimic genes lm1 and lm2 in common wheat.

PubMed

Yao, Qin; Zhou, Ronghua; Fu, Tihua; Wu, Weiren; Zhu, Zhendong; Li, Aili; Jia, Jizeng

2009-10-01

A lesion-mimic phenotype appeared in a segregating population of common wheat cross Yanzhan 1/Zaosui 30. The parents had non-lesion normal phenotypes. Shading treatment and histochemical analyses showed that the lesions were caused by light-dependent cell death and were not associated with pathogens. Studies over two cropping seasons showed that some lines with more highly expressed lesion-mimic phenotypes exhibited significantly lower grain yields than those with the normal phenotype, but there were no significant effects in the lines with weakly expressed lesion-mimic phenotypes. Among yield traits, one-thousand grain weight was the most affected by lesion-mimic phenotypes. Genetic analysis indicated that this was a novel type of lesion mimic, which was caused by interaction of recessive genes derived from each parent. The lm1 (lesion mimic 1) locus from Zaosui 30 was flanked by microsatellite markers Xwmc674 and Xbarc133/Xbarc147 on chromosome 3BS, at genetic distances of 1.2 and 3.8 cM, respectively, whereas lm2 from Yanzhan 1 was mapped between microsatellite markers Xgwm513 and Xksum154 on chromosome 4BL, at genetic distances of 1.5 and 3 cM, respectively. The linked microsatellite makers identified in this study might be useful for evaluating whether potential parents with normal phenotype are carriers of lesion-mimic alleles.

Open-access MIMIC-II database for intensive care research.

PubMed

Lee, Joon; Scott, Daniel J; Villarroel, Mauricio; Clifford, Gari D; Saeed, Mohammed; Mark, Roger G

2011-01-01

The critical state of intensive care unit (ICU) patients demands close monitoring, and as a result a large volume of multi-parameter data is collected continuously. This represents a unique opportunity for researchers interested in clinical data mining. We sought to foster a more transparent and efficient intensive care research community by building a publicly available ICU database, namely Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II). The data harnessed in MIMIC-II were collected from the ICUs of Beth Israel Deaconess Medical Center from 2001 to 2008 and represent 26,870 adult hospital admissions (version 2.6). MIMIC-II consists of two major components: clinical data and physiological waveforms. The clinical data, which include patient demographics, intravenous medication drip rates, and laboratory test results, were organized into a relational database. The physiological waveforms, including 125 Hz signals recorded at bedside and corresponding vital signs, were stored in an open-source format. MIMIC-II data were also deidentified in order to remove protected health information. Any interested researcher can gain access to MIMIC-II free of charge after signing a data use agreement and completing human subjects training. MIMIC-II can support a wide variety of research studies, ranging from the development of clinical decision support algorithms to retrospective clinical studies. We anticipate that MIMIC-II will be an invaluable resource for intensive care research by stimulating fair comparisons among different studies.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

PubMed

Egi, H; Hattori, M; Tokunaga, M; Suzuki, T; Kawaguchi, K; Sawada, H; Ohdan, H

2013-01-01

The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery. © 2013 S. Karger AG, Basel.

Process mining in oncology using the MIMIC-III dataset

NASA Astrophysics Data System (ADS)

Prima Kurniati, Angelina; Hall, Geoff; Hogg, David; Johnson, Owen

2018-03-01

Process mining is a data analytics approach to discover and analyse process models based on the real activities captured in information systems. There is a growing body of literature on process mining in healthcare, including oncology, the study of cancer. In earlier work we found 37 peer-reviewed papers describing process mining research in oncology with a regular complaint being the limited availability and accessibility of datasets with suitable information for process mining. Publicly available datasets are one option and this paper describes the potential to use MIMIC-III, for process mining in oncology. MIMIC-III is a large open access dataset of de-identified patient records. There are 134 publications listed as using the MIMIC dataset, but none of them have used process mining. The MIMIC-III dataset has 16 event tables which are potentially useful for process mining and this paper demonstrates the opportunities to use MIMIC-III for process mining in oncology. Our research applied the L* lifecycle method to provide a worked example showing how process mining can be used to analyse cancer pathways. The results and data quality limitations are discussed along with opportunities for further work and reflection on the value of MIMIC-III for reproducible process mining research.

Studies of Altered Response to Infection Induced by Severe Injury.

DTIC Science & Technology

1994-11-15

quantitation of original specific RNA was determined by comparison of target and MIMIC band intensities and were standardized by G3PDH quantities. 4 RESULTS... housekeeping gene G 3PDH (Fig. 1). We compared the amount of mRNA present after 3 hours of stimulation to the amount of bioactivity present after 16 hours...Is$ mimic concelntration l PCR with G3PDH Primers ( G3PDH ) PCR Products Gel MIMIC -~ Attomoie MIMIC 100 10 1 0.1 SDensitometry Reading I Graphing and

Live Cell Imaging Reveals Differential Modifications to Cytoplasmic Dynein Properties by Phospho- and Dephospho-mimic Mutations of the Intermediate Chain 2C S84

PubMed Central

Blasier, Kiev R.; Humsi, Michael K.; Ha, Junghoon; Ross, Mitchell W.; Smiley, W. Russell; Inamdar, Nirja A.; Mitchell, David J.; Lo, Kevin W.-H.; Pfister, K. Kevin

2014-01-01

Cytoplasmic dynein is a multi-subunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC) which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells and the functional significance of phosphorylation on IC-2C serine 84 was investigated using live cell imaging of fluorescent protein-tagged wild type IC-2C (WT) and phospho- and dephospho-mimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephospho-mimic mutant IC-2C S84A had greater co-localization with mitochondria than IC-2C wild-type (WT) or the phospho-mimic mutant IC-2C S84D. The dephospho-mimic mutant IC-2C S84A was also more likely to be motile than the phospho-mimic mutant IC-2C S84D or IC-2C WT. In contrast, the phospho-mimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phospho-mimic IC-2C S84D was also as likely as IC-2C WT to co-localize with mitochondria. Both the S84D phospho- and S84A, dephospho-mimic mutants were found to be capable of microtubule minus end directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties. PMID:24798412

Target mimics: an embedded layer of microRNA-involved gene regulatory networks in plants.

PubMed

Meng, Yijun; Shao, Chaogang; Wang, Huizhong; Jin, Yongfeng

2012-05-21

MicroRNAs (miRNAs) play an essential role in gene regulation in plants. At the same time, the expression of miRNA genes is also tightly controlled. Recently, a novel mechanism called "target mimicry" was discovered, providing another layer for modulating miRNA activities. However, except for the artificial target mimics manipulated for functional studies on certain miRNA genes, only one example, IPS1 (Induced by Phosphate Starvation 1)-miR399 was experimentally confirmed in planta. To date, few analyses for comprehensive identification of natural target mimics have been performed in plants. Thus, limited evidences are available to provide detailed information for interrogating the questionable issue whether target mimicry was widespread in planta, and implicated in certain biological processes. In this study, genome-wide computational prediction of endogenous miRNA mimics was performed in Arabidopsis and rice, and dozens of target mimics were identified. In contrast to a recent report, the densities of target mimic sites were found to be much higher within the untranslated regions (UTRs) when compared to those within the coding sequences (CDSs) in both plants. Some novel sequence characteristics were observed for the miRNAs that were potentially regulated by the target mimics. GO (Gene Ontology) term enrichment analysis revealed some functional insights into the predicted mimics. After degradome sequencing data-based identification of miRNA targets, the regulatory networks constituted by target mimics, miRNAs and their downstream targets were constructed, and some intriguing subnetworks were further exploited. These results together suggest that target mimicry may be widely implicated in regulating miRNA activities in planta, and we hope this study could expand the current understanding of miRNA-involved regulatory networks.

Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

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

Rajagopalan, Raghavan

The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling studymore » revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.« less

Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries.

PubMed

Mulder, Gwenn E; Quarles van Ufford, H Linda C; van Ameijde, Jeroen; Brouwer, Arwin J; Kruijtzer, John A W; Liskamp, Rob M J

2013-04-28

A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of protein-protein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide-alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

PubMed

Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

2016-01-01

We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells

PubMed Central

Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

2016-01-01

We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy. PMID:27575372

A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

PubMed

Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

2016-04-13

Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS)☟

PubMed Central

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M.; Ioerger, Thomas R.; Burgess, Kevin

2013-01-01

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, “minimalist helical mimics”. It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i+4, i+7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i+3, i+7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds;(iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain “triads” in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the “side-chain correspondences” (eg i, i+4, i+7 or i, i+3, i+4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1 – 8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites. PMID:24121516

The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study.

PubMed

Jamali, Jamshid; Ayatollahi, Seyyed Mohammad Taghi; Jafari, Peyman

2017-01-01

Evaluating measurement equivalence (also known as differential item functioning (DIF)) is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC) model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study

PubMed Central

Jafari, Peyman

2017-01-01

Evaluating measurement equivalence (also known as differential item functioning (DIF)) is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC) model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small. PMID:28713828

Shape-based approach for the estimation of individual facial mimics in craniofacial surgery planning

NASA Astrophysics Data System (ADS)

Gladilin, Evgeny; Zachow, Stefan; Deuflhard, Peter; Hege, Hans-Christian

2002-05-01

Besides the static soft tissue prediction, the estimation of basic facial emotion expressions is another important criterion for the evaluation of craniofacial surgery planning. For a realistic simulation of facial mimics, an adequate biomechanical model of soft tissue including the mimic musculature is needed. In this work, we present an approach for the modeling of arbitrarily shaped muscles and the estimation of basic individual facial mimics, which is based on the geometrical model derived from the individual tomographic data and the general finite element modeling of soft tissue biomechanics.

Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

PubMed Central

Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

2018-01-01

There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, p<0.05). Mimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug candidates. PMID:29507615

Effects of hydrophobic helix length and side chain chemistry on biomimicry in peptoid analogues of SP-C.

PubMed

Brown, Nathan J; Wu, Cindy W; Seurynck-Servoss, Shannon L; Barron, Annelise E

2008-02-12

The hydrophobic proteins of lung surfactant (LS), SP-B and SP-C, are critical constituents of an effective surfactant replacement therapy for the treatment of respiratory distress syndrome. Because of concerns and difficulties associated with animal-derived surfactants, recent investigations have focused on the creation of synthetic analogues of the LS proteins. However, creating an accurate mimic of SP-C that retains its biophysical surface activity is extraordinarily challenging given the lipopeptide's extreme hydrophobicity and propensity to misfold and aggregate. One successful approach that overcomes these difficulties is the use of poly-N-substituted glycines, or peptoids, to mimic SP-C. To develop a non-natural, bioactive mimic of SP-C and to investigate the effects of side chain chemistry and length of the helical hydrophobic region, we synthesized, purified, and performed in vitro testing of two classes of peptoid SP-C mimics: those having a rigid alpha-chiral aromatic helix and those having a biomimetic alpha-chiral aliphatic helix. The length of the two classes of mimics was also systematically altered. Circular dichroism spectroscopy gave evidence that all of the peptoid-based mimics studied here emulated SP-C's secondary structure, forming stable helical structures in solution. Langmuir-Wilhelmy surface balance, fluorescence microscopy, and pulsating bubble surfactometry experiments provide evidence that the aromatic-based SP-C peptoid mimics, in conjunction with a synthetic lipid mixture, have superior surface activity and biomimetic film morphology in comparison to the aliphatic-based mimics and that there is an increase in surface activity corresponding to increasing helical length.

Testing Measurement Invariance Using MIMIC: Likelihood Ratio Test with a Critical Value Adjustment

ERIC Educational Resources Information Center

Kim, Eun Sook; Yoon, Myeongsun; Lee, Taehun

2012-01-01

Multiple-indicators multiple-causes (MIMIC) modeling is often used to test a latent group mean difference while assuming the equivalence of factor loadings and intercepts over groups. However, this study demonstrated that MIMIC was insensitive to the presence of factor loading noninvariance, which implies that factor loading invariance should be…

MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring

NASA Technical Reports Server (NTRS)

Saeed, M.; Lieu, C.; Raber, G.; Mark, R. G.

2002-01-01

Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

Multiple indicators, multiple causes measurement error models

DOE PAGES

Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; ...

2014-06-25

Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this study are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methodsmore » for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. Finally, as a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.« less

Multiple Indicators, Multiple Causes Measurement Error Models

PubMed Central

Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.; Carroll, Raymond J.

2014-01-01

Multiple Indicators, Multiple Causes Models (MIMIC) are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times however when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are: (1) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model, (2) to develop likelihood based estimation methods for the MIMIC ME model, (3) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. As a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure. PMID:24962535

Multiple indicators, multiple causes measurement error models

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

Tekwe, Carmen D.; Carter, Randy L.; Cullings, Harry M.

Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this study are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methodsmore » for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia. Finally, as a by-product of our work, we also obtain a data-driven estimate of the variance of the classical measurement error associated with an estimate of the amount of radiation dose received by atomic bomb survivors at the time of their exposure.« less

Passenger strand loading in overexpression experiments using microRNA mimics.

PubMed

Søkilde, Rolf; Newie, Inga; Persson, Helena; Borg, Åke; Rovira, Carlos

2015-01-01

MicroRNAs (miRNAs) are important regulators of gene function and manipulation of miRNAs is a central component of basic research. Modulation of gene expression by miRNA gain-of-function can be based on different approaches including transfection with miRNA mimics; artificial, chemically modified miRNA-like small RNAs. These molecules are intended to mimic the function of a miRNA guide strand while bypassing the maturation steps of endogenous miRNAs. Due to easy accessibility through commercial providers this approach has gained popularity, and accuracy is often assumed without prior independent testing. Our in silico analysis of over-represented sequence motifs in microarray expression data and sequencing of AGO-associated small RNAs indicate, however, that miRNA mimics may be associated with considerable side-effects due to the unwanted activity of the miRNA mimic complementary strand.

The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.

PubMed

Winata, Patrick; Williams, Marissa; McGowan, Eileen; Nassif, Najah; van Zandwijk, Nico; Reid, Glen

2017-11-17

MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR. The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.

[miR-143 inhibits cell proliferation through targeted regulating the expression of K-ras gene in HeLa cells].

PubMed

Qin, H X; Cui, H K; Pan, Y; Hu, R L; Zhu, L H; Wang, S J

2016-12-23

Objective: To explore the effect of microRNA miR-143 on the proliferation of cervical cancer HeLa cells through targeted regulating the expression of K-ras gene. Methods: The luciferase report carrier containing wild type 3'-UTR of K-ras gene (K-ras-wt) or mutated 3'-UTR of the K-ras (K-ras-mut) were co-transfected with iR-143 mimic into the HeLa cells respectively, and the targeting effect of miR-143 in the transfectants was verified by the dual luciferase report system. HeLa cells were also transfected with miR-143 mimic (miR-143 mimic group), mimic control (negative control group), and miR-143 mimic plus K-ras gene (miR-143 mimic+ K-ras group), respectively. The expression of miR-143 in the transfected HeLa cells was detected by real-time PCR (RT-PCR), and the expression of K-ras protein was detected by Western blot. The cell proliferation activity of each group was examined by MTT assay. In addition, human cervical cancer tissue samples ( n =5) and cervical intraepithelial neoplasia tissue samples ( n =5) were also examined for the expression of miR-143 and K-ras protein by RT-PCR and Western blot, respectively. Results: The luciferase report assay showed that co-transfection with miR-143 mimic decreased the luciferase activity of the K-ras-wt significantly, but did not inhibit the luciferase activity of the K-ras-mut. The expression of miR-143 in the HeLa cells transfected with miR-143 mimic was significantly higher than that in the HeLa cells transfected with the mimic control (3.31±0.45 vs 0.97±0.22, P <0.05). The MTT assay revealed that the cell proliferative activity of the miR-143 mimic group was significantly lower than that of the negative control group ( P <0.05), and the cell proliferative activity of the miR-143 mimic+ K-ras group was also significantly lower than the control group ( P <0.05) but higher than the miR-143 mimic group significantly ( P <0.05). The expression levels of K-ras protein in the miR-143 mimic group, the negative control group and the miR-143 mimic+ K-ras group were lowest, moderate, and highest, respectively (115.27±34.08, 521.36±41.89, and 706.52±89.44, all P <0.05). In the tissue samples, the miR-143 expression in the cervical cancer group was significantly lower than that of the cervical intraepithelial neoplasia group (0.32±0.06 vs. 0.93±0.17, P <0.05); whereas the K-ras protein expression in the cervical cancer group was significantly higher than that in the cervical intraepithelial neoplasia group (584.39±72.34 vs. 114.23±25.82, P <0.05). Conclusions: In vitro, miR-143 can inhibit the proliferative activity of HeLa cells through targeted regulating the expression of K-ras gene. In human cervical cancer tissues of a small sample set, the expression of miR-143 is downregulated, and the expression of K-ras is upregulated.

[Discussion of the implementation of MIMIC database in emergency medical study].

PubMed

Li, Kaiyuan; Feng, Cong; Jia, Lijing; Chen, Li; Pan, Fei; Li, Tanshi

2018-05-01

To introduce Medical Information Mart for Intensive Care (MIMIC) database and elaborate the approach of critically emergent research with big data based on the feature of MIMIC and updated studies both domestic and overseas, we put forward the feasibility and necessity of introducing medical big data to research in emergency. Then we discuss the role of MIMIC database in emergency clinical study, as well as the principles and key notes of experimental design and implementation under the medical big data circumstance. The implementation of MIMIC database in emergency medical research provides a brand new field for the early diagnosis, risk warning and prognosis of critical illness, however there are also limitations. To meet the era of big data, emergency medical database which is in accordance with our national condition is needed, which will provide new energy to the development of emergency medicine.

Polyvinylpyrrolidone (PVP)-Capped Pt Nanocubes with Superior Peroxidase-Like Activity

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

Ye, Haihang; Liu, Yuzi; Chhabra, Ashima

2016-12-21

Peroxidase mimics of inorganic nanoparticles are expected to circumvent the inherent issues of natural peroxidases, providing enhanced performance in important applications such as diagnosis and imaging. Despite the report of a variety of peroxidase mimics in the past decade, very limited progress has been made on improving their catalytic efficiency. The catalytic efficiencies of most previously reported mimics are only up to one order of magnitude higher than those of natural peroxidases. In this work, we demonstrate a type of highly efficient peroxidase mimic – polyvinylpyrrolidone (PVP)-capped Pt nanocubes of sub-10 nm in size. These PVP-capped Pt cubes are ~200-foldmore » more active than the natural counterparts and exhibit a record-high specific catalytic efficiency. In addition to the superior efficiency, the new mimic shows several other promising features, including excellent stabilities, well-controlled uniformity in both size and shape, controllable sizes, and facile and scalable production.« less

Complicated Genitourinary Tract Infections and Mimics.

PubMed

Yu, Michael; Robinson, Kathryn; Siegel, Cary; Menias, Christine

This article provides pictorial review of complicated upper and lower genitourinary infections and their mimics. Imaging features of upper urinary tract infections including uncomplicated acute pyelonephritis, xanthogranulomatous pyelonephritis (XGPN), emphysematous pyelonephritis, perirenal abscess, and pyonephrosis are first reviewed and then followed by pictorial review of their mimics including contrast-associated nephrotoxicity, renal infarcts, malakoplakia, renal cell cancer, leukemia or lymphoma and Castleman's disease. Next, imaging features of lower urinary tract infections including cystitis, emphysematous cystitis, enterovesical, colovesical and vesicovaginal fistulas, Fournier gangrene, prostatitis, epididymitis, and orchitis are reviewed and then followed by pictorial review of their mimics including gas in the bladder and perineum related to instrumentation, radiation cystitis, bladder cancer, testicular torsion, testicular trauma, and testicular cancer and lymphoma. Recognizing imaging characteristics of complicated genitourinary infections and their mimics would allow clinicians to provide appropriate timely management. Copyright © 2016 Elsevier Inc. All rights reserved.

Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

ERIC Educational Resources Information Center

Monty, Chelsea Nicole

2009-01-01

The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

Touch the Page and Mimic Me: Evaluation of a Talking-Pen Learning Tool

ERIC Educational Resources Information Center

Odakura, Abigail

2013-01-01

The purpose of this paper is to evaluate the talking-pen device called the Mimic Me, an educational technology product of a large English conversation school in Japan, as an educational learning tool. The product will be reviewed in terms of its developmental appropriateness for the target audience based on current research. Although the Mimic Me…

MRI-based finite element modeling of facial mimics: a case study on the paired zygomaticus major muscles.

PubMed

Fan, Ang-Xiao; Dakpé, Stéphanie; Dao, Tien Tuan; Pouletaut, Philippe; Rachik, Mohamed; Ho Ba Tho, Marie Christine

2017-07-01

Finite element simulation of facial mimics provides objective indicators about soft tissue functions for improving diagnosis, treatment and follow-up of facial disorders. There is a lack of in vivo experimental data for model development and validation. In this study, the contribution of the paired Zygomaticus Major (ZM) muscle contraction on the facial mimics was investigated using in vivo experimental data derived from MRI. Maximal relative differences of 7.7% and 37% were noted between MRI-based measurements and numerical outcomes for ZM and skin deformation behaviors respectively. This study opens a new direction to simulate facial mimics with in vivo data.

Vasculitis mimics.

PubMed

Molloy, Eamonn S; Langford, Carol A

2008-01-01

There are many disorders that may closely resemble the clinical, radiologic and/or pathologic features of the primary vasculitides. In this review, we focus on recently described and under-recognized syndromes that may mimic vasculitis. Hereditary causes of large-artery aneurysms such as Marfan's syndrome have long been recognized; recent years have seen a greater understanding of the genetics of Marfan's and other such disorders, including Loeys-Dietz syndrome and Ehler-Danlos syndrome type IV. Under-recognized mimics of medium-vessel vasculitis include segmental arterial mediolysis and Grange syndrome. A large number of entities can mimic small-vessel vasculitis. Recent descriptions of antibodies to human neutrophil elastase have provided insight into the occurrence of antineutrophil cytoplasmic antibodies in cocaine-induced midline destructive lesions. The differential diagnosis of cerebral vasculitis can be particularly difficult. Reversible cerebral vasoconstriction syndromes represent an important class of entities that can readily mimic cerebral vasculitis but have a very different management approach and outcome. The diagnosis of vasculitis requires careful assessment of all available clinical, laboratory, radiologic and pathologic information, and consideration of many competing differential diagnoses. Awareness of noninflammatory mimics of vasculitis is essential to avoid unnecessary and potentially harmful treatment with immunosuppressive agents.

Standardisation of the Japanese diet for use in animal experiments.

PubMed

Sugawara, Saeko; Mizowaki, Yui; Iwagaki, Yui; Sakamoto, Yu; Yamamoto, Kazushi; Tsuduki, Tsuyoshi

2017-11-01

The aim of this study was to develop a purified diet that mimics the characteristics of the Japanese diet using readily available materials with a simpler composition and a focus on quality, with the goal of facilitating performance of studies on the Japanese diet worldwide. The utility of the new diet was examined as a mimic of the standard Japanese diet for use in animal experiments. We examined whether a key characteristic of the Japanese diet of being less likely to cause obesity could be reproduced. The mimic diet had a balance of protein, fat and carbohydrate based on the 1975 Japanese diet, which is the least likely to cause obesity, and materials chosen with reference to the National Health and Nutrition Survey (NHNS). To examine similarities of the mimic diet with the model 1975 Japanese diet, we created a menu of the 1975 diet based on the NHNS and prepared the freeze-dried and powdered diet. The mimic diet, the 1975 Japanese diet, a control AIN-93G diet and a Western diet were fed to mice for 4 weeks. As a result, the mimic diet and the 1975 diet resulted in less accumulation of visceral fat and liver fat. Mice given these two diets showed similar effects. This indicates that the mimic diet used in this study has characteristics of the 1975 Japanese diet and could be used as a standard Japanese diet in animal experiments.

Utility of a tumor-mimic model for the evaluation of the accuracy of HIFU treatments. results of in vitro experiments in the liver.

PubMed

N'Djin, William Apoutou; Melodelima, David; Parmentier, Hubert; Chesnais, Sabrina; Rivoire, Michel; Chapelon, Jean Yves

2008-12-01

Presented in this article is a tumor-mimic model that allows the evaluation, before clinical trials, of the targeting accuracy of a high intensity focused ultrasound (HIFU) device for the treatment of the liver. The tumor-mimic models are made by injecting a warm solution that polymerizes in hepatic tissue and forms a 1 cm discrete lesion that is detectable by ultrasound imaging and gross pathology. First, the acoustical characteristics of the tumor-mimics model were measured in order to determine if this model could be used as a target for the evaluation of the accuracy of HIFU treatments without modifying HIFU lesions in terms of size, shape and homogeneity. On average (n = 10), the attenuation was 0.39 +/- 0.05 dB.cm(-1) at 1 MHz, the ultrasound propagation velocity was 1523 +/- 1 m.s(-1) and the acoustic impedance was 1.84 +/- 0.00 MRayls. Next, the tumor-mimic models were used in vitro in order to verify, at a preclinical stage, that lesions created by HIFU devices guided by ultrasound imaging are properly positioned in tissues. The HIFU device used in this study is a 256-element phased-array toroid transducer working at a frequency of 3 MHz with an integrated ultrasound imaging probe working at a frequency of 7.5 MHz. An initial series of in vitro experiments has shown that there is no significant difference in the dimensions of the HIFU lesions created in the liver with or without tumor-mimic models (p = 0.3049 and p = 0.8796 for the diameter and depth, respectively). A second in vitro study showed that HIFU treatments performed on five tumor-mimics with safety margins of at least 1 mm were properly positioned. The margins obtained were on average 9.3 +/- 2.7 mm (min. 3.0 - max. 20.0 mm). This article presents in vitro evidence that these tumor-mimics are identifiable by ultrasound imaging, they do not modify the geometry of HIFU lesions and, thus, they constitute a viable model of tumor-mimics indicated for HIFU therapy.

Millimeter-wave monolithic integrated circuit characterization by a picosecond optoelectronic technique

NASA Astrophysics Data System (ADS)

Hung, Hing-Loi A.; Smith, Thane; Huang, Ho C.; Polak-Dingels, Penny; Webb, Kevin J.

1989-08-01

The characterization of microwave and millimeter-wave monolithic integrated circits (MIMICs) using picosecond pulse-sampling techniques is developed with emphasis on improving broadband coverage and measurement accuracy. GaAs photoconductive swithces are used for signal generation and sampling operations. The measured time-domain response allows the spectral transfer function of the MIMIC to be obtained. This measurement technique is verified by characterization of the frequency response (magnitude and phase) of a reference 50-ohm microstrip line and a two-stage Ka-band MIMIC amplifier. The measured broadband results agree with those obtained from conventional frequency-domain measurements using a network analyzer. The application of this optical technique to on-wafer MIMIC characterization is described.

The golden mimicry complex uses a wide spectrum of defence to deter a community of predators

PubMed Central

Pekár, Stano; Petráková, Lenka; Bulbert, Matthew W; Whiting, Martin J; Herberstein, Marie E

2017-01-01

Mimicry complexes typically consist of multiple species that deter predators using similar anti-predatory signals. Mimics in these complexes are assumed to vary in their level of defence from highly defended through to moderately defended, or not defended at all. Here, we report a new multi-order mimicry complex that includes at least 140 different putative mimics from four arthropod orders including ants, wasps, bugs, tree hoppers and spiders. All members of this mimicry complex are characterised by a conspicuous golden body and an ant Gestalt, but vary substantially in their defensive traits. However, they were similarly effective at deterring predators - even mildly defended mimics were rarely eaten by a community of invertebrate and vertebrate predators both in the wild and during staged trials. We propose that despite the predominance of less defended mimics the three predatory guilds avoid the mimics because of the additive influence of the various defensive traits. DOI: http://dx.doi.org/10.7554/eLife.22089.001 PMID:28170317

MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes

PubMed Central

Venken, Koen J. T.; Schulze, Karen L.; Haelterman, Nele A.; Pan, Hongling; He, Yuchun; Evans-Holm, Martha; Carlson, Joseph W.; Levis, Robert W.; Spradling, Allan C.; Hoskins, Roger A.; Bellen, Hugo J.

2011-01-01

We demonstrate the versatility of a collection of insertions of the transposon Minos mediated integration cassette (MiMIC), in Drosophila melanogaster. MiMIC contains a gene-trap cassette and the yellow+ marker flanked by two inverted bacteriophage ΦC31 attP sites. MiMIC integrates almost at random in the genome to create sites for DNA manipulation. The attP sites allow the replacement of the intervening sequence of the transposon with any other sequence through recombinase mediated cassette exchange (RMCE). We can revert insertions that function as gene traps and cause mutant phenotypes to wild type by RMCE and modify insertions to control GAL4 or QF overexpression systems or perform lineage analysis using the Flp system. Insertions within coding introns can be exchanged with protein-tag cassettes to create fusion proteins to follow protein expression and perform biochemical experiments. The applications of MiMIC vastly extend the Drosophila melanogaster toolkit. PMID:21985007

Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

PubMed

Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

2016-06-01

In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MOCVD process technology for affordable, high-yield, high-performance MESFET structures. Phase 3: MIMIC

NASA Astrophysics Data System (ADS)

1993-01-01

Under the MIMIC Program, Spire has pursued improvements in the manufacturing of low cost, high quality gallium arsenide MOCVD wafers for advanced MIMIC FET applications. As a demonstration of such improvements, Spire was tasked to supply MOCVD wafers for comparison to MBE wafers in the fabrication of millimeter and microwave integrated circuits. In this, the final technical report for Spire's two-year MIMIC contract, we report the results of our work. The main objectives of Spire's MIMIC Phase 3 Program, as outlined in the Statement of Work, were as follows: Optimize the MOCVD growth conditions for the best possible electrical and morphological gallium arsenide. Optimization should include substrate and source qualification as well as determination of the optimum reactor growth conditions; Perform all work on 75 millimeter diameter wafers, using a reactor capable of at least three wafers per run; and Evaluate epitaxial layers using electrical, optical, and morphological tests to obtain thickness, carrier concentration, and mobility data across wafers.

IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage.

PubMed

Lin, Chiou-Feng; Chien, Shun-Yi; Chen, Chia-Ling; Hsieh, Chia-Yuan; Tseng, Po-Chun; Wang, Yu-Chih

2016-02-01

Treatment of interferon-γ (IFN-γ) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-γ signaling, this study investigated the link between autophagy and IFN-γ cytotoxicity. In A549 human lung cancer cells, IFN-γ treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6. Furthermore, IFN-γ signaling controlled mimic ETosis through a mechanism involving an autophagy- and Fas-associated protein with death domain-controlled caspase-8/-3 activation. Following caspase-mediated lamin degradation, IFN-γ caused DNA damage-associated ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM)-regulated mimic ETosis. Upon ATR/ATM signaling, peptidyl arginine deiminase 4 (PAD4)-mediated histone 3 citrullination promoted mimic ETosis. Such IFN-γ-induced effects were defective in PC14PE6/AS2 human lung cancer cells, which were unsusceptible to IFN-γ-induced autophagy. Due to autophagy-based caspase cascade activation, IFN-γ triggers unconventional caspase-mediated DNA damage, followed by ATR/ATM-regulated PAD4-mediated histone citrullination during mimic ETosis in lung epithelial malignancy.

Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets

PubMed Central

Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

2015-01-01

Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify d-peptide inhibitors of ebolavirus entry. PMID:25287718

The role of ultraviolet colour in the assessment of mimetic accuracy between Batesian mimics and their models: a case study using ant-mimicking spiders

NASA Astrophysics Data System (ADS)

Corcobado, Guadalupe; Herberstein, Marie E.; Pekár, Stano

2016-12-01

The use of ultraviolet (UV) cues for intra- and inter-specific communication is common in many animal species. Still, the role of UV signals under some predator-prey contexts, such as Batesian mimicry, is not clear. Batesian mimicry is a defensive strategy by which a palatable species (the mimic) resembles an unpalatable or noxious species (the model) to avoid predation. This strategy has evolved independently in many different taxa that are predated by species capable of UV perception. Moreover, there is considerable variation in how accurately Batesian mimics resemble their models across species. Our aim was to investigate how UV colour contributed to mimetic accuracy using several ant-mimicking spider species as a case study. We measured the reflectance spectrum (300-700 nm) for several species of mimics and models, and we tested whether they differ in visible and UV colour. We modelled whether two different predators could discriminate between mimics and models using colour information. We found that generally, ant-mimicking spiders differed significantly from their ant models in UV colour and that information from the visible range of light cannot be extrapolated into the UV. Our modelling suggested that wasps should be able to discriminate between mimics and models combining information from visible and the UV light, whereas birds may not discriminate between them. Thus, we show that UV colour can influence mimic accuracy and we discuss its potential role in Batesian mimicry. We conclude that colour, especially in the UV range, should be taken into account when measuring mimetic accuracy.

Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets.

PubMed

Clinton, Tracy R; Weinstock, Matthew T; Jacobsen, Michael T; Szabo-Fresnais, Nicolas; Pandya, Maya J; Whitby, Frank G; Herbert, Andrew S; Prugar, Laura I; McKinnon, Rena; Hill, Christopher P; Welch, Brett D; Dye, John M; Eckert, Debra M; Kay, Michael S

2015-04-01

Ebolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti-ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N-trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad-spectrum inhibitors of ebolavirus entry. The N-trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N-trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X-ray crystallography analyses reveal the helical, trimeric structure of the designed N-trimer mimic targets. Surface plasmon resonance studies validate that the N-trimer mimic binds its native ligand, the C-peptide region of GP2. The longest N-trimer mimic also inhibits virus entry, thereby confirming binding of the C-peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N-trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N-trimer mimics as targets in mirror-image phage display, which will be used to identify D-peptide inhibitors of ebolavirus entry. © 2014 The Protein Society.

A Backscattering Enhanced Microwave Canopy Scattering Model Based On MIMICS

NASA Astrophysics Data System (ADS)

Shen, X.; Hong, Y.; Qin, Q.; Chen, S.; Grout, T.

2010-12-01

For modeling microwave scattering of vegetated areas, several microwave canopy scattering models, based on the vectorized radiative transfer equation (VRT) that use different solving techniques, have been proposed in the past three decades. As an iterative solution of VRT at low orders, the Michigan Microwave Canopy Scattering Model (MIMICS) gives an analytical expression for calculating scattering as long as the volume scattering is not too strong. The most important usage of such models is to predict scattering in the backscattering direction. Unfortunately, the simplified assumption of MIMICS is that the scattering between the ground and trunk layers only includes the specular reflection. As a result, MIMICS includes a dominant coherent term which vanishes in the backscattering direction because this term contains a delta function factor of zero in this direction. This assumption needs reconsideration for accurately calculating the backscattering. In the framework of MIMICS, any incoherent terms that involve surface scattering factors must at least undergo surface scattering twice and volume scattering once. Therefore, these incoherent terms are usually very weak. On the other hand, due to the phenomenon of backscattering enhancement, the surface scattering in the backscattering direction is very strong compared to most other directions. Considering the facts discussed above, it is reasonable to add a surface backscattering term to the last equation of the boundary conditions of MIMICS. More terms appear in the final result including a backscattering coherent term which enhances the backscattering. The modified model is compared with the original MIMICS (version 1.0) using JPL/AIRSAR data from NASA Campaign Soil Moisture Experimental 2003 (SMEX03) and Washita92. Significant improvement is observed.

Synthesis and Functional Characterization of Novel Sialyl LewisX Mimic-Decorated Liposomes for E-selectin-Mediated Targeting to Inflamed Endothelial Cells.

PubMed

Chantarasrivong, Chanikarn; Ueki, Akiharu; Ohyama, Ryutaro; Unga, Johan; Nakamura, Shinya; Nakanishi, Isao; Higuchi, Yuriko; Kawakami, Shigeru; Ando, Hiromune; Imamura, Akihiro; Ishida, Hideharu; Yamashita, Fumiyoshi; Kiso, Makoto; Hashida, Mitsuru

2017-05-01

Sialyl LewisX (sLeX) is a natural ligand of E-selectin that is overexpressed by inflamed and tumor endothelium. Although sLeX is a potential ligand for drug targeting, synthesis of the tetrasaccharide is complicated with many reaction steps. In this study, structurally simplified novel sLeX analogues were designed and linked with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG) for E-selectin-mediated liposomal delivery. The sLeX structural simplification strategies include (1) replacement of the Gal-GlcNAc disaccharide unit with lactose to reduce many initial steps and (2) substitution of neuraminic acid with a negatively charged group, i.e., 3'-sulfo, 3'-carboxymethyl (3'-CM), or 3'-(1-carboxy)ethyl (3'-CE). While all the liposomes developed were similar in particle size and charge, the 3'-CE sLeX mimic liposome demonstrated the highest uptake in inflammatory cytokine-treated human umbilical vein endothelial cells (HUVECs), being even more potent than native sLeX-decorated liposomes. Inhibition studies using antiselectin antibodies revealed that their uptake was mediated primarily by overexpressed E-selectin on inflamed HUVECs. Molecular dynamics simulations were performed to gain mechanistic insight into the E-selectin binding differences among native and mimic sLeX. The terminally branched methyl group of the 3'-CE sLeX mimic oriented and faced the bulk hydrophilic solution during E-selectin binding. Since this state is entropically unfavorable, the 3'-CE sLeX mimic molecule might be pushed toward the binding pocket of E-selectin by a hydrophobic effect, leading to a higher probability of hydrogen-bond formation than native sLeX and the 3'-CM sLeX mimic. This corresponded with the fact that the 3'-CE sLeX mimic liposome exhibited much greater uptake than the 3'-CM sLeX mimic liposome.

Peroxidase-like activity of the Co3O4 nanoparticles used for biodetection and evaluation of antioxidant behavior

NASA Astrophysics Data System (ADS)

Jia, Huimin; Yang, Dongfang; Han, Xiangna; Cai, Junhui; Liu, Haiying; He, Weiwei

2016-03-01

Nanostructured enzyme mimics are of great interest as promising alternatives to artificial enzymes for biomedical and catalytic applications. Studying the chemical interactions between antioxidants and nano-enzymes may result in a better understanding of the antioxidant capability of antioxidants and may help improve the function of artificial enzymes to better mimic natural enzymes. In this study, using Co3O4 nanoparticles (NPs) as peroxidase mimics to catalyze the oxidation of chromophoric substrates by H2O2, we developed a platform that acts as a biosensor for hydrogen peroxide and glucose and that can study the inhibitory effects of natural antioxidants on peroxidase mimics. This method can be applied specifically to glucose detection in real samples. Three natural antioxidants, gallic acid (GA), tannic acid (TA), and ascorbic acid (AA), were compared for their antioxidant capabilities. We found that these three antioxidants efficiently inhibit peroxidase-like activity with concentration dependence. The antioxidants showed different efficiencies, in the following order: tannic acid > gallic acid > ascorbic acid. They also showed distinct modes of inhibition based on different interaction mechanisms. This study serves as a proof-of-concept that nano-enzyme mimics can be used to evaluate antioxidant capabilities and to screen enzyme inhibitors.Nanostructured enzyme mimics are of great interest as promising alternatives to artificial enzymes for biomedical and catalytic applications. Studying the chemical interactions between antioxidants and nano-enzymes may result in a better understanding of the antioxidant capability of antioxidants and may help improve the function of artificial enzymes to better mimic natural enzymes. In this study, using Co3O4 nanoparticles (NPs) as peroxidase mimics to catalyze the oxidation of chromophoric substrates by H2O2, we developed a platform that acts as a biosensor for hydrogen peroxide and glucose and that can study the inhibitory effects of natural antioxidants on peroxidase mimics. This method can be applied specifically to glucose detection in real samples. Three natural antioxidants, gallic acid (GA), tannic acid (TA), and ascorbic acid (AA), were compared for their antioxidant capabilities. We found that these three antioxidants efficiently inhibit peroxidase-like activity with concentration dependence. The antioxidants showed different efficiencies, in the following order: tannic acid > gallic acid > ascorbic acid. They also showed distinct modes of inhibition based on different interaction mechanisms. This study serves as a proof-of-concept that nano-enzyme mimics can be used to evaluate antioxidant capabilities and to screen enzyme inhibitors. Electronic supplementary information (ESI) available: Fig. S1-S6. See DOI: 10.1039/c6nr00860g

Reexpression of Prior Stroke Symptoms in Adults: When is a Mimic a Mimic?

PubMed

Siegler, James E; George, Alexander J; Martin-Schild, Sheryl

2017-09-01

A "stroke mimic" refers to any clinical condition that causes neurological symptoms clinically indistinguishable from a cerebral lesion that affects a vascular distribution, but is not caused by ischemia. One subtype of stroke mimic, termed stroke reexpression, is a form of mimicry in which previously recovered or improved stroke symptoms recur in the setting of a neurological disturbance (seizure, hypoperfusion state) or a systemic disturbance (toxic, metabolic, infectious). Many reports of stroke reexpression exist in the literature and are well known to clinicians, but there has been no consensus regarding terminology that has been published to date. The purpose of this review is to summarize several examples of stroke reexpression and propose simple, useful criteria for this clinical condition.

Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm.

PubMed

Albuquerque, Maria T P; Ryan, Stuart J; Münchow, Eliseu A; Kamocka, Maria M; Gregory, Richard L; Valera, Marcia C; Bottino, Marco C

2015-08-01

Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)-mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm(3), n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P < .05) reduction in the percentage of viable bacteria compared with the negative control and PDS. Our findings suggest that TAP-mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Implication of left ventricular diastolic dysfunction in cryptogenic ischemic stroke.

PubMed

Seo, Jae-Young; Lee, Kyung Bok; Lee, Jung-Gon; Kim, Ji-Sun; Roh, Hakjae; Ahn, Moo-Young; Park, Byoung Won; Hyon, Min Su

2014-09-01

Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non-cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non-cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99-6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42-9.17) were independently related to stroke with AF after adjusting covariates. The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non-cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS. © 2014 American Heart Association, Inc.

Formation of a stable mimic of ambient particulate matter containing viable infectious respiratory syncytial virus and its dry-deposition directly onto cell cultures.

PubMed

Cruz-Sanchez, Teresita M; Haddrell, Allen E; Hackett, Tillie L; Singhera, Gurpreet K; Marchant, David; Lekivetz, Ryan; Meredith, Anna; Horne, Derrick; Knight, Darryl A; van Eeden, Stephen F; Bai, Tony R; Hegele, Richard G; Dorscheid, Delbert R; Agnes, George R

2013-01-15

Epidemiological associations of worse respiratory outcomes from combined exposure to ambient particulate matter (PM) and respiratory viral infection suggest possible interactions between PM and viruses. To characterize outcomes of such exposures, we developed an in vitro mimic of the in vivo event of exposure to PM contaminated with respiratory syncytial virus (RSV). Concentration of infectious RSV stocks and a particle levitation apparatus were the foundations of the methodology developed to generate specific numbers of PM mimics (PM(Mimics)) of known composition for dry, direct deposition onto airway epithelial cell cultures. Three types of PM(Mimics) were generated for this study: (i) carbon alone (P(C)), (ii) carbon and infectious RSV (P(C+RSV)), and (iii) aerosols consisting of RSV (A(RSV)). P(C+RSV) were stable in solution and harbored infectious RSV for up to 6 months. Unlike A(RSV) infection, P(C+RSV) infection was found to be dynamin dependent and to cause lysosomal rupture. Cells dosed with PM(Mimics) comprised of RSV (A(RSV)), carbon (P(C)), or RSV and carbon (P(C+RSV)) responded differentially as exemplified by the secretion patterns of IL-6 and IL-8. Upon infection, and prior to lung cell death due to viral infection, regression analysis of these two mediators in response to incubation with A(RSV), P(C), or P(C+RSV) yielded higher concentrations upon infection with the latter and at earlier time points than the other PM(Mimics). In conclusion, this experimental platform provides an approach to study the combined effects of PM-viral interactions and airway epithelial exposures in the pathogenesis of respiratory diseases involving inhalation of environmental agents.

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

PubMed Central

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

2016-01-01

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

PubMed

Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

2016-08-26

High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic.

PubMed

Li, Bao-qiu; Dong, Xin; Li, Na; Gao, Ji-you; Yuan, Qiang; Fang, Shi-hong; Gong, Xian-chang; Wang, Shu-juan; Wang, Feng-shan

2014-10-01

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10 µmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 µmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic. © 2014 by the Society for Experimental Biology and Medicine.

The evolution of a Müllerian mimic in a spatially distributed community.

PubMed

Joron, Mathieu; Iwasa, Yoh

2005-11-07

Strong positive density-dependence should lead to a loss of diversity, but warning-colour and Müllerian mimicry systems show extraordinary levels of diversity. Here, we propose an analytical model to explore the dynamics of two forms of a Müllerian mimic in a heterogeneous environment with two alternative model species. Two connected populations of a dimorphic, chemically defended mimic are allowed to evolve and disperse. The proportions of the respective model species vary spatially. We use a nonlinear approximation of Müller's number-dependent equations to model a situation where the mortality for either form of the mimic decreases hyberbolically when its local density increases. A first non-spatial analysis confirms that the positive density-dependence makes coexistence of mimetic forms unstable in a single isolated patch, but shows that mimicry of the rarer model can be stable once established. The two-patch analysis shows that when models have different abundance in different places, local mimetic diversity in the mimic is maintained only if spatial heterogeneity is strong, or, more interestingly, if the mimic is not too strongly distasteful. Therefore, mildly toxic species can become polymorphic in a wider range of ecological settings. Spatial dynamics thus reveal a region of Müllerian polymorphism separating classical Batesian polymorphism and Müllerian monomorphism along the mimic's palatability spectrum. Such polymorphism-palatability relationship in a spatial environment provides a parsimonious hypothesis accounting for the observed Müllerian polymorphism that does not require quasi-Batesian dynamics. While the stability of coexistence depends on all factors, only the migration rate and strength of selection appear to affect the level of diversity at the polymorphic equilibrium. Local adaptation is predicted in most polymorphic cases. These results are in very good accordance with recent empirical findings on the polymorphic butterflies Heliconius numata and H. cydno.

Target research on tumor biology characteristics of mir-155-5p regulation on gastric cancer cell.

PubMed

Feng, Jun-an

2016-03-01

After the mir-155-5p over expressed in gastric cancer cells, the expression profile chip was adopted to screen its target genes. Some of the intersection of target genes were selected based on the bioinformatics prediction, in order to study the mechanism of its function and role of research. Affymetrix eukaryotic gene expression spectrum was conducted to screen mir-155-5p regulated genetic experiment. Western blot technique was employed to detect and screen the protein expression of target genes. Mimics was transfected in BGC-823 of gastric cancer cells. Compared with mimics-nc group and mock group, the mRNA expression quantities of SMAD1, STAT1, CAB39, CXCR4 and CA9 were significantly lower. After the gastric cancer cells BGC-823 and MKN-45 had been transfected by mimics, compared with mimics-nc (MNC) group and mock (MOCK) group, it was decreased for the protein expression of SMAD1, STAT1 and CAB39 in mimics (MIMICS) group. The verification of qRT-PCR demonstrated that SMAD1, STAT1, CAB39, CXCR4 and CA9 were the predicted target genes and target proteins of mir-155-5p, the over expression of mir-155-5p could enable the decreasing of its expression level in gastric cancer cells MKN-45 and BGC-823.

Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD.

PubMed

He, Shuying; Guo, Weihong; Deng, Feihong; Chen, Kequan; Jiang, Yonghong; Dong, Minyu; Peng, Liang; Chen, Xueqing

2018-03-21

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b -/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.

Walking like an ant: a quantitative and experimental approach to understanding locomotor mimicry in the jumping spider Myrmarachne formicaria

PubMed Central

Hoy, Ron R.; Cohen, Itai; Beatus, Tsevi

2017-01-01

Protective mimicry, in which a palatable species avoids predation by being mistaken for an unpalatable model, is a remarkable example of adaptive evolution. These complex interactions between mimics, models and predators can explain similarities between organisms beyond the often-mechanistic constraints typically invoked in studies of convergent evolution. However, quantitative studies of protective mimicry typically focus on static traits (e.g. colour and shape) rather than on dynamic traits like locomotion. Here, we use high-speed cameras and behavioural experiments to investigate the role of locomotor behaviour in mimicry by the ant-mimicking jumping spider Myrmarachne formicaria, comparing its movement to that of ants and non-mimicking spiders. Contrary to previous suggestions, we find mimics walk using all eight legs, raising their forelegs like ant antennae only when stationary. Mimics exhibited winding trajectories (typical wavelength = 5–10 body lengths), which resemble the winding patterns of ants specifically engaged in pheromone-trail following, although mimics walked on chemically inert surfaces. Mimics also make characteristically short (approx. 100 ms) pauses. Our analysis suggests that this makes mimics appear ant-like to observers with slow visual systems. Finally, behavioural experiments with predatory spiders yield results consistent with the protective mimicry hypothesis. These findings highlight the importance of dynamic behaviours and observer perception in mimicry. PMID:28701553

High-fidelity in vivo replication of DNA base shape mimics without Watson–Crick hydrogen bonds

PubMed Central

Delaney, James C.; Henderson, Paul T.; Helquist, Sandra A.; Morales, Juan C.; Essigmann, John M.; Kool, Eric T.

2003-01-01

We report studies testing the importance of Watson–Crick hydrogen bonding, base-pair geometry, and steric effects during DNA replication in living bacterial cells. Nonpolar DNA base shape mimics of thymine and adenine (abbreviated F and Q, respectively) were introduced into Escherichia coli by insertion into a phage genome followed by transfection of the vector into bacteria. Genetic assays showed that these two base mimics were bypassed with moderate to high efficiency in the cells and with very high efficiency under damage-response (SOS induction) conditions. Under both sets of conditions, the T-shape mimic (F) encoded genetic information in the bacteria as if it were thymine, directing incorporation of adenine opposite it with high fidelity. Similarly, the A mimic (Q) directed incorporation of thymine opposite itself with high fidelity. The data establish that Watson–Crick hydrogen bonding is not necessary for high-fidelity replication of a base pair in vivo. The results suggest that recognition of DNA base shape alone serves as the most powerful determinant of fidelity during transfer of genetic information in a living organism. PMID:12676985

Retention of robot-assisted surgical skills in urological surgeons acquired using Mimic dV-Trainer.

PubMed

Teishima, Jun; Hattori, Minoru; Inoue, Shogo; Ikeda, Kenichiro; Hieda, Keisuke; Ohara, Shinya; Egi, Hiroyuki; Ohdan, Hideki; Matsubara, Akio

2014-07-01

We assess the retention of robot-assisted surgical skills among urologic surgeons. The robot-assisted surgery skills of 20 urologic surgeons were assessed using a Mimic dV-Trainer program (Mimic Technologies, Inc., Seattle, WA) consisting of 6 tasks. These 20 surgeons had no previous experience either using the Mimic dV-Trainer or acting as the main surgeon in robot-assisted surgery. The surgeons completed the program 4 times in a row; after 1 year, they completed it again for a fifth time. Performance scores were recorded using the Mimic dV-Trainer's built-in algorithm. For all 6 tasks, there were significant improvements to the scores in the fourth trials compared with those in the first trials. The scores in the fifth trials did not significantly decline compared with those in the fourth trials. There was no significant difference between the fifth trial scores of surgeons with laparoscopic surgery skills/experience and those without. Our results indicate that fundamental robot-assisted surgical skills can be retained in the long-term after they are acquired.

The encapsulation of cell-free transcription and translation machinery in vesicles for the construction of cellular mimics.

PubMed

Spencer, Amy C; Torre, Paola; Mansy, Sheref S

2013-10-21

As interest shifts from individual molecules to systems of molecules, an increasing number of laboratories have sought to build from the bottom up cellular mimics that better represent the complexity of cellular life. To date there are a number of paths that could be taken to build compartmentalized cellular mimics, including the exploitation of water-in-oil emulsions, microfluidic devices, and vesicles. Each of the available options has specific advantages and disadvantages. For example, water-in-oil emulsions give high encapsulation efficiency but do not mimic well the permeability barrier of living cells. The primary advantage of the methods described herein is that they are all easy and cheap to implement. Transcription-translation machinery is encapsulated inside of phospholipid vesicles through a process that exploits common instrumentation, such as a centrifugal evaporator and an extruder. Reactions are monitored by fluorescence spectroscopy. The protocols can be adapted for recombinant protein expression, the construction of cellular mimics, the exploration of the minimum requirements for cellular life, or the assembly of genetic circuitry.

System and method for a parallel immunoassay system

DOEpatents

Stevens, Fred J.

2002-01-01

A method and system for detecting a target antigen using massively parallel immunoassay technology. In this system, high affinity antibodies of the antigen are covalently linked to small beads or particles. The beads are exposed to a solution containing DNA-oligomer-mimics of the antigen. The mimics which are reactive with the covalently attached antibody or antibodies will bind to the appropriate antibody molecule on the bead. The particles or beads are then washed to remove any unbound DNA-oligomer-mimics and are then immobilized or trapped. The bead-antibody complexes are then exposed to a test solution which may contain the targeted antigens. If the antigen is present it will replace the mimic since it has a greater affinity for the respective antibody. The particles are then removed from the solution leaving a residual solution. This residual solution is applied a DNA chip containing many samples of complimentary DNA. If the DNA tag from a mimic binds with its complimentary DNA, it indicates the presence of the target antigen. A flourescent tag can be used to more easily identify the bound DNA tag.

The Encapsulation of Cell-free Transcription and Translation Machinery in Vesicles for the Construction of Cellular Mimics

PubMed Central

Spencer, Amy C.; Torre, Paola; Mansy, Sheref S.

2013-01-01

As interest shifts from individual molecules to systems of molecules, an increasing number of laboratories have sought to build from the bottom up cellular mimics that better represent the complexity of cellular life. To date there are a number of paths that could be taken to build compartmentalized cellular mimics, including the exploitation of water-in-oil emulsions, microfluidic devices, and vesicles. Each of the available options has specific advantages and disadvantages. For example, water-in-oil emulsions give high encapsulation efficiency but do not mimic well the permeability barrier of living cells. The primary advantage of the methods described herein is that they are all easy and cheap to implement. Transcription-translation machinery is encapsulated inside of phospholipid vesicles through a process that exploits common instrumentation, such as a centrifugal evaporator and an extruder. Reactions are monitored by fluorescence spectroscopy. The protocols can be adapted for recombinant protein expression, the construction of cellular mimics, the exploration of the minimum requirements for cellular life, or the assembly of genetic circuitry. PMID:24192867

Design, synthesis and biological evaluation of paclitaxel-mimics possessing only the oxetane D-ring and side chain structures.

PubMed

Chen, Xing-Xiu; Gao, Feng; Wang, Qi; Huang, Xing; Wang, Dan

2014-01-01

Two spiro paclitaxel-mimics consisting only of an oxetane D-ring and a C-13 side chain were designed and synthesized on the basis of analysis of structure-activity relationships (SAR) of paclitaxel. In vitro microtubule-stabilizing and antiproliferative assays indicated a moderate weaker activity of the mimics than paclitaxel, but which still represented the first example of simplified paclitaxel analogues with significant anti-tumor biological activity. Copyright © 2013 Elsevier B.V. All rights reserved.

New synthesis of a stereoisomeric mixture of methyl 12-trishomofarnesoate, a juvenile hormone mimic useful in sericulture by increasing silk production

PubMed Central

MORI, Kenji

2017-01-01

A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.). PMID:29021513

New synthesis of a stereoisomeric mixture of methyl 12-trishomofarnesoate, a juvenile hormone mimic useful in sericulture by increasing silk production.

PubMed

Mori, Kenji

2017-01-01

A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.).

Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug Sunitinib in Glioblastoma.

PubMed

Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Huo, Lei; Liu, Jinfang; Lu, Jingchen

2015-06-01

Although aggressive therapeutic regimen has been applied in the treatment of Glioblastoma (GBM), the prognosis of patients with GBM remains poor. Preclinical studies have demonstrated the efficacy of Suntinib in GBM both in vitro and in vivo. In this study, we showed that the cytotoxicity was enhanced by transfection with miR-145 mimic. In addition, we suggested that the enhanced cytotoxicity of Sunitinib by miR-145 mimic was mediated by inhibition of both P-gp and Bcrp.

Imaging Review of Skeletal Tumors of the Pelvis Malignant Tumors and Tumor Mimics

PubMed Central

Girish, Gandikota; Finlay, Karen; Fessell, David; Pai, Deepa; Dong, Qian; Jamadar, David

2012-01-01

Malignant lesions of the pelvis are not uncommon and need to be differentiated from benign lesions and tumor mimics. Appearances are sometimes nonspecific leading to consideration of a broad differential diagnosis. Clinical history, anatomic location, and imaging characterization can help narrow the differential diagnosis. The focus of this paper is to demonstrate the imaging features and the role of plain films, computed tomography, and magnetic resonance imaging for detecting and characterizing malignant osseous pelvic lesions and their common mimics. PMID:22593667

Traumatic aortic injury: CT findings, mimics, and therapeutic options

PubMed Central

Lantz, Eric J.; Johnson, C. Michael; Young, Philip M.

2014-01-01

Objective Traumatic aortic injury (TAI) is rare, but frequently lethal. However, with prompt diagnosis, patients can undergo life-saving open or endovascular repair. Unfortunately, because these injuries are relatively rare, subtle forms of these injuries may be missed, and normal variants may mimic TAI leading to misdiagnosis. Conclusions We will discuss computed tomography findings of typical injury patterns of traumatic aortic injuries as well as treatment options, diagnostic pitfalls and injury mimics. These are highlighted with clinical case examples. PMID:25009793

26 CFR 1.1092(d)-2 - Personal property.

Code of Federal Regulations, 2010 CFR

2010-04-01

... principal holdings mimic the performance of the stocks included in the stock index (or alternatively a portfolio of stocks whose performance mimics the performance of the stocks included in the stock index). [T...

Reproducing a Prospective Clinical Study as a Computational Retrospective Study in MIMIC-II.

PubMed

Kury, Fabrício S P; Huser, Vojtech; Cimino, James J

2015-01-01

In this paper we sought to reproduce, as a computational retrospective study in an EHR database (MIMIC-II), a recent large prospective clinical study: the 2013 publication, by the Japanese Association for Acute Medicine (JAAM), about disseminated intravascular coagulation, in the journal Critical Care (PMID: 23787004). We designed in SQL and Java a set of electronic phenotypes that reproduced the study's data sampling, and used R to perform the same statistical inference procedures. All produced source code is available online at https://github.com/fabkury/paamia2015. Our program identified 2,257 eligible patients in MIMIC-II, and the results remarkably agreed with the prospective study. A minority of the needed data elements was not found in MIMIC-II, and statistically significant inferences were possible in the majority of the cases.

Müllerian and Batesian mimicry out, Darwinian and Wallacian mimicry in, for rewarding/rewardless flowers.

PubMed

Lev-Yadun, Simcha

2018-06-11

Müllerian and Batesian mimicry were originally defined in defensive (anti-predetory) animal systems. Later these terms were adopted by botanists studying pollination that defined rewarding flowers as Müllerian mimics and rewardless flowers as Batesian mimics. The use of these terms concerning pollination predated our recent understanding of how common plant aposematism is and the related defensive Müllerian and Batesian mimicry types. Being non-defensive, using the terms Müllerian and Batesian mimicry for rewarding/rewardless flowers is, however, confusing if not misleading, and is also logically inappropriate. I suggest to first stop using the terms Batesian and Müllerian mimicry concerning rewarding/rewardless flowers and pollination, and second, to define the guild of flowers that reward pollinatiors as Darwinian mimics and those that do not reward pollinators as Wallacian mimics.

Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

PubMed Central

2013-01-01

Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

Enzyme-Triggered Defined Protein Nanoarrays: Efficient Light-Harvesting Systems to Mimic Chloroplasts.

PubMed

Zhao, Linlu; Zou, Haoyang; Zhang, Hao; Sun, Hongcheng; Wang, Tingting; Pan, Tiezheng; Li, Xiumei; Bai, Yushi; Qiao, Shanpeng; Luo, Quan; Xu, Jiayun; Hou, Chunxi; Liu, Junqiu

2017-01-24

The elegance and efficiency by which chloroplasts harvest solar energy and conduct energy transfer have been a source of inspiration for chemists to mimic such process. However, precise manipulation to obtain orderly arranged antenna chromophores in constructing artificial chloroplast mimics was a great challenge, especially from the structural similarity and bioaffinity standpoints. Here we reported a design strategy that combined covalent and noncovalent interactions to prepare a protein-based light-harvesting system to mimic chloroplasts. Cricoid stable protein one (SP1) was utilized as a building block model. Under enzyme-triggered covalent protein assembly, mutant SP1 with tyrosine (Tyr) residues at the designated sites can couple together to form nanostructures. Through controlling the Tyr sites on the protein surface, we can manipulate the assembly orientation to respectively generate 1D nanotubes and 2D nanosheets. The excellent stability endowed the self-assembled protein architectures with promising applications. We further integrated quantum dots (QDs) possessing optical and electronic properties with the 2D nanosheets to fabricate chloroplast mimics. By attaching different sized QDs as donor and acceptor chromophores to the negatively charged surface of SP1-based protein nanosheets via electrostatic interactions, we successfully developed an artificial light-harvesting system. The assembled protein nanosheets structurally resembled the natural thylakoids, and the QDs can achieve pronounced FRET phenomenon just like the chlorophylls. Therefore, the coassembled system was meaningful to explore the photosynthetic process in vitro, as it was designed to mimic the natural chloroplast.

Context-dependent discrimination and the evolution of mimicry.

PubMed

Holen, Øistein Haugsten; Johnstone, Rufus A

2006-03-01

Many mimetic organisms have evolved a close resemblance to their models, making it difficult to discriminate between them on the basis of appearance alone. However, if mimics and models differ slightly in their activity patterns, behavior, or use of microhabitats, the exact circumstances under which a signaler is encountered may provide additional clues to its identity. We employ an optimality model of mimetic discrimination in which signal receivers obtain information about the relative risk of encountering mimics and models by observing an external background cue and flexibly adjust their response thresholds. Although such flexibility on the part of signal receivers has been predicted by theory and is supported by empirical evidence in a range of biological settings, little is known about the effects it has on signalers. We show that the presence of external cues that partly reveal signaler identity may benefit models and harm mimics, harm both, or even benefit both, depending on ecological circumstances. Moreover, if mimetic traits are costly to express, or mimics are related to their neighbors, context-dependent discrimination can dramatically alter the outcome of mimetic evolution. We discuss context-dependent discrimination among signal receivers in relation to small-scale synchrony in model and mimic activity patterns.

Behavioural mimicry in flight path of Batesian intraspecific polymorphic butterfly Papilio polytes

PubMed Central

Kitamura, Tasuku; Imafuku, Michio

2015-01-01

Batesian mimics that show similar coloration to unpalatable models gain a fitness advantage of reduced predation. Beyond physical similarity, mimics often exhibit behaviour similar to their models, further enhancing their protection against predation by mimicking not only the model's physical appearance but also activity. In butterflies, there is a strong correlation between palatability and flight velocity, but there is only weak correlation between palatability and flight path. Little is known about how Batesian mimics fly. Here, we explored the flight behaviour of four butterfly species/morphs: unpalatable model Pachliopta aristolochiae, mimetic and non-mimetic females of female-limited mimic Papilio polytes, and palatable control Papilio xuthus. We demonstrated that the directional change (DC) generated by wingbeats and the standard deviation of directional change (SDDC) of mimetic females and their models were smaller than those of non-mimetic females and palatable controls. Furthermore, we found no significant difference in flight velocity among all species/morphs. By showing that DC and SDDC of mimetic females resemble those of models, we provide the first evidence for the existence of behavioural mimicry in flight path by a Batesian mimic butterfly. PMID:26041360

Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.

PubMed

Daige, Christopher L; Wiggins, Jason F; Priddy, Leslie; Nelligan-Davis, Terri; Zhao, Jane; Brown, David

2014-10-01

miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. ©2014 American Association for Cancer Research.

Behavioural mimicry in flight path of Batesian intraspecific polymorphic butterfly Papilio polytes.

PubMed

Kitamura, Tasuku; Imafuku, Michio

2015-06-22

Batesian mimics that show similar coloration to unpalatable models gain a fitness advantage of reduced predation. Beyond physical similarity, mimics often exhibit behaviour similar to their models, further enhancing their protection against predation by mimicking not only the model's physical appearance but also activity. In butterflies, there is a strong correlation between palatability and flight velocity, but there is only weak correlation between palatability and flight path. Little is known about how Batesian mimics fly. Here, we explored the flight behaviour of four butterfly species/morphs: unpalatable model Pachliopta aristolochiae, mimetic and non-mimetic females of female-limited mimic Papilio polytes, and palatable control Papilio xuthus. We demonstrated that the directional change (DC) generated by wingbeats and the standard deviation of directional change (SDDC) of mimetic females and their models were smaller than those of non-mimetic females and palatable controls. Furthermore, we found no significant difference in flight velocity among all species/morphs. By showing that DC and SDDC of mimetic females resemble those of models, we provide the first evidence for the existence of behavioural mimicry in flight path by a Batesian mimic butterfly. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Effects of distance from models on the fitness of floral mimics.

PubMed

Duffy, K J; Johnson, S D

2017-05-01

Rewardless plants can attract pollinators by mimicking floral traits of rewarding heterospecific plants. This should result in the pollination success of floral mimics being dependent on the relative abundance of their models, as pollinator abundance and conditioning on model signals should be higher in the vicinity of the models. However, the attraction of pollinators to signals of the models may be partially innate, such that spatial isolation of mimics from model species may not strongly affect pollination success of mimics. We tested whether pollination rates and fruit set of the rewardless orchid Disa pulchra were influenced by proximity and abundance of its rewarding model species, Watsonia lepida. Pollination success of the orchid increased with proximity to the model species, while fruit set of the orchid increased with local abundance of the model species. Orchids that were experimentally translocated outside the model population experienced reduced pollinaria removal and increased pollinator-mediated self-pollination. These results confirm predictions that the pollination success of floral mimics should be dependent on the proximity and abundance of model taxa, and thus highlight the importance of ecological facilitation among species involved in mimicry systems. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

Microwave and millimeter wave monolithic integrated circuits (MIMIC) program. MIMIC briefs: Summaries of phase 3 technology support programs

NASA Astrophysics Data System (ADS)

Kramer, Warner

1993-01-01

This publication contains technical and contractual summaries of the MIMIC program's Phase 3 technology support programs. Each project description includes a discussion of the objectives of the effort, the approach pursued, and recent progress. Also identified are the performing organization(s), principal investigator and/or other key personnel, contract number, program funding and duration, and program monitor/COTR. Concluding the document is a directory of the personnel associated with these projects, from whom more information may be requested.

CSF tapping also improves mental imagery of gait in normal pressure hydrocephalus.

PubMed

Marques, Bruno; Laidet, Magali; Armand, Stéphane; Assal, Frédéric; Allali, Gilles

2017-11-01

This study aims to compare the changes of Timed Up and Go (TUG) and its imagined version (iTUG) after CSF tapping between patients with idiopathic normal pressure hydrocephalus (iNPH) and its mimics. TUG and iTUG were performed before and 24 h after CSF tapping in 117 patients (75.8 ± 6.9 years; 35% female) with suspicion of iNPH (68 iNPH and 49 mimics). Mental imagery of locomotion was modified after CSF tapping in iNPH patients, but not in the mimics.

I. The design, synthesis, and structure of antiparallel beta-sheet and beta-strand mimics. II. The design of a scripted chemistry outreach program to high schools

NASA Astrophysics Data System (ADS)

Waldman, Amy Sue

I. Protein structure is not easily predicted from the linear sequence of amino acids. An increased ability to create protein structures would allow researchers to develop new peptide-based therapeutics and materials, and would provide insights into the mechanisms of protein folding. Toward this end, we have designed and synthesized two-stranded antiparallel beta-sheet mimics containing conformationally biased scaffolds and semicarbazide, urea, and hydrazide linker groups that attach peptide chains to the scaffold. The mimics exhibited populations of intramolecularly hydrogen-bonded beta-sheet-like conformers as determined by spectroscopic techniques such as FTIR, sp1H NMR, and ROESY studies. During our studies, we determined that a urea-hydrazide beta-strand mimic was able to tightly hydrogen bond to peptides in an antiparallel beta-sheet-like configuration. Several derivatives of the urea-hydrazide beta-strand mimic were synthesized. Preliminary data by electron microscopy indicate that the beta-strand mimics have an effect on the folding of Alzheimer's Abeta peptide. These data suggest that the urea-hydrazide beta-strand mimics and related compounds may be developed into therapeutics which effect the folding of the Abeta peptide into neurotoxic aggregates. II. In recent years, there has been concern about the low level of science literacy and science interest among Americans. A declining interest in science impacts the abilities of people to make informed decisions about technology. To increase the interest in science among secondary students, we have developed the UCI Chemistry Outreach Program to High Schools. The Program features demonstration shows and discussions about chemistry in everyday life. The development and use of show scripts has enabled large numbers of graduate and undergraduate student volunteers to demonstrate chemistry to more than 12,000 local high school students. Teachers, students, and volunteers have expressed their enjoyment of The UCI Chemistry Outreach Program to High Schools.

Design and characterization of a tunable opto-mechatronic system to mimic the focusing and the regulation of illumination in the formation of images made by the human eye

NASA Astrophysics Data System (ADS)

Santiago-Alvarado, A.; Cruz-Félix, A.; Hernández Méndez, A.; Pérez-Maldonado, Y.; Domínguez-Osante, C.

2015-05-01

Tunable lenses have attracted much attention due to their potential applications in such areas like machine vision, laser projection, ophthalmology, etc. In this work we present the design of a tunable opto-mechatronic system capable of focusing and to regulate the entrance illumination that mimics the performance made by the iris and the crystalline lens of the human eye. A solid elastic lens made of PDMS has been used in order to mimic the crystalline lens and an automatic diaphragm has been used to mimic the iris of the human eye. Also, a characterization of such system has been performed with standard values of luminosity for the human eye have been taken into account to calibrate and to validate the entrance illumination levels to the overall optical system.

Delineation of Chondroid Lipoma: An Immunohistochemical and Molecular Biological Analysis

PubMed Central

de Vreeze, Ronald S. A.; van Coevorden, Frits; Boerrigter, Lucie; Nederlof, Petra M.; Haas, Rick L.; Bras, Johannes; Rosenwald, Andreas; Mentzel, Thomas; de Jong, Daphne

2011-01-01

Aims. Chondroid lipoma (CL) is a benign tumor that mimics a variety of soft tissue tumors and is characterized by translocation t(11;16). Here, we analyze CL and its histological mimics. Methods. CL (n = 4) was compared to a variety of histological mimics (n = 83) for morphological aspects and immunohistochemical features including cyclinD1(CCND1). Using FISH analysis, CCND1 and FUS were investigated as potential translocation partners. Results. All CLs were strongly positive for CCND1. One of 4 myoepitheliomas, CCND1, was positive. In well-differentiated lipomatous tumors and in chondrosarcomas, CCND1 was frequently expressed, but all myxoid liposarcomas were negative. FISH analysis did not give support for direct involvement of CCND1 and FUS as translocation partners. Conclusions. Chondroid lipoma is extremely rare and has several and more prevalent histological mimics. The differential diagnosis of chondroid lipomas can be unraveled using immunohistochemical and molecular support. PMID:21559269

The evolution of mimicry under constraints.

PubMed

Holen, Øistein Haugsten; Johnstone, Rufus A

2004-11-01

The resemblance between mimetic organisms and their models varies from near perfect to very crude. One possible explanation, which has received surprisingly little attention, is that evolution can improve mimicry only at some cost to the mimetic organism. In this article, an evolutionary game theory model of mimicry is presented that incorporates such constraints. The model generates novel and testable predictions. First, Batesian mimics that are very common and/or mimic very weakly defended models should evolve either inaccurate mimicry (by stabilizing selection) or mimetic polymorphism. Second, Batesian mimics that are very common and/or mimic very weakly defended models are more likely to evolve mimetic polymorphism if they encounter predators at high rates and/or are bad at evading predator attacks. The model also examines how cognitive constraints acting on signal receivers may help determine evolutionarily stable levels of mimicry. Surprisingly, improved discrimination abilities among signal receivers may sometimes select for less accurate mimicry.

PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana.

PubMed

Wang, Li; Wu, Li Min; Greaves, Ian K; Zhu, Anyu; Dennis, Elizabeth S; Peacock, W James

2017-04-25

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are almost completely homozygous with chromosome segments from each parent. Four particular chromosomal segments from C24 and 8 from L er were present in all of the hybrid mimic lines, whereas in the F6 small phenotype line, the 12 segments were each derived from the alternative parent. Loci critical for promoting hybrid vigor may be contained in each of these 12 conserved segments. We have identified genes with similar altered expression in hybrid mimics and F1 plants but not in the small phenotype line. These genes may be critical for the generation of hybrid vigor. Analysis of transcriptomes indicated that increased expression of the transcription factor PHYTOCHROME-INTERACTING FACTOR (PIF4) may contribute to hybrid vigor by targeting the auxin biosynthesis gene YUCCA8 and the auxin signaling gene IAA29 A number of auxin responsive genes promoting leaf growth were up-regulated in the F1 hybrids and hybrid mimics, suggesting that increased auxin biosynthesis and signaling contribute to the hybrid phenotype. The hybrid mimic seeds had earlier germination as did the seeds of the F1 hybrids, indicating cosegregation of the genes for rosette size and the germination trait. Early germination may be an indicator of vigorous hybrids.

Hybrid mimics and hybrid vigor in Arabidopsis

PubMed Central

Wang, Li; Greaves, Ian K.; Groszmann, Michael; Wu, Li Min; Dennis, Elizabeth S.; Peacock, W. James

2015-01-01

F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID:26283378

miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

PubMed

Tian, Yunhong; Cai, Longmei; Tian, Yunming; Tu, Yinuo; Qiu, Huizhi; Xie, Guofeng; Huang, Donglan; Zheng, Ronghui; Zhang, Weijun

2016-01-01

MicroRNAs (miRNAs) have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA) is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT) is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC). We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

PubMed

Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Martínez-Máñez, Ramón; Sancenón, Félix

2014-11-21

A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e. (i) a nucleophilic phenol group able to undergo phosphorylation with nerve gases, (ii) a carbonyl group as a reactive site for cyanide; and (iii) a triisopropylsilyl (TIPS) protecting group that is known to react with fluoride. The reaction of P4 with DCNP in acetonitrile resulted in both the phosphorylation of the phenoxy group and the release of cyanide, which was able to react with the carbonyl group of P4 to produce a colour modulation from pink to orange. In contrast, phosphorylation of P4 with DFP in acetonitrile released fluoride that hydrolysed the TIPS group in P4 to yield a colour change from pink to blue. Probe P4 was able to discriminate between DFP and DCNP with remarkable sensitivity; limits of detection of 0.36 and 0.40 ppm for DCNP and DFP, respectively, were calculated. Besides, no interference from other organophosphorous derivatives or with presence of acid was observed. The sensing behaviour of P4 was also retained when incorporated into silica gel plates or onto polyethylene oxide membranes, which allowed the development of simple test strips for the colorimetric detection of DCNP and DFP in the vapour phase. P4 is the first probe capable of colorimetrically differentiating between a Tabun mimic (DCNP) and a Sarin and Soman mimic (DFP).

PIF4-controlled auxin pathway contributes to hybrid vigor in Arabidopsis thaliana

PubMed Central

Wang, Li; Wu, Li Min; Greaves, Ian K.; Zhu, Anyu; Dennis, Elizabeth S.; Peacock, W. James

2017-01-01

F1 hybrids in Arabidopsis and crop species are uniform and high yielding. The F2 generation loses much of the yield advantage and the plants have heterogeneous phenotypes. We generated pure breeding hybrid mimic lines by recurrent selection and also selected a pure breeding small phenotype line. The hybrid mimics are almost completely homozygous with chromosome segments from each parent. Four particular chromosomal segments from C24 and 8 from Ler were present in all of the hybrid mimic lines, whereas in the F6 small phenotype line, the 12 segments were each derived from the alternative parent. Loci critical for promoting hybrid vigor may be contained in each of these 12 conserved segments. We have identified genes with similar altered expression in hybrid mimics and F1 plants but not in the small phenotype line. These genes may be critical for the generation of hybrid vigor. Analysis of transcriptomes indicated that increased expression of the transcription factor PHYTOCHROME-INTERACTING FACTOR (PIF4) may contribute to hybrid vigor by targeting the auxin biosynthesis gene YUCCA8 and the auxin signaling gene IAA29. A number of auxin responsive genes promoting leaf growth were up-regulated in the F1 hybrids and hybrid mimics, suggesting that increased auxin biosynthesis and signaling contribute to the hybrid phenotype. The hybrid mimic seeds had earlier germination as did the seeds of the F1 hybrids, indicating cosegregation of the genes for rosette size and the germination trait. Early germination may be an indicator of vigorous hybrids. PMID:28396418

77 FR 66836 - Notice of Receipt of Pesticide Products; Registration Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-07

... Pheromone Mimic (7,9,11-Dodecatrien-1-ol, formate at 90.8%. Product Type: Pheromone (Mating Disruptor... (Mating Disruptor) with Carob Moth Pheromone Mimic (7,9,11-Dodecatrien-1-ol, formate at 2%. Product Type...

Tough Ceramic Mimics Mother of Pearl

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

Ritchie, Robert

2008-12-05

Berkeley Lab scientists have mimicked the structure of mother of pearl to create what may well be the toughest ceramic ever produced. http://newscenter.lbl.gov/press-releases/2008/12/05/scientists-create-tough-ceramic-that-mimics-mother-of-pearl/

Tough Ceramic Mimics Mother of Pearl

ScienceCinema

Ritchie, Robert

2017-12-12

Berkeley Lab scientists have mimicked the structure of mother of pearl to create what may well be the toughest ceramic ever produced. http://newscenter.lbl.gov/press-releases/2008/12/05/scientists-create-tough-ceramic-that-mimics-mother-of-pearl/

A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

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

Lin, Chaoyang; Zhang, Pengju; Jiang, Anli

C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover,more » C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.« less

The immune impact of mimic endoscopic retrograde appendicitis therapy and appendectomy on rabbits of acute appendicitis.

PubMed

Liu, Suqin; Pei, Fenghua; Wang, Xinhong; Li, Deliang; Zhao, Lixia; Song, Yanyan; Chen, Zhendong; Liu, Bingrong

2017-09-12

This study was conducted to evaluate the immune impact of mimic endoscopic retrograde appendicitis therapy and appendectomy on rabbits of acute suppurative appendicitis and to determine whether TLR4/MYD88/NF-κB signaling pathway was activated in this process. 48 rabbits were assigned into 4 groups: group I, the mimic endoscopic retrograde appendicitis therapy group; group II, the appendectomy group; group III, the model group; and group IV, the blank group. White blood cells decreased, while levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-4, and interleukin-10 increased on the 2 nd day in group I and II. IgA in feces decreased at 2 weeks, while fecal microbiota changed at 2 and 4 weeks after appendectomy. CD8 + cells in appendix of group I increased within 8 weeks. Upregulated expression of TLR4, MYD88, and nuclear NF-κB were detected on the 2 nd day in group I and II. Mimic endoscopic retrograde appendicitis therapy and appendectomy are effective ways for acute suppurative appendicitis. Mimic endoscopic retrograde appendicitis therapy was more preferable due to its advantage in maintaining intestinal immune function. TLR4/MYD88/NF-κB signaling pathway was activated in acute phase of appendicitis.

Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

PubMed Central

Huang, Suning; Rong, Minhua; Dang, Yiwu

2014-01-01

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC. PMID:24895573

Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.

PubMed

Huang, Suning; He, Rongquan; Rong, Minhua; Dang, Yiwu; Chen, Gang

2014-01-01

Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

Gene-specific cell labeling using MiMIC transposons

PubMed Central

Gnerer, Joshua P.; Venken, Koen J. T.; Dierick, Herman A.

2015-01-01

Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. PMID:25712101

Targeted Radiotherapy of Estrogen Receptor Positive Tumors

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

Raghavan Rajagopalan

The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful formore » targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.« less

Signals, cues and the nature of mimicry

PubMed Central

2017-01-01

‘Mimicry’ is used in the evolutionary and ecological literature to describe diverse phenomena. Many are textbook examples of natural selection's power to produce stunning adaptations. However, there remains a lack of clarity over how mimetic resemblances are conceptually related to each other. The result is that categories denoting the traditional subdivisions of mimicry are applied inconsistently across studies, hindering attempts at conceptual unification. This review critically examines the logic by which mimicry can be conceptually organized and analysed. It highlights the following three evolutionarily relevant distinctions. (i) Are the model's traits being mimicked signals or cues? (ii) Does the mimic signal a fitness benefit or fitness cost in order to manipulate the receiver's behaviour? (iii) Is the mimic's signal deceptive? The first distinction divides mimicry into two broad categories: ‘signal mimicry’ and ‘cue mimicry’. ‘Signal mimicry’ occurs when mimic and model share the same receiver, and ‘cue mimicry’ when mimic and model have different receivers or when there is no receiver for the model's trait. ‘Masquerade’ fits conceptually within cue mimicry. The second and third distinctions divide both signal and cue mimicry into four types each. These are the three traditional mimicry categories (aggressive, Batesian and Müllerian) and a fourth, often overlooked category for which the term ‘rewarding mimicry’ is suggested. Rewarding mimicry occurs when the mimic's signal is non-deceptive (as in Müllerian mimicry) but where the mimic signals a fitness benefit to the receiver (as in aggressive mimicry). The existence of rewarding mimicry is a logical extension of the criteria used to differentiate the three well-recognized forms of mimicry. These four forms of mimicry are not discrete, immutable types, but rather help to define important axes along which mimicry can vary. PMID:28202806

Artificial photosynthesis using chlorophyll based carotenoid quinone triads: A brief synopsis of research progress as of 31 December 1986

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

Gust, D.; Moore, T.A.

1986-12-31

The design, synthesis and study of a series of carotenoid-chlorophyll-quinone triad molecules which mimic some of the basic photochemistry and photophysics of natural photosynthesis is sought. The first members of this series have now been prepared, and have been found to mimic photosynthetic charge separation, carotenoid antenna function, and carotenoid photoprotection from singlet oxygen damage. Although the triad molecules mimic the general principle of multistep electron transfer which is found in natural photosynthesis, the details of photosynthetic electron transfer differ in the triads, in that the first electron transfer step involves electron donation from the excited state donor, followed bymore » reduction of the resulting donor radical cation by the carotenoid. In photosynthesis, the electron is moved through several acceptors before the chlorophyll radical cation is reduced. Therefore, our recent work has concentrated on the design and synthesis of new model systems which better mimic certain aspects of natural photosynthesis.« less

A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

PubMed

Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

2016-07-25

Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

Approaches to efficient molecular catalyst systems for photochemical H2 production using [FeFe]-hydrogenase active site mimics.

PubMed

Wang, Mei; Chen, Lin; Li, Xueqiang; Sun, Licheng

2011-12-28

The research on structural and functional biomimics of the active site of [FeFe]-hydrogenases is in an attempt to elucidate the mechanisms of H(2)-evolution and uptake at the [FeFe]-hydrogenase active site, and to learn from Nature how to create highly efficient H(2)-production catalyst systems. Undoubtedly, it is a challenging, arduous, and long-term work. In this perspective, the progresses in approaches to photochemical H(2) production using mimics of the [FeFe]-hydrogenase active site as catalysts in the last three years are reviewed, with emphasis on adjustment of the redox potentials and hydrophilicity of the [FeFe]-hydrogenase active site mimics to make them efficient catalysts for H(2) production. With gradually increasing understanding of the chemistry of the [FeFe]-hydrogenases and their mimics, more bio-inspired proton reduction catalysts with significantly improved efficiency of H(2) production will be realized in the future. This journal is © The Royal Society of Chemistry 2011

Instructions to mimic improve facial emotion recognition in people with sub-clinical autism traits.

PubMed

Lewis, Michael B; Dunn, Emily

2017-11-01

People tend to mimic the facial expression of others. It has been suggested that this helps provide social glue between affiliated people but it could also aid recognition of emotions through embodied cognition. The degree of facial mimicry, however, varies between individuals and is limited in people with autism spectrum conditions (ASC). The present study sought to investigate the effect of promoting facial mimicry during a facial-emotion-recognition test. In two experiments, participants without an ASC diagnosis had their autism quotient (AQ) measured. Following a baseline test, they did an emotion-recognition test again but half of the participants were asked to mimic the target face they saw prior to making their responses. Mimicry improved emotion recognition, and further analysis revealed that the largest improvement was for participants who had higher scores on the autism traits. In fact, recognition performance was best overall for people who had high AQ scores but also received the instruction to mimic. Implications for people with ASC are explored.

Convergent evolution and mimicry of protein linear motifs in host-pathogen interactions.

PubMed

Chemes, Lucía Beatriz; de Prat-Gay, Gonzalo; Sánchez, Ignacio Enrique

2015-06-01

Pathogen linear motif mimics are highly evolvable elements that facilitate rewiring of host protein interaction networks. Host linear motifs and pathogen mimics differ in sequence, leading to thermodynamic and structural differences in the resulting protein-protein interactions. Moreover, the functional output of a mimic depends on the motif and domain repertoire of the pathogen protein. Regulatory evolution mediated by linear motifs can be understood by measuring evolutionary rates, quantifying positive and negative selection and performing phylogenetic reconstructions of linear motif natural history. Convergent evolution of linear motif mimics is widespread among unrelated proteins from viral, prokaryotic and eukaryotic pathogens and can also take place within individual protein phylogenies. Statistics, biochemistry and laboratory models of infection link pathogen linear motifs to phenotypic traits such as tropism, virulence and oncogenicity. In vitro evolution experiments and analysis of natural sequences suggest that changes in linear motif composition underlie pathogen adaptation to a changing environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

PubMed

Zwanenburg, Binne; Nayak, Sandip K; Charnikhova, Tatsiana V; Bouwmeester, Harro J

2013-09-15

Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Simplified Approach to Encephalitis and Its Mimics: Key Clinical Decision Points in the Setting of Specific Imaging Abnormalities.

PubMed

McKnight, Colin D; Kelly, Aine M; Petrou, Myria; Nidecker, Anna E; Lorincz, Matthew T; Altaee, Duaa K; Gebarski, Stephen S; Foerster, Bradley

2017-06-01

Infectious encephalitis is a relatively common cause of morbidity and mortality. Treatment of infectious encephalitis with antiviral medication can be highly effective when administered promptly. Clinical mimics of encephalitis arise from a broad range of pathologic processes, including toxic, metabolic, neoplastic, autoimmune, and cardiovascular etiologies. These mimics need to be rapidly differentiated from infectious encephalitis to appropriately manage the correct etiology; however, the many overlapping signs of these various entities present a challenge to accurate diagnosis. A systematic approach that considers both the clinical manifestations and the imaging findings of infectious encephalitis and its mimics can contribute to more accurate and timely diagnosis. Following an institutional review board approval, a health insurance portability and accountability act (HIPAA)-compliant search of our institutional imaging database (teaching files) was conducted to generate a list of adult and pediatric patients who presented between January 1, 1995 and October 10, 2013 for imaging to evaluate possible cases of encephalitis. Pertinent medical records, including clinical notes as well as surgical and pathology reports, were reviewed and correlated with imaging findings. Clinical and imaging findings were combined to generate useful flowcharts designed to assist in distinguishing infectious encephalitis from its mimics. Key imaging features were reviewed and were placed in the context of the provided flowcharts. Four flowcharts were presented based on the primary anatomic site of imaging abnormality: group 1: temporal lobe; group 2: cerebral cortex; group 3: deep gray matter; and group 4: white matter. An approach that combines features on clinical presentation was then detailed. Imaging examples were used to demonstrate similarities and key differences. Early recognition of infectious encephalitis is critical, but can be quite complex due to diverse pathologies and overlapping features. Synthesis of both the clinical and imaging features of infectious encephalitis and its mimics is critical to a timely and accurate diagnosis. The use of the flowcharts presented in this article can further enable both clinicians and radiologists to more confidently differentiate encephalitis from its mimics and improve patient care. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

MicroRNA-146a suppresses rheumatoid arthritis fibroblast-like synoviocytes proliferation and inflammatory responses by inhibiting the TLR4/NF-kB signaling

PubMed Central

Liu, Wei; Wu, Yuan-Hao; Zhang, Lei; Xue, Bin; Wang, Yi; Liu, Bin; Liu, Xiao-Ya; Zuo, Fang; Yang, Xiao-Yan; Chen, Fu-Yu; Duan, Ran; Cai, Yue; Zhang, Bo; Ji, Yang

2018-01-01

This study investigated whether microRNA-146a (miR-146a) mediating TLR4/NF-κB pathway affected proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes from 12 RA patients (RA-FLSs). FLSs in the logarithmic growth phase were assigned into the control, miR-146a mimic miR-146a inhibitor, Tak-242 (treated with TLR4/NF-κB pathway inhibitor) and mimic + lipopolysaccharide (LPS) groups. Cell proliferation and apoptosis were detected using CCK-8 assay and flow cytometry. The expression of miR-146a, TLR4/NF-κB pathway-related proteins and cytokines were determined by RT-qPCR, western blotting and ELISA, and the release of NO by Greiss reaction. RA rat models were constructed and the primary cells were classified into the control, negative control (NC), miR-146a mimic, miR-146a inhibitor, Tak-242, mimic + LPS, and TLR4 groups. Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen (PCNA) and intercellular adhesion molecular-1 (ICAM-1). The results showed that miR-146a levels were lower in RA-FLSs than control fibroblasts. miR-146a mimic and Tak-242 decreased RA-FLS proliferation and increased RA-FLS apoptosis, while miR-146a inhibitor had an opposite trend. miR-146a mimic and Tak-242 also decreased expression of TLR4, NF-κB, IL-1β, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, and iNOS, as well as reduced NO level in RA-FLSs while miR-146a inhibitor and TLR4 increased them. TLR4 and NF-κB levels and the positive rates of PCNA and ICAM-1 expressions were lower in RA-FLSs from RA rats given miR-146a mimic from control or miR-146a inhibitor-treated rats. These results suggest that miR-146a inhibits the proliferation and inflammatory response of RA-FLSs by down-regulating TLR4/NF-κB pathway.

Polymerization Behavior of Hydrophilic-Rich Phase of Dentin Adhesive

PubMed Central

Abedin, F.; Parthasarathy, R.; Misra, A.; Spencer, P.

2015-01-01

The 2-fold objectives of this study were 1) to understand whether model hydrophobic- and hydrophilic-rich phase mimics of dentin adhesive polymerize similarly and 2) to determine which factor, the dimethacrylate component, bisphenol A glycerolate dimethacrylate (BisGMA) or photoinitiator concentration, has greater influence on the polymerization of the hydrophilic-rich phase mimic. Current dentin adhesives are sensitive to moisture, as evidenced by nanoleakage in the hybrid layer and phase separation into hydrophobic- and hydrophilic-rich phases. Phase separation leads to limited availability of the cross-linkable dimethacrylate monomer and hydrophobic photoinitiators within the hydrophilic-rich phase. Model hydrophobic-rich phase was prepared as a single-phase solution by adding maximum wt% deuterium oxide (D2O) to HEMA/BisGMA neat resins containing 45 wt% 2-hydroxyethyl methacrylate (HEMA). Mimics of the hydrophilic-rich phase were prepared similarly but using HEMA/BisGMA neat resins containing 95, 99, 99.5, and 100 wt% HEMA. The hydrophilic-rich mimics were prepared with standard or reduced photoinitiator content. The photoinitiator systems were camphorquinone (CQ)/ethyl 4-(dimethylamino)benzoate (EDMAB) with or without [3-(3, 4-dimethyl-9-oxo-9H-thioxanthen-2-yloxy)-2-hydroxypropyl]trimethylammonium chloride (QTX). The polymerization kinetics was monitored using a Fourier transform infrared spectrophotometer with a time-resolved collection mode. The hydrophobic-rich phase exhibited a significantly higher polymerization rate compared with the hydrophilic-rich phase. Postpolymerization resulting in the secondary rate maxima was observed for the hydrophilic-rich mimic. The hydrophilic-rich mimics with standard photoinitiator concentration but varying cross-linker (BisGMA) content showed postpolymerization and a substantial degree of conversion. In contrast, the corresponding formulations with reduced photoinitiator concentrations exhibited lower polymerization and inhibition/delay of postpolymerization within 2 h. Under conditions relevant to the wet, oral environment, photoinitiator content plays an important role in the polymerization of the hydrophilic-rich phase mimic. Since the hydrophilic-rich phase is primarily water and monomethacrylate monomer (e.g., HEMA as determined previously), substantial polymerization is important to limit the potential toxic response from HEMA leaching into the surrounding tissues. PMID:25576471

Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks

PubMed Central

Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo

2016-01-01

We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

High lipophilicity of meta Mn(III) N-alkylpyridylporphyrin-based SOD mimics compensates for their lower antioxidant potency and makes them equally effective as ortho analogues in protecting SOD-deficient E. coli

PubMed Central

Kos, Ivan; Benov, Ludmil; Spasojević, Ivan; Rebouças, Júlio S.; Batinić-Haberle, Ines

2009-01-01

Lipophilicity/bioavailibility of Mn(III)N-alkylpyridylporphyrin-based SOD mimics has major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues, but are 10-fold more lipophilic and more planar. Enhanced lipophilicity contributes to their higher accumulation in cytosol of SOD-deficient E. coli, compensating for their lower potency; consequently both isomers exert similar-to-identical protection of SOD-deficient E. coli. Thus meta isomers may be as prospective therapeutics as are ortho porphyrins. PMID:19954250

TRANSGENERATIONAL EFFECTS OF A JUVENILE HORMONE MIMIC ON THE ESTUARINE MYSID, MYSIDOPSIS BAHIA (CRUSTACEA: MYSIDACEA)

EPA Science Inventory

Fenoxycarb is a juvenile hormone (JH) mimic used to control insect pests by interfering with reproductive and developmental processes mediated by JH. Crustaceans are ideal organisms to monitor environmental effects of these endocrine disruptors, since they are dominant aquatic ar...

Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

PubMed

Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

2017-10-28

Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate after one injection of formulations (5mg/kg, 10mg/kg or 15mg/kg) demonstrated better efficacy at lower dose for PolyDOX. Analysis of Kaplan Meier curve was in favor of both formulations in their treatment-dose. Pathological and hematological surveys of mice treated with both formulations did not show considerable difference except for a small atrophy in liver observed after successive administration of Doxil-mimic. It could be concluded that PolyDOX can potentially limit off-site effects of Doxil due to its biodegradability and sustained release properties while it exhibited favorable safety profile comparable to Doxil. Copyright © 2017 Elsevier B.V. All rights reserved.

Tri-modal confocal mosaics detect residual invasive squamous cell carcinoma in Mohs surgical excisions

NASA Astrophysics Data System (ADS)

Gareau, Dan; Bar, Anna; Snaveley, Nicholas; Lee, Ken; Chen, Nathaniel; Swanson, Neil; Simpson, Eric; Jacques, Steve

2012-06-01

For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4× histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues.

Tri-modal confocal mosaics detect residual invasive squamous cell carcinoma in Mohs surgical excisions

PubMed Central

Bar, Anna; Snaveley, Nicholas; Lee, Ken; Chen, Nathaniel; Swanson, Neil; Simpson, Eric; Jacques, Steve

2012-01-01

Abstract. For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4× histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues. PMID:22734774

MiR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression.

PubMed

Chen, Zheng-Gang; Zheng, Chuan-Yi; Cai, Wang-Qing; Li, Da-Wei; Ye, Fu-Yue; Zhou, Jian; Wu, Ran; Yang, Kun

2017-08-11

Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA (miR)-26b/cyclooxygenase (COX)-2 axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased level of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting miR-26b mimic into U-373 cells. The invasive cell number and wounld closing rate were reduced in U-373 cells transfected with miR-26b mimic. Besides, COX2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume and the expression of matrix metalloproteinase (MMP)-2, MMP-9). Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for treatment of glioma.

Gene-specific cell labeling using MiMIC transposons.

PubMed

Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A

2015-04-30

Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

26 CFR 1.1092(d)-2 - Personal property.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) INCOME TAXES (CONTINUED) Wash Sales of Stock Or Securities § 1.1092(d)-2 Personal property. (a... principal holdings mimic the performance of the stocks included in the stock index (or alternatively a portfolio of stocks whose performance mimics the performance of the stocks included in the stock index). [T...

Biomolecular Programming of Discrete Nanomaterials for Sensors, Templates and Mimics of Natural Nanoscale Assemblies

DTIC Science & Technology

2016-10-17

AFRL-AFOSR-VA-TR-2016-0343 BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS, TEMPLATES AND MIMICS OF NATURAL NANOSCALE ASSEMBLIES...Performance 3. DATES COVERED (From - To) 01 Jun 2011 to 31 May 2016 4. TITLE AND SUBTITLE BIOMOLECULAR PROGRAMMING OF DISCRETE NANOMATERIALS FOR SENSORS

Artificial synthetic Mn(IV)Ca-oxido complexes mimic the oxygen-evolving complex in photosystem II.

PubMed

Chen, Changhui; Zhang, Chunxi; Dong, Hongxing; Zhao, Jingquan

2015-03-14

A novel family of heteronuclear Mn(IV)Ca-oxido complexes containing Mn(IV)Ca-oxido cuboidal moieties and reactive water molecules on Ca(2+) have been synthesized and characterized to mimic the oxygen-evolving complex (OEC) of photosystem II (PSII) in nature.

Malware Mimics for Network Security Assessment

DTIC Science & Technology

2011-03-01

Master’s Thesis 4 . TITLE AND SUBTITLE Malware Mimics for Network Security Assessment 6. AUTHOR(S) Taff, William R and Salevski, Paul M. 5...Communication Protocol .......................41 viii 4 . Graphical User Interface for MM-Server .......43 C. BUILDING THE TEST PLATFORM...Extension ...............71 2. More Advanced Modules ........................72 3. Increase Scale of Test Bed ...................73 4 . Security

Effects of spray mixtures on droplet size under aerial application conditions and implications on drift

USDA-ARS?s Scientific Manuscript database

The use of simulated and mimic sprays for atomization studies in high speed wind tunnels allows researchers to limit the amount of active ingredients used in spray tests; however, it is important that these simulated and mimic sprays have the same physical and atomization characteristics of spray co...

Multidimensional Extension of Multiple Indicators Multiple Causes Models to Detect DIF

ERIC Educational Resources Information Center

Lee, Soo; Bulut, Okan; Suh, Youngsuk

2017-01-01

A number of studies have found multiple indicators multiple causes (MIMIC) models to be an effective tool in detecting uniform differential item functioning (DIF) for individual items and item bundles. A recently developed MIMIC-interaction model is capable of detecting both uniform and nonuniform DIF in the unidimensional item response theory…

THE USE OF GENE ARRAYS TO MEASURE CHANGES IN GENE EXPRESSION PATTERNS IN FISH EXPOSED TO COMPOUNDS THAT MIMIC ESTROGEN

EPA Science Inventory

We have developed estrogen-sensitive gene arrays to measure changes in gene expression in sheepshead minnows and largemouth bass exposed to anthropogenic chemicals that mimic estrogen. The in vivo exposures, which realize the full physiological response in fish, result in changes...

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

ERIC Educational Resources Information Center

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

MicroRNA-96 Promotes Tumor Invasion in Colorectal Cancer via RECK.

PubMed

Iseki, Yasuhito; Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Hirakawa, Kosei; Ohira, Masaichi

2018-04-01

miR-96 is reported to inhibit reversion cysteine-rich Kazal motif (RECK), which is associated with tumor invasion, in solid cancer types (e.g. breast cancer, non-small cell lung cancer, esophageal cancer). The purpose of this study is to clarify whether miR-96 is similarly associated with tumor invasion in colorectal cancer. We performed western blotting to investigate the expression of RECK when miR-96 mimics or inhibitors were transferred into HCT-116 colorectal cancer cells. The RECK mRNA level was assessed by a reverse transcription polymerase chain reaction. An invasion assay was used to evaluate tumor invasion. The expression of RECK was inhibited by the transfection of miR-96 mimics. RECK mRNA level was reduced by miR-96 mimics and increased by miR-96 inhibitor. In the invasion assay, miR-96 mimics were shown to promote tumor invasion. miR-96 may be associated with tumor invasion through inhibition of RECK expression in colorectal cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Molecular mimicry modulates plant host responses to pathogens.

PubMed

Ronald, Pamela; Joe, Anna

2018-01-25

Pathogens often secrete molecules that mimic those present in the plant host. Recent studies indicate that some of these molecules mimic plant hormones required for development and immunity. This Viewpoint reviews the literature on microbial molecules produced by plant pathogens that functionally mimic molecules present in the plant host. This article includes examples from nematodes, bacteria and fungi with emphasis on RaxX, a microbial protein produced by the bacterial pathogen Xanthomonas oryzae pv. oryzae. RaxX mimics a plant peptide hormone, PSY (plant peptide containing sulphated tyrosine). The rice immune receptor XA21 detects sulphated RaxX but not the endogenous peptide PSY. Studies of the RaxX/XA21 system have provided insight into both host and pathogen biology and offered a framework for future work directed at understanding how XA21 and the PSY receptor(s) can be differentially activated by RaxX and endogenous PSY peptides. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Spectacular Batesian mimicry in ants

NASA Astrophysics Data System (ADS)

Ito, Fuminori; Hashim, Rosli; Huei, Yek Sze; Kaufmann, Eva; Akino, Toshiharu; Billen, Johan

2004-10-01

The mechanism by which palatable species take advantage of their similarity in appearance to those that are unpalatable, in order to avoid predation, is called Batesian mimicry. Several arthropods are thought to be Batesian mimics of social insects; however, social insects that are Batesian mimics among themselves are rare. In Malaysia we found a possible Batesian mimic in an arboreal ant species, Camponotus sp., which was exclusively observed on foraging trails of the myrmicine ant Crematogaster inflata. The bright yellow and black colouring pattern, as well as the walking behaviour, were very similar in both species. We observed general interactions between the two species, and tested their palatability and the significance of the remarkably similar visual colour patterns for predator avoidance. Prey offered to C. inflata was also eaten by Camponotus workers in spite of their being attacked by C. inflata, indicating that Camponotus sp. is a commensal of C. inflata. An experiment with chicks as potential predators suggests that Camponotus sp. is palatable whereas C. inflata is unpalatable. After tasting C. inflata, the chicks no longer attacked Camponotus sp., indicating that Camponotus sp. is a Batesian mimic of Crematogaster inflata.

Widespread long noncoding RNAs as endogenous target mimics for microRNAs in plants.

PubMed

Wu, Hua-Jun; Wang, Zhi-Min; Wang, Meng; Wang, Xiu-Jie

2013-04-01

Target mimicry is a recently identified regulatory mechanism for microRNA (miRNA) functions in plants in which the decoy RNAs bind to miRNAs via complementary sequences and therefore block the interaction between miRNAs and their authentic targets. Both endogenous decoy RNAs (miRNA target mimics) and engineered artificial RNAs can induce target mimicry effects. Yet until now, only the Induced by Phosphate Starvation1 RNA has been proven to be a functional endogenous microRNA target mimic (eTM). In this work, we developed a computational method and systematically identified intergenic or noncoding gene-originated eTMs for 20 conserved miRNAs in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). The predicted miRNA binding sites were well conserved among eTMs of the same miRNA, whereas sequences outside of the binding sites varied a lot. We proved that the eTMs of miR160 and miR166 are functional target mimics and identified their roles in the regulation of plant development. The effectiveness of eTMs for three other miRNAs was also confirmed by transient agroinfiltration assay.

Gibberellic and kaurenoic hybrid strigolactone mimics for seed germination of parasitic weeds.

PubMed

Pereira, Rondinelle G; Cala, Antonio; Fernández-Aparicio, Mónica; Molinillo, José Mg; Boaventura, Maria Ad; Macías, Francisco A

2017-12-01

Parasitic weeds are widespread and cause significant losses in important crops. Their germination requires the detection of crop-derived molecules such as strigolactones. Strigolactone mimics are germination-inducing molecules with the potential to apply a suicidal germination strategy for seed bank control of parasitic weeds. The D-ring, which is instrumental in the germination process of seeds of parasitic weeds, was attached to gibberellin (GA 3 ) and kaurenoic acid as the scaffold. It was shown that indeed strigolactone mimics prepared from GA 3 and kaurenoic acid are active as stimulants when a D-ring is present; some of the mimics are as active as GR24. The starting molecules were plant hormones that had previous growth-regulating activity in other organisms and the products showed enhanced activity towards parasitic weeds. The information generated may contribute to a better understanding of the germination biochemistry of the weed species used. Further research is required in this area but it is clear that the results are promising. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

PubMed Central

Tovmasyan, Artak; Reboucas, Julio S.

2014-01-01

Abstract Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Critical Issues and Future Directions: Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution. Antioxid. Redox Signal. 20, 2416–2436. PMID:23964890

Effects of model-mimic frequency on insect visitation and plant reproduction in a self-mimicry pollination system

PubMed Central

Oleques, Suiane Santos; Marciniak, Brisa; Ribeiro, José Ricardo I

2017-01-01

Abstract The proportion of mimics and models is a key parameter in mimetic systems. In monoecious plants with self-mimicry pollination systems, the mimic-model ratio is determined by the floral sex ratio. While an equal sex ratio (1:1) could provide the perfect balance between pollen donors and stigma surfaces able to receive the pollen, an unequal ratio could increase pollination by production of a greater number of rewarding, model flowers. The aim of the present study is to test the differences in visitation frequency and reproductive rates of different mimic and model flower arrays in order to assess the efficacy of the mimetic system in a Begonia cucullata population. The frequencies of visitors to groups of flowers with three distinctive sex ratio arrays (male-biased, female-biased and equal ratio) were compared using a Bayesian approach. The reproductive outcomes were compared in order to detect advantages of particular sex ratios. Low visitation frequency was recorded in all arrays. Pollinators showed similar behaviour regardless of sex ratio; they tended to avoid female, rewardless flowers. Pollination quality was highest in the equal sex ratio array. The current study shows that sex ratio plays a critical role in the pollination of B. cucullata and that the efficacy of the self-mimicry system appears to be doubtful. Visitation frequency may be associated with visual or chemical cues that allow pollinators to recognize models and mimics, regardless of their frequency in the population. PMID:29255587

Effects of model-mimic frequency on insect visitation and plant reproduction in a self-mimicry pollination system.

PubMed

de Avila, Rubem Samuel; Oleques, Suiane Santos; Marciniak, Brisa; Ribeiro, José Ricardo I

2017-11-01

The proportion of mimics and models is a key parameter in mimetic systems. In monoecious plants with self-mimicry pollination systems, the mimic-model ratio is determined by the floral sex ratio. While an equal sex ratio (1:1) could provide the perfect balance between pollen donors and stigma surfaces able to receive the pollen, an unequal ratio could increase pollination by production of a greater number of rewarding, model flowers. The aim of the present study is to test the differences in visitation frequency and reproductive rates of different mimic and model flower arrays in order to assess the efficacy of the mimetic system in a Begonia cucullata population. The frequencies of visitors to groups of flowers with three distinctive sex ratio arrays (male-biased, female-biased and equal ratio) were compared using a Bayesian approach. The reproductive outcomes were compared in order to detect advantages of particular sex ratios. Low visitation frequency was recorded in all arrays. Pollinators showed similar behaviour regardless of sex ratio; they tended to avoid female, rewardless flowers. Pollination quality was highest in the equal sex ratio array. The current study shows that sex ratio plays a critical role in the pollination of B. cucullata and that the efficacy of the self-mimicry system appears to be doubtful. Visitation frequency may be associated with visual or chemical cues that allow pollinators to recognize models and mimics, regardless of their frequency in the population.

Metal-based superoxide dismutase and catalase mimics reduce oxidative stress biomarkers and extend life span of Saccharomyces cerevisiae.

PubMed

Ribeiro, Thales de P; Fonseca, Fernanda L; de Carvalho, Mariana D C; Godinho, Rodrigo M da C; de Almeida, Fernando Pereira; Saint'Pierre, Tatiana D; Rey, Nicolás A; Fernandes, Christiane; Horn, Adolfo; Pereira, Marcos D

2017-01-15

Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl 2 ]NO 3 , [Cu(HPClNOL)(CH 3 CN)](ClO 4 ) 2 and Mn(HPClNOL)(Cl) 2 }, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells.

PubMed

Li, Wenjuan; Cheng, Peng; Nie, Shangdan; Cui, Wen

2016-01-01

Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury.

SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways

PubMed Central

Tovmasyan, Artak; Roberts, Emily R. H.; Vujaskovic, Zeljko; Leong, Kam W.; Spasojevic, Ivan

2014-01-01

Abstract Significance: Superoxide dismutase (SOD) enzymes are indispensable and ubiquitous antioxidant defenses maintaining the steady-state levels of O2·−; no wonder, thus, that their mimics are remarkably efficacious in essentially any animal model of oxidative stress injuries thus far explored. Recent Advances: Structure-activity relationship (half-wave reduction potential [E1/2] versus log kcat), originally reported for Mn porphyrins (MnPs), is valid for any other class of SOD mimics, as it is dominated by the superoxide reduction and oxidation potential. The biocompatible E1/2 of ∼+300 mV versus normal hydrogen electrode (NHE) allows powerful SOD mimics as mild oxidants and antioxidants (alike O2·−) to readily traffic electrons among reactive species and signaling proteins, serving as fine mediators of redox-based signaling pathways. Based on similar thermodynamics, both SOD enzymes and their mimics undergo similar reactions, however, due to vastly different sterics, with different rate constants. Critical Issues: Although log kcat(O2·−) is a good measure of therapeutic potential of SOD mimics, discussions of their in vivo mechanisms of actions remain mostly of speculative character. Most recently, the therapeutic and mechanistic relevance of oxidation of ascorbate and glutathionylation and oxidation of protein thiols by MnP-based SOD mimics and subsequent inactivation of nuclear factor κB has been substantiated in rescuing normal and killing cancer cells. Interaction of MnPs with thiols seems to be, at least in part, involved in up-regulation of endogenous antioxidative defenses, leading to the healing of diseased cells. Future Directions: Mechanistic explorations of single and combined therapeutic strategies, along with studies of bioavailability and translational aspects, will comprise future work in optimizing redox-active drugs. Antioxid. Redox Signal. 20, 2372–2415. PMID:23875805

Explosives mimic for testing, training, and monitoring

DOEpatents

Reynolds, John G.; Durban, Matthew M.; Gash, Alexander E.; Grapes, Michael D.; Kelley, Ryan S.; Sullivan, Kyle T.

2018-02-13

Additive Manufacturing (AM) is used to make mimics for explosives. The process uses mixtures of explosives and matrices commonly used in AM. The explosives are formulated into a mixture with the matrix and printed using AM techniques and equipment. The explosive concentrations are kept less than 10% by wt. of the mixture to conform to requirements of shipping and handling.

Bat activity in selection harvests and intact forest canopy gaps at Indiana state forests

Treesearch

Scott Haulton; Kathryn L. DeCosta

2014-01-01

Forest managers often prescribe silvicultural methods based on how effectively they mimic the natural disturbance agents that have historically shaped the forests they manage. On Indiana state forests, selection systems are used on most harvested acreage and appear to structurally mimic the effects of naturally occurring, gap-forming disturbances affecting individual...

A novel nitrogen-dependent gene associates with the lesion mimic trait in wheat

USDA-ARS?s Scientific Manuscript database

Lesion mimic (LM) refers to hypersensitive reaction-like (HRL) symptoms that appears on leaf tissue in the absence of plant pathogens. In a wheat line P7001, LM showed up on the leaves under the 0 g nitrogen (N) treatment, but disappeared when sufficient N was supplied, suggesting that LM is N-respo...

Evaluation of MIMIC-Model Methods for DIF Testing with Comparison to Two-Group Analysis

ERIC Educational Resources Information Center

Woods, Carol M.

2009-01-01

Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for 1 group of people versus another, irrespective of mean differences on the construct. This study focuses on the use of multiple-indicator multiple-cause (MIMIC) structural equation models for DIF testing, parameterized as item…

Mixture Item Response Theory-MIMIC Model: Simultaneous Estimation of Differential Item Functioning for Manifest Groups and Latent Classes

ERIC Educational Resources Information Center

Bilir, Mustafa Kuzey

2009-01-01

This study uses a new psychometric model (mixture item response theory-MIMIC model) that simultaneously estimates differential item functioning (DIF) across manifest groups and latent classes. Current DIF detection methods investigate DIF from only one side, either across manifest groups (e.g., gender, ethnicity, etc.), or across latent classes…

Animal models of fibromyalgia

PubMed Central

2013-01-01

Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. PMID:24314231

Myositis Mimics.

PubMed

Michelle, E Harlan; Mammen, Andrew L

2015-10-01

Patients with autoimmune myositis typically present with muscle weakness, elevated serum levels of muscle enzymes, and abnormal muscle biopsies. However, patients with other acquired myopathies or genetic muscle diseases may have remarkably similar presentations. Making the correct diagnosis of another muscle disease can prevent these patients from being exposed to the risks of immunosuppressive medications, which benefit those with myositis, but not those with other types of muscle disease. Here, we review some of the most common acquired and inherited muscle diseases that can mimic autoimmune myositis, including inclusion body myositis, limb girdle muscular dystrophies, metabolic myopathies, mitochondrial myopathies, and endocrine myopathies. We emphasize aspects of the medical history, physical exam, laboratory evaluation, and muscle biopsy analysis that can help clinicians distinguish myositis mimics from true autoimmune myositis.

Artificial cell mimics as simplified models for the study of cell biology.

PubMed

Salehi-Reyhani, Ali; Ces, Oscar; Elani, Yuval

2017-07-01

Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders.

PubMed

Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

2016-04-05

Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P < 0.001) than that in the normal controls. The ADM/APB CMAP amplitude ratio was significantly reduced in the patients with distal-type CSA (P < 0.001) and the HD patients (P < 0.001) compared with that in the normal controls. The patients with distal-type CSA had significantly lower APB CMAP amplitude than the HD patients (P = 0.004). The ADM/APB CMAP amplitude ratio was significantly lower in the HD patients (P < 0.001) than that in the patients with distal-type CSA. The ADM/APB CMAP amplitude ratio of the SBMA patients was similar to that of the normal controls (P = 0.862). An absent APB CMAP and an abnormally high ADM/APB CMAP amplitude ratio (≥4.5) were observed exclusively in the ALS patients. The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

The ability of lizards to identify an artificial Batesian mimic.

PubMed

Beneš, Josef; Veselý, Petr

2017-08-01

Birds are usually considered the main predators shaping the evolution of aposematic signals and mimicry. Nevertheless, some lizards also represent predominately visually oriented predators, so they may also play an important role in the evolution of aposematism. Despite this fact, experimental evidence regarding the responses of lizards to aposematic prey is very poor compared to such evidence in birds. Lizards possess very similar sensory and cognitive abilities to those of birds and their response to aposematic prey may thus be affected by very similar processes. We investigated the reactions of a lizard, the Gran Canaria skink (Chalcides sexlineatus), to an aposematic prey and its artificial Batesian mimic. Further, we attempted to ascertain whether the lizard's food experience has any effect on its ability to recognise an artificial Batesian mimic, by using two groups of predators differing in their prior experience with the prey from which the mimic was fabricated. The red firebug (Pyrrhocoris apterus) was used as an aposematic model, and the Guyana spotted roach (Blaptica dubia) as the palatable prey from which the mimic was fabricated. The appearance of the roach was modified by a paper sticker placed on its back. The skinks showed a strong aversion towards the model firebug. They also avoided attacking the cockroaches with the firebug pattern sticker. This suggests that a visual rather than a chemical signal is responsible for this aversion. The protection provided by the firebug sticker was even effective when the skinks were familiar with unmodified cockroaches (previous food experience). Copyright © 2017 Elsevier GmbH. All rights reserved.

A sensitive colorimetric aptasensor based on trivalent peroxidase-mimic DNAzyme and magnetic nanoparticles.

PubMed

Liu, Shuwen; Xu, Naihan; Tan, Chunyan; Fang, Wei; Tan, Ying; Jiang, Yuyang

2018-08-14

In this study, a novel colorimetric aptasensor was prepared by coupling trivalent peroxidase-mimic DNAzyme and magnetic nanoparticles for highly sensitive and selective detection of target proteins. A three G-quadruplex (G4) DNA-hemin complex was employed as the trivalent peroxidase-mimic DNAzyme, in which hemin assisted the G4-DNA to fold into a catalytic conformation and act as an enzyme. The design of the aptasensor includes magnetic nanoparticles (MNPs), complementary DNA (cDNA) modified with biotin, and a label-free single strand DNA (ssDNA) including the aptamer and trivalent peroxidase-mimic DNAzyme. The trivalent DNAzyme, which has the highest catalytic activity among multivalent DNAzymes, catalyzed the H 2 O 2 -mediated oxidation of ABTS. The colorless ABTS was oxidized to produce a blue-green product that can be clearly distinguished by the naked eye. The aptamer and trivalent peroxidase-mimic DNAzyme promote the specificity and sensitivity of this detection method, which can be generalized for other targets by simply replacing the corresponding aptamers. To demonstrate the feasible use of the aptasensor for target detection, a well-known tumor biomarker MUC1 was evaluated as the model target. The limits of detection were determined to be 5.08 and 5.60 nM in a linear range of 50-1000 nM in a buffer solution and 10% serum system, respectively. This colorimetric and label-free aptasensor with excellent sensitivity and strong anti-interference ability has potential application in disease diagnoses, prognosis tracking, and therapeutic evaluation. Copyright © 2018 Elsevier B.V. All rights reserved.

Four-year follow-up of transient ischemic attacks, strokes, and mimics: a retrospective transient ischemic attack clinic cohort study.

PubMed

Dutta, Dipankar; Bowen, Emily; Foy, Chris

2015-05-01

There is limited information on outcomes from rapid access transient ischemic attack (TIA) clinics. We present 4-year outcomes of TIAs, strokes, and mimics from a UK TIA clinic database. All patients referred between April 2010 and May 2012 were retrospectively identified and outcomes determined. End points were stroke, myocardial infarction, any vascular event (TIA, stroke, or myocardial infarction), and all-cause death. Data were analyzed by survival analysis. Of 1067 patients, 31.6% were TIAs, 18% strokes, and 50.4% mimics. Median assessment time was 4.5 days from onset and follow-up was for 34.9 months. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke, and 2.0% of mimics at the end of follow-up. Stroke risk at 90 days was 1.3% for patients diagnosed as TIA or stroke. Compared with mimics, hazard ratios for subsequent stroke were 3.88 (1.90-7.91) for TIA and 5.84 (2.81-12.11) for stroke. Hazard ratio for any subsequent vascular event was 2.91 (1.97-4.30) for TIA and 2.83 (1.81-4.41) for stroke. Hazard ratio for death was 1.68 (1.10-2.56) for TIA and 2.19 (1.38-3.46) for stroke. Our results show a lower 90-day stroke incidence after TIA or minor stroke than in earlier studies, suggesting that rapid access daily TIA clinics may be having a significant effect on reducing strokes. © 2015 American Heart Association, Inc.

Investigation Gender/Ethnicity Heterogeneity in Course Management System Use in Higher Education by Utilizing the MIMIC Model

ERIC Educational Resources Information Center

Li, Yi

2012-01-01

This study focuses on the issue of learning equity in colleges and universities where teaching and learning have come to depend heavily on computer technologies. The study uses the Multiple Indicators Multiple Causes (MIMIC) latent variable model to quantitatively investigate whether there is a gender /ethnicity difference in using computer based…

Traditional adaptation to natural processes of erosion and sedimentation on Yap Island

Treesearch

Marjorie C. Falanruw

1990-01-01

Yap is a high island with a mean annual rainfall of 3040 mm and considerable potential for erosion. The island once supported a dense population with a nature-intensive technology. The traditional food production system incorporated tree gardens which mimic natural forests in intercepting rainfall and holding the soil, and taro patch system which mimic swamp forests...

The STRONG STAR Multidisciplinary PTSD Research Consortium

DTIC Science & Technology

2013-09-01

prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior...stress, prenatal corticosterone reduced TH mRNA, suggesting that prenatal stress produces its effects on TH mRNA through a mechanism dependent on...Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior

Multi-Population Invariance with Dichotomous Measures: Combining Multi-Group and MIMIC Methodologies in Evaluating the General Aptitude Test in the Arabic Language

ERIC Educational Resources Information Center

Sideridis, Georgios D.; Tsaousis, Ioannis; Al-harbi, Khaleel A.

2015-01-01

The purpose of the present study was to extend the model of measurement invariance by simultaneously estimating invariance across multiple populations in the dichotomous instrument case using multi-group confirmatory factor analytic and multiple indicator multiple causes (MIMIC) methodologies. Using the Arabic version of the General Aptitude Test…

Confabulation Based Sentence Completion for Machine Reading

DTIC Science & Technology

2010-11-01

making sentence completion an indispensible component of machine reading. Cogent confabulation is a bio-inspired computational model that mimics the...thus making sentence completion an indispensible component of machine reading. Cogent confabulation is a bio-inspired computational model that mimics...University Press, 1992. [2] H. Motoda and K. Yoshida, “Machine learning techniques to make computers easier to use,” Proceedings of the Fifteenth

Evidence for close side-chain packing in an early protein folding intermediate previously assumed to be a molten globule

PubMed Central

Rosen, Laura E.; Connell, Katelyn B.; Marqusee, Susan

2014-01-01

The molten globule, a conformational ensemble with significant secondary structure but only loosely packed tertiary structure, has been suggested to be a ubiquitous intermediate in protein folding. However, it is difficult to assess the tertiary packing of transiently populated species to evaluate this hypothesis. Escherichia coli RNase H is known to populate an intermediate before the rate-limiting barrier to folding that has long been thought to be a molten globule. We investigated this hypothesis by making mimics of the intermediate that are the ground-state conformation at equilibrium, using two approaches: a truncation to generate a fragment mimic of the intermediate, and selective destabilization of the native state using point mutations. Spectroscopic characterization and the response of the mimics to further mutation are consistent with studies on the transient kinetic intermediate, indicating that they model the early intermediate. Both mimics fold cooperatively and exhibit NMR spectra indicative of a closely packed conformation, in contrast to the hypothesis of molten tertiary packing. This result is important for understanding the nature of the subsequent rate-limiting barrier to folding and has implications for the assumption that many other proteins populate molten globule folding intermediates. PMID:25258414

Evidence for close side-chain packing in an early protein folding intermediate previously assumed to be a molten globule.

PubMed

Rosen, Laura E; Connell, Katelyn B; Marqusee, Susan

2014-10-14

The molten globule, a conformational ensemble with significant secondary structure but only loosely packed tertiary structure, has been suggested to be a ubiquitous intermediate in protein folding. However, it is difficult to assess the tertiary packing of transiently populated species to evaluate this hypothesis. Escherichia coli RNase H is known to populate an intermediate before the rate-limiting barrier to folding that has long been thought to be a molten globule. We investigated this hypothesis by making mimics of the intermediate that are the ground-state conformation at equilibrium, using two approaches: a truncation to generate a fragment mimic of the intermediate, and selective destabilization of the native state using point mutations. Spectroscopic characterization and the response of the mimics to further mutation are consistent with studies on the transient kinetic intermediate, indicating that they model the early intermediate. Both mimics fold cooperatively and exhibit NMR spectra indicative of a closely packed conformation, in contrast to the hypothesis of molten tertiary packing. This result is important for understanding the nature of the subsequent rate-limiting barrier to folding and has implications for the assumption that many other proteins populate molten globule folding intermediates.

Nanoscale biomimetics studies of Salvinia molesta for micropattern fabrication.

PubMed

Hunt, James; Bhushan, Bharat

2011-11-01

The emerging field of biomimetics allows one to take inspiration from nature and mimic it in order to create various products, devices and structures. There are a large number of objects, including bacteria, plants, land and aquatic animals and seashells, with properties of commercial interest. The subject of interest for this research is the water fern Salvinia molesta because of its ability to trap air. Air-retaining surfaces are of technological interest due to their ability to reduce drag when used for fluid transport, ship coatings and other submersible industrial products in which drag is a concern. The purpose of this research is to mimic the air trapping ability of S. molesta in order to prove that a structure can be created in the lab that can mimic the behavior of the fern as well as demonstrate microfabrication techniques that can be utilized in industry to produce such materials. In this work, a novel methodology for the fabrication of microstructures that mimic the water-pinning and air-trapping ability of S. molesta is introduced. Water contact angle, water roll angle and adhesive force of the new microstructure and water fern are investigated. Copyright © 2011 Elsevier Inc. All rights reserved.

Mimic Carbonic Anhydrase Using Metal-Organic Frameworks for CO2 Capture and Conversion.

PubMed

Jin, Chaonan; Zhang, Sainan; Zhang, Zhenjie; Chen, Yao

2018-02-19

Carbonic anhydrase (CA) is a zinc-containing metalloprotein, in which the Zn active center plays the key role to transform CO 2 into carbonate. Inspired by nature, herein we used metal-organic frameworks (MOFs) to mimic CA for CO 2 conversion, on the basis of the structural similarity between the Zn coordination in MOFs and CA active center. The biomimetic activity of MOFs was investigated by detecting the hydrolysis of para-nitrophenyl acetate, which is a model reaction used to evaluate CA activity. The biomimetic materials (e.g., CFA-1) showed good catalytic activity, and excellent reusability, and solvent and thermal stability, which is very important for practical applications. In addition, ZIF-100 and CFA-1 were used to mimic CA to convert CO 2 gas, and exhibited good efficiency on CO 2 conversion compared with those of other porous materials (e.g., MCM-41, active carbon). This biomimetic study revealed a novel CO 2 treatment method. Instead of simply using MOFs to absorb CO 2 , ZIF-100 and CFA-1 were used to mimic CA for in situ CO 2 conversion, which provides a new prospect in the biological and industrial applications of MOFs.

MicroRNA-122 mimic transfection contributes to apoptosis in HepG2 cells.

PubMed

Huang, Hongyan; Zhu, Yueyong; Li, Shaoyang

2015-11-01

There is currently a requirement for effective treatment strategies for human hepatocellular carcinoma (HCC), a leading cause of cancer‑associated mortality. MicroRNA-122 (miR-122), a repressor of the endogenous apoptosis regulator Bcl‑w, is frequently downregulated in HCC. Thus, it is hypothesized that the activation of miR‑122 may induce selective hepatocellular apoptosis via caspase activation in a model of HCC. In the present study, an miR‑122 mimic transfection was performed in HepG2 cells, and used to investigate the role and therapeutic potential of miR‑122 in the regulation of HCC‑derived cell lines. The apoptotic rates of HepG2 cells were significantly increased following miR‑122 mimic transfection. Reverse transcription‑polymerase chain reaction analysis revealed that Bcl‑w mRNA was significantly reduced, while the mRNA levels of caspase‑9 and caspase‑3 were markedly increased. The immunocytochemistry results supported the mRNA trends. Collectively, the present results suggest that endogenous miR‑122 contributes to HepG2 apoptosis and that transfection of mimic miR‑122 normalizes apoptotic levels in a model of HCC.

Widespread Long Noncoding RNAs as Endogenous Target Mimics for MicroRNAs in Plants1[W

PubMed Central

Wu, Hua-Jun; Wang, Zhi-Min; Wang, Meng; Wang, Xiu-Jie

2013-01-01

Target mimicry is a recently identified regulatory mechanism for microRNA (miRNA) functions in plants in which the decoy RNAs bind to miRNAs via complementary sequences and therefore block the interaction between miRNAs and their authentic targets. Both endogenous decoy RNAs (miRNA target mimics) and engineered artificial RNAs can induce target mimicry effects. Yet until now, only the Induced by Phosphate Starvation1 RNA has been proven to be a functional endogenous microRNA target mimic (eTM). In this work, we developed a computational method and systematically identified intergenic or noncoding gene-originated eTMs for 20 conserved miRNAs in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). The predicted miRNA binding sites were well conserved among eTMs of the same miRNA, whereas sequences outside of the binding sites varied a lot. We proved that the eTMs of miR160 and miR166 are functional target mimics and identified their roles in the regulation of plant development. The effectiveness of eTMs for three other miRNAs was also confirmed by transient agroinfiltration assay. PMID:23429259

Mimicry in plant-parasitic fungi.

PubMed

Ngugi, Henry K; Scherm, Harald

2006-04-01

Mimicry is the close resemblance of one living organism (the mimic) to another (the model), leading to misidentification by a third organism (the operator). Similar to other organism groups, certain species of plant-parasitic fungi are known to engage in mimetic relationships, thereby increasing their fitness. In some cases, fungal infection can lead to the formation of flower mimics (pseudo flowers) that attract insect pollinators via visual and/or olfactory cues; these insects then either transmit fungal gametes to accomplish outcrossing (e.g. in some heterothallic rust fungi belonging to the genera Puccinia and Uromyces) or vector infectious spores to healthy plants, thereby spreading disease (e.g. in the anther smut fungus Microbotryum violaceum and the mummy berry pathogen Monilinia vaccinii-corymbosi). In what is termed aggressive mimicry, some specialized plant-parasitic fungi are able to mimic host structures or host molecules to gain access to resources. An example is M. vaccinii-corymbosi, whose conidia and germ tubes, respectively, mimic host pollen grains and pollen tubes anatomically and physiologically, allowing the pathogen to gain entry into the host's ovary via stigma and style. We review these and other examples of mimicry by plant-parasitic fungi and some of the mechanisms, signals, and evolutionary implications.

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

Tang, Zhiwen; Wu, Hong J.; Zhang, Youyu

Ferritins are nano-scale globular protein cages encapsulating a ferric core. They widely exist in animals, plants, and microbes, playing indispensable roles in iron homeostasis. Interestingly, our study clearly demonstrates that ferritin has an enzyme-mimic activity derived from its ferric nano-core, but not the protein cage. Further study revealed that the mimic-enzyme activity of ferritin is more thermally stable and pH-tolerant compared with horseradish peroxidase. Considering the abundance of ferritin in numerous organisms, this finding may indicate a new role of ferritin in antioxidant and detoxification metabolisms. In addition, as a natural protein-caged nanoparticle with an enzyme-mimic activity, ferritin is readilymore » conjugated with biomolecules to construct nano-biosensors, thus holds promising potential for facile and biocompatible labeling for sensitive and robust bioassays in biomedical applications.« less

Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

PubMed

Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

2017-01-03

Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4.

PubMed

Guo, Yun-Bao; Ji, Tie-Feng; Zhou, Hong-Wei; Yu, Jin-Lu

2018-03-01

We aimed to determine the effect and mechanism of microRNA-21 (miR-21) on nerve cell regeneration and nerve functional recovery in diabetes mellitus combined with cerebral infarction (DM + CI) rats by targeting PDCD4. A total of 125 male Wistar rats were selected for DM + CI rat model construction and assigned into the blank, miR-21 mimics, mimics control, miR-21 inhibitor, inhibitor control, miR-21 inhibitor + si-PDCD4 and si-PDCD4 groups. And, 20 healthy rats were selected for the normal group. Triphenylterazolium chloride (TTC) staining and HE staining were used for determination of the area of CI and pathological changes, respectively. Behaviors of rats in the eight groups were determined by forelimb placement test and balance beam walking test. Immunohistochemical staining, double immunofluorescence staining assay, Western blotting, and qRT-PCR were used to detect expressions of miR-21, PDCD4, HNA, Nestin, NeuN, β-III-Tub, PTEN, FasL, and GFAP. DNA laddering and TUNEL staining was used for cell apoptosis. TTC and HE staining confirmed that 87.5% rats were induced into CI + DM models successfully. Results of forelimb placement test and balance beam walking test showed that miR-21 mimics, and si-PCDC4 improved the nerve defect of model rats. Comparing with the blank group at the same time, rats in the miR-21 inhibitor group displayed significant decrease in the forelimb placement test score, significant increase in the balance beam walking test score, and exacerbation of nerve defect, while rats in the miR-21 mimics and si-PCDC4 groups displayed significant increase in forelimb placement test score and significant decrease in the balance beam walking test score and improvement of nerve defect situation. The HNA, Nestin, and PDCD4 expressions were decreased and the NeuN, β-III-Tub, and GFAP expressions were increased in the miR-21 mimics and si-PDCD4 groups comparing with the blank group. The results of miR-21 inhibitor group were on the contrary. In comparison to the blank group, the miR-21 mimics group and the si-PDCD4 had lower miR-21 expressions and higher expressions of PDCD4, PTEN, and FasL, while the miR-21 inhibitor group was in the opposite trend. The results of qRT-PCR were the same with Western blotting. The expressions of fluorescence in other groups were higher than the normal group; compared with the blank group, the miR-21 mimics group and the si-PDCD4 group had lower fluorescence expression and DNA ladder. However, the fluorescence expressions and DNA ladder of miR-21 inhibitor group increased markedly in contrast with the blank group. Comparing with the blank group, BrdU + /DEX + fluorescence intensity significantly enhanced in the miR-21 mimics and si-PDCD4 groups and significantly reduced in the miR-21 inhibitor group. And, comparing with the blank group, in the miR-21 mimics group, the signal strength of luciferase carrying the wild-type PDCD4 was reduced by 25%. The present studies demonstrated that miR-21 could promote the nerve cell regeneration, suppress apoptosis of nerve cells in DM + CI rats and improves the nerve defect situation of DM + CI rats by inhibiting PDCD4.

Fluorescent discrimination between traces of chemical warfare agents and their mimics.

PubMed

Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

2014-03-19

An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

Characterization of rice lesion mimic mutants of 93-11 for a better understanding of general host defense response to both rice blast and sheath blight diseases

USDA-ARS?s Scientific Manuscript database

Rice lesion mimic mutants (LMM) exhibit necrotic lesions resembling programmed cell death (PCD). PCD is one of the significant hallmarks of disease resistance genes mediated defense responses. LMM can be used to study the mechanisms of plant disease resistance. In the present study, a total of 133 ...

Urinary bladder: normal appearance and mimics of malignancy at CT urography

PubMed Central

Sadow, Cheryl A.; Anik Sahni, V.; Silverman, Stuart G.

2011-01-01

Abstract The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists’ ability to diagnose bladder cancer. PMID:21771710

MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart.

PubMed

Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B; Angelos, Mark G; Khan, Mahmood

2015-03-01

: Cardiovascular disease is the number 1 cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure. Cell therapy (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA (miRNA) in the cardiac muscle and is downregulated in patients with MI. We hypothesized that reprogramming MSCs using miRNA mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs, and the levels of miR-133a were measured by quantitative real-time polymerase chain reaction. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic hearts. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels, and apoptosis-related genes (Apaf-1, Caspase-9, and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function, and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, quantitative real-time polymerase chain reaction data demonstrated a significant decrease in expression of the proapoptotic genes; Apaf-1, caspase-9, and caspase-3 in the miR-133a mimic transplanted group. Furthermore, luciferase reporter assay confirmed that miR-133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of patients undergoing stem cell transplantation for MI.

A bioartificial environment for kidney epithelial cells based on a supramolecular polymer basement membrane mimic and an organotypical culture system.

PubMed

Mollet, Björne B; Bogaerts, Iven L J; van Almen, Geert C; Dankers, Patricia Y W

2017-06-01

Renal applications in healthcare, such as renal replacement therapies and nephrotoxicity tests, could potentially benefit from bioartificial kidney membranes with fully differentiated and functional human tubular epithelial cells. A replacement of the natural environment of these cells is required to maintain and study cell functionality cell differentiation in vitro. Our approach was based on synthetic supramolecular biomaterials to mimic the natural basement membrane (BM) on which these cells grow and a bioreactor to provide the desired organotypical culture parameters. The BM mimics were constructed from ureidopyrimidinone (UPy)-functionalized polymer and bioactive peptides by electrospinning. The resultant membranes were shown to have a hierarchical fibrous BM-like structure consisting of self-assembled nanofibres within the electrospun microfibres. Human kidney-2 (HK-2) epithelial cells were cultured on the BM mimics under organotypical conditions in a custom-built bioreactor. The bioreactor facilitated in situ monitoring and functionality testing of the cultures. Cell viability and the integrity of the epithelial cell barrier were demonstrated inside the bioreactor by microscopy and transmembrane leakage of fluorescently labelled inulin, respectively. Furthermore, HK-2 cells maintained a polarized cell layer and showed modulation of both gene expression of membrane transporter proteins and metabolic activity of brush border enzymes when subjected to a continuous flow of culture medium inside the new bioreactor for 21 days. These results demonstrated that both the culture and study of renal epithelial cells was facilitated by the bioartificial in vitro environment that is formed by synthetic supramolecular BM mimics in our custom-built bioreactor. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Long non-coding RNA taurine-upregulated gene 1 predicts unfavorable prognosis, promotes cells proliferation, and inhibits cells apoptosis in epithelial ovarian cancer.

PubMed

Li, Tong-Huai; Zhang, Jing-Jing; Liu, Shao-Xiao; Chen, Yan

2018-05-01

The aim of this study was to evaluate the correlation of long non-coding RNAs (lncRNAs) taurine-upregulated gene 1 (TUG1) with clinicopathological characteristics as well as overall survival (OS) in epithelial ovarian cancer (EOC) patients, and investigate its function in EOC cells proliferation and apoptosis in vitro.LncRNA TUG1 expressions were detected in tumor tissues and paired adjacent tissues obtained from 96 EOC patients. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor plasmids were transfected into SKOV3 cells. CKK-8, annexin V-FITC-propidium iodide, qPCR and western blot assays were performed to detect cells proliferation, cells apoptosis, RNA expression, and protein expression, respectively.LncRNA TUG1 expression was higher in tumor tissue compared to paired adjacent tissue (P < .001), and it was positively correlated with pathological grade (P = .022), tumor size (P = .011) and FIGO stage (P < .001). Kaplan-Meier curve showed that lncRNA TUG1 high expression was associated with worse OS (P = .003). Multivariate Cox analysis indicated that lncRNA TUG1 high expression (vs. low expression) (P = .035) was independently predictive factor for shorter OS. In vitro, cells proliferation was promoted after treatment with lncRNA TUG1 mimic and was suppressed after treatment with lncRNA TUG1 inhibitor. In addition, cells apoptosis rate was decreased in lncRNA TUG1 mimic group compared to NC1 mimic, and increased in lncRNA TUG1 inhibitor group compared to NC2 inhibitor.In conclusion, lncRNA TUG1 is positively correlated with advanced disease and poor prognosis, and it promotes cells proliferation and inhibits cells apoptosis in EOC cells.

Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets.

PubMed

Wang, Xinhui; Yun, Jun-Won; Lei, Xin Gen

2014-01-10

Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1α pathway. Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular hydrogen peroxide (H2O2) and superoxide conditions for the present study to avoid confounding effects. Bioinformatics analyses of gene promoters and expression profiles guided the search for upstream signaling pathways to link the ebselen-initiated H2O2 scavenging to downstream key events of GSIS. The RNA interference was applied to prove PGC-1α as the main mediator for that link. Our study revealed a novel metabolic use and clinical potential of ebselen in rescuing GSIS in the GPX1-deficient islets and mice, along with distinct differences between the GPX and SOD mimics in this regard. These findings highlight the necessities and opportunities of discretional applications of various antioxidant enzyme mimics in treating insulin secretion disorders. REBOUND TRACK: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers: Regina Brigelius-Flohe, Vadim Gladyshev, Dexing Hou, and Holger Steinbrenner.

Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

PubMed

Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2017-06-25

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, synthesis, and characterization of a 39 amino acid peptide mimic of the main immunogenic region of the Torpedo acetylcholine receptor.

PubMed

Trinh, Vu B; Foster, Alex J; Fairclough, Robert H

2014-05-01

We have designed a 39 amino acid peptide mimic of the conformation-dependent main immunogenic region (MIR) of the Torpedo acetylcholine receptor (TAChR) that joins three discontinuous segments of the Torpedo α-subunit, α(1-12), α(65-79), and α(110 - 115) with two GS linkers: This 39MIR-mimic was expressed in E. coli as a fusion protein with an intein-chitin-binding domain (IChBD) to permit affinity collection on chitin beads. Six MIR-directed monoclonal antibodies (mAbs) bind to this complex and five agonist/antagonist site directed mAbs do not. The complex of MIR-directed mAb-132A with 39MIR has a Kd of (2.11±0.11)×10(-10)M, which is smaller than (7.13±1.20)×10(-10)M for the complex of mAb-132A with α(1-161) and about the same as 3.4×10(-10)M for that of mAb-132A with TAChR. Additionally, the 39MIR-IChBD adsorbs all MIR-directed antibodies (Abs) from an experimental autoimmune myasthenia gravis (EAMG) rat serum. Hence, the 39MIR-mimic has the potential to inactivate or remove pathogenic Torpedo MIR-directed Abs from EAMG sera and to direct a magic bullet to the memory B-cells that produce those pathogenic Abs. The hope is to use this as a guide to produce a mimic of the human MIR on the way to an antigen specific therapeutic agent to treat MG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Representing life in the Earth system with soil microbial functional traits in the MIMICS model

NASA Astrophysics Data System (ADS)

Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

2015-06-01

Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes, and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon (C) cycle-climate feedbacks. We used a microbial trait-based soil C model with two physiologically distinct microbial communities, and evaluate how this model represents soil C storage and response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model; these functional groups are akin to "gleaner" vs. "opportunist" plankton in the ocean, or r- vs. K-strategists in plant and animal communities. Here we compare MIMICS to a conventional soil C model, DAYCENT (the daily time-step version of the CENTURY model), in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that MIMICS projects much slower rates of soil C accumulation than a conventional soil biogeochemistry in response to increasing C inputs with elevated carbon dioxide (CO2) - a finding that would reduce the size of the land C sink estimated by the Earth system. Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

Histologic Mimics of Basal Cell Carcinoma.

PubMed

Stanoszek, Lauren M; Wang, Grace Y; Harms, Paul W

2017-11-01

- Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

Knockdown of Rice microRNA166 by Short Tandem Target Mimic (STTM).

PubMed

Teotia, Sachin; Zhang, Dabing; Tang, Guiliang

2017-01-01

Small RNAs, including microRNAs (miRNAs), are abundant in plants and play key roles in controlling plant development and physiology. miRNAs regulate the expression of the target genes involved in key plant processes. Due to functional redundancy among miRNA family members in plants, an ideal approach to silence the expression of all members simultaneously, for their functional characterization, is desirable. Target mimic (TM) was the first approach to achieve this goal. Short tandem target mimic (STTM) is a potent approach complementing TM for silencing miRNAs in plants. STTMs have been successfully used in dicots to block miRNA functions. Here, we describe in detail the protocol for designing STTM construct to block miRNA functions in rice. Such approach can be applied to silence miRNAs in other monocots as well.

Synthesis and Properties of the p-Sulfonamide Analogue of the Green Fluorescent Protein (GFP) Chromophore: The Mimic of GFP Chromophore with Very Strong N-H Photoacid Strength.

PubMed

Chen, Yi-Hui; Sung, Robert; Sung, Kuangsen

2018-04-06

The para-sulfonamide analogue ( p-TsABDI) of a green fluorescent protein (GFP) chromophore was synthesized to mimic the GFP chromophore. Its S 1 excited-state p K a * value in dimethylsulfoxide (DMSO) is -1.5, which is strong enough to partially protonate dipolar aprotic solvents and causes excited-state proton transfer (ESPT), so it can partially mimic the GFP chromophore to further study the ESPT-related photophysics and the blinking phenomenon of GFP. In comparison with 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) (p K a = 7.4, p K a * = 1.3 in water), p-TsABDI (p K a = 6.7, p K a * = -1.5 in DMSO) is a better photoacid for pH-jump studies.

Mimics and chameleons in motor neurone disease

PubMed Central

Turner, Martin R; Talbot, Kevin

2013-01-01

The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the ‘split hand’, head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life. PMID:23616620

Supradiaphragmatic ectopic liver: delayed traumatic hepatic hernia mimics pulmonary tumor.

PubMed

Huang, C-S; Hsu, W-H; Hsia, C-Y

2007-06-01

We present a rare case of a 63-year-old woman, the oldest one in the literature, with supradiaphragmatic ectopic liver that mimics a pulmonary nodule. The chest roentgenogram and chest computer tomography showed a lobulated tumor nearby the diaphragm. Pathological examination of the resected tumor disclosed only remarkable fatty liver change. Ectopic liver should be kept in mind to differentiate for the pulmonary tumor nearby the diaphragm.

Differential Item Functioning Detection Using the Multiple Indicators, Multiple Causes Method with a Pure Short Anchor

ERIC Educational Resources Information Center

Shih, Ching-Lin; Wang, Wen-Chung

2009-01-01

The multiple indicators, multiple causes (MIMIC) method with a pure short anchor was proposed to detect differential item functioning (DIF). A simulation study showed that the MIMIC method with an anchor of 1, 2, 4, or 10 DIF-free items yielded a well-controlled Type I error rate even when such tests contained as many as 40% DIF items. In general,…

The Role of SF2 in Prostate Cancer Progression

DTIC Science & Technology

2011-04-01

4 INTRODUCTION Background/Subject: Prostate cancer (PCa) is one of the most prevalent non-cutaneous cancers in men and the second...focused on the identification of PCa cell model systems and their subsequent manipulation of SF2 and cyclin D1 to mimic human disease (Subaim 1). The...Subaim 1: Generate PCa cells to mimic human disease. Summary: Preliminary data, in the initial Proposal, from a publically available gene expression

Three-dimensional printing (3DP) of neonatal head phantom for ultrasound: thermocouple embedding and simulation of bone.

PubMed

Gatto, Matteo; Memoli, Gianluca; Shaw, Adam; Sadhoo, Neelaksh; Gelat, Pierre; Harris, Russell A

2012-09-01

A neonatal head phantom, comprising of an ellipsoidal geometry and including a circular aperture for simulating the fontanel was designed and fabricated, in order to allow an objective assessment of thermal rise in tissues during trans-cranial ultrasonic scanning of pre-term neonates. The precise position of a series of thermocouples was determined on the basis of finite-element analysis, which identified crucial target points for the thermal monitoring within the phantom geometry. Three-Dimensional Printing (3DP) was employed for the manufacture of the skull phantom, which was subsequently filled with dedicated brain-mimic material. A novel 3DP material combination was found to be able to mimic the acoustic properties of neonatal skull bone. Similarly, variations of a standard recipe for tissue mimic were examined, until one was found to mimic the brain of an infant. A specific strategy was successfully pursued to embed a thermocouple within the 3DP skull phantom during the manufacturing process. An in-process machine vision system was used to assess the correct position of the deposited thermocouple inside the fabricated skull phantom. An external silicone-made skin-like covering completed the phantom and was manufactured through a Direct Rapid Tooling (DRT) technique. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death.

PubMed

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass ( Panicum virgatum ) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O -methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT -deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death

PubMed Central

Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

2017-01-01

Switchgrass (Panicum virgatum) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance. PMID:28676804

Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

PubMed

Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard

2017-08-01

To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

A peroxidase mimic with atom transfer radical polymerization activity constructed through the grafting of heme onto metal-organic frameworks.

PubMed

Jiang, Wei; Pan, Yue; Yang, Jiebing; Liu, Yong; Yang, Yan; Tang, Jun; Li, Quanshun

2018-07-01

Atom transfer radical polymerization (ATRP) has been considered to be an efficient strategy for constructing functional macromolecules owing to its simple operation and versatile monomers, and thus it is of great significance to develop ideal catalysts with higher activity and perfect reusability. We constructed a peroxidase mimic through the grafting of heme onto metal-organic frameworks UiO-66-NH 2 (ZrMOF), namely Heme-ZrMOF. After the systematic characterization of structure, the composite Heme-ZrMOF was demonstrated to possess high peroxidase activity using 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) and 3,3',5,5'-tetramethylbenzidine as substrates. The enzyme mimic was then used as catalysts in the ATRP reactions of different monomers, in which favorable monomer conversion (44.6-98.0%) and product molecular weight (8600-25,600 g/mol) could be obtained. Compared to free heme, Heme-ZrMOF could efficiently achieve the easy separation of heme from the catalytic system and facilitate the ATRP reaction in an aqueous environment to avoid the utilization of organic solvents. In conclusion, the enzyme mimic Heme-ZrMOF could be potentially used as an effective catalyst for preparing well-defined polymers with biomedical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center.

PubMed

Stevens, David A; Moss, Richard B; Hernandez, Cathy; Clemons, Karl V; Martinez, Marife

2016-04-01

Studies of cystic fibrosis (CF) patient exacerbations attributed toPseudomonas aeruginosainfection have indicated a lack of correlation of outcome within vitrosusceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum.Aspergillus fumigatusis the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillusdrug in this setting, and 30 CFAspergillusisolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences inAspergillussusceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The DNA-mimic antirestriction proteins ArdA ColIB-P9, Arn T4, and Ocr T7 as activators of H-NS-dependent gene transcription.

PubMed

Melkina, Olga E; Goryanin, Ignatiy I; Zavilgelsky, Gennadii B

2016-11-01

The antirestriction proteins ArdA ColIb-P9, Arn T4 and Ocr T7 specifically inhibit type I and type IV restriction enzymes and belong to the family of DNA-mimic proteins because their three-dimensional structure is similar to the double-helical B-form DNA. It is proposed that the DNA-mimic proteins are able to bind nucleoid protein H-NS and alleviate H-NS-silencing of the transcription of bacterial genes. Escherichia coli lux biosensors were constructed by inserting H-NS-dependent promoters into a vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE operon. It was demonstrated that the DNA-mimic proteins ArdA, Arn and Ocr activate the transcription of H-NS-dependent promoters of the lux operon of marine luminescent bacteria (mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio logei), and the dps gene from E. coli. It was also demonstrated that the ArdA antirestriction protein, the genes of which are located on transmissive plasmids ColIb-P9, R64, PK101, decreases levels of H-NS silencing of the PluxC promoter during conjugation in the recipient bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

PubMed Central

McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

2015-01-01

Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

Double Deception: Ant-Mimicking Spiders Elude Both Visually- and Chemically-Oriented Predators

PubMed Central

Uma, Divya; Durkee, Caitlin; Herzner, Gudrun; Weiss, Martha

2013-01-01

Biological mimicry is often multimodal, in that a mimic reinforces its resemblance to another organism via different kinds of signals that can be perceived by a specific target audience. In this paper we describe a novel scenario, in which a mimic deceives at least two distinct audiences, each of which relies primarily on a different sensory modality for decision-making. We have previously shown that Peckhamia picata, a myrmecomorphic spider that morphologically and behaviorally resembles the ant Camponotus nearcticus, experiences reduced predation by visually-oriented jumping spiders. Here we report that Peckhamia also faces reduced aggression from spider-hunting sphecid wasps as well as from its model ant, both of which use chemical cues to identify prey. We also report that Peckhamia does not chemically resemble its model ants, and that its total cuticular hydrocarbons are significantly lower than those of the ants and non-mimic spiders. Although further studies are needed to clarify the basis of Peckhamia's chemically-mediated protection, to our knowledge, such ‘double deception,’ in which a single organism sends misleading visual cues to one set of predators while chemically misleading another set, has not been reported; however, it is likely to be common among what have until now been considered purely visual mimics. PMID:24236152

Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center

PubMed Central

Moss, Richard B.; Hernandez, Cathy; Clemons, Karl V.; Martinez, Marife

2016-01-01

Studies of cystic fibrosis (CF) patient exacerbations attributed to Pseudomonas aeruginosa infection have indicated a lack of correlation of outcome with in vitro susceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum. Aspergillus fumigatus is the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillus drug in this setting, and 30 CF Aspergillus isolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences in Aspergillus susceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. PMID:26810647

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

PubMed Central

Rebouças, Júlio S.; Spasojević, Ivan

2010-01-01

Abstract Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia–reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO3·−, peroxyl radical, and less efficiently H2O2. By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and/or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877–918. PMID:20095865

Antifreeze Peptides and Glycopeptides, and Their Derivatives: Potential Uses in Biotechnology

PubMed Central

Bang, Jeong Kyu; Lee, Jun Hyuck; Murugan, Ravichandran N.; Lee, Sung Gu; Do, Hackwon; Koh, Hye Yeon; Shim, Hye-Eun; Kim, Hyun-Cheol; Kim, Hak Jun

2013-01-01

Antifreeze proteins (AFPs) and glycoproteins (AFGPs), collectively called AF(G)Ps, constitute a diverse class of proteins found in various Arctic and Antarctic fish, as well as in amphibians, plants, and insects. These compounds possess the ability to inhibit the formation of ice and are therefore essential to the survival of many marine teleost fishes that routinely encounter sub-zero temperatures. Owing to this property, AF(G)Ps have potential applications in many areas such as storage of cells or tissues at low temperature, ice slurries for refrigeration systems, and food storage. In contrast to AFGPs, which are composed of repeated tripeptide units (Ala-Ala-Thr)n with minor sequence variations, AFPs possess very different primary, secondary, and tertiary structures. The isolation and purification of AFGPs is laborious, costly, and often results in mixtures, making characterization difficult. Recent structural investigations into the mechanism by which linear and cyclic AFGPs inhibit ice crystallization have led to significant progress toward the synthesis and assessment of several synthetic mimics of AFGPs. This review article will summarize synthetic AFGP mimics as well as current challenges in designing compounds capable of mimicking AFGPs. It will also cover our recent efforts in exploring whether peptoid mimics can serve as structural and functional mimics of native AFGPs. PMID:23752356

An iron-iron hydrogenase mimic with appended electron reservoir for efficient proton reduction in aqueous media

PubMed Central

Becker, René; Amirjalayer, Saeed; Li, Ping; Woutersen, Sander; Reek, Joost N. H.

2016-01-01

The transition from a fossil-based economy to a hydrogen-based economy requires cheap and abundant, yet stable and efficient, hydrogen production catalysts. Nature shows the potential of iron-based catalysts such as the iron-iron hydrogenase (H2ase) enzyme, which catalyzes hydrogen evolution at rates similar to platinum with low overpotential. However, existing synthetic H2ase mimics generally suffer from low efficiency and oxygen sensitivity and generally operate in organic solvents. We report on a synthetic H2ase mimic that contains a redox-active phosphole ligand as an electron reservoir, a feature that is also crucial for the working of the natural enzyme. Using a combination of (spectro)electrochemistry and time-resolved infrared spectroscopy, we elucidate the unique redox behavior of the catalyst. We find that the electron reservoir actively partakes in the reduction of protons and that its electron-rich redox states are stabilized through ligand protonation. In dilute sulfuric acid, the catalyst has a turnover frequency of 7.0 × 104 s−1 at an overpotential of 0.66 V. This catalyst is tolerant to the presence of oxygen, thereby paving the way for a new generation of synthetic H2ase mimics that combine the benefits of the enzyme with synthetic versatility and improved stability. PMID:26844297

Leaf mimicry in a climbing plant protects against herbivory.

PubMed

Gianoli, Ernesto; Carrasco-Urra, Fernando

2014-05-05

Mimicry refers to adaptive similarity between a mimic organism and a model. Mimicry in animals is rather common, whereas documented cases in plants are rare, and the associated benefits are seldom elucidated [1, 2]. We show the occurrence of leaf mimicry in a climbing plant endemic to a temperate rainforest. The woody vine Boquila trifoliolata mimics the leaves of its supporting trees in terms of size, shape, color, orientation, petiole length, and/or tip spininess. Moreover, sequential leaf mimicry occurs when a single individual vine is associated with different tree species. Leaves of unsupported vines differed from leaves of climbing plants closely associated with tree foliage but did not differ from those of vines climbing onto leafless trunks. Consistent with an herbivory-avoidance hypothesis, leaf herbivory on unsupported vines was greater than that on vines climbing on trees but was greatest on vines climbing onto leafless trunks. Thus, B. trifoliolata gains protection against herbivory not merely by climbing and thus avoiding ground herbivores [3] but also by climbing onto trees whose leaves are mimicked. Unlike earlier cases of plant mimicry or crypsis, in which the plant roughly resembles a background or color pattern [4-7] or mimics a single host [8, 9], B. trifoliolata is able to mimic several hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Marijuana and chocolate.

PubMed

James, J S

1996-10-18

Three substances in chocolate and cocoa powder may mimic cannabinoid by activating receptors or increasing anandamide levels. Anandamide is a lipid that binds to cannabinoid receptors and mimics the psychoactive effects of the drug. Chocolate is widely believed to enhance the effect of marijuana. A practical implication of this finding is that the amount of marijuana needed for medicinal purposes may be decreased by using it with chocolate, reducing both the risks and cost associated with marijuana.

Hormone Replacement Therapy, Iron, and Breast Cancer

DTIC Science & Technology

2004-11-01

accumulates due to the mutation of the HFE gene (hemochromatosis EeJ, iron elevated in the mouse body mimics the post-menopausal condition. In the present...model. Since iron slowly accumulates due to the mutation of the HFE gene (hemochromatosis Fe), iron elevated in the mouse body mimics the post...menopausal condition. Development of iron overloaded transgenic mice: The murine HFE gene is structurally similar to the human gene . Four different HFE gene

Lewis Y Antigen as a Target for Breast Cancer Therapy

DTIC Science & Technology

1997-09-01

YYRYD GroupC Polysaccharide (x(2-9)sialic acid that is highlv functional both in vitro and in vivo. We showed in vivo protective immune responses in...group C meningococcal polysaccharide (MCP) (35). We have recently reported that peptides containing aromatic motifs (Table 1) can effectively mimic...characterization of a monoclonal antibody produced in response to a group-C Meningococcal polysaccharide peptide mimic. Molecular Immunology 1996;33:503-510. 20

Lewis Y Antigen as a Target for Breast Cancer Therapy

DTIC Science & Technology

1996-09-01

have shown that a synthetic peptide can mimic the capsular polysaccharide of N. meningitis serogroup C (MCP) in that it induces an anti-MCP immune...intervening residue. All these sequences resemble the peptide we have identified as a mimic of the group C meningococcal polysaccharide . The immunological...Group C Polysaccharide ct(2-9)sialic acid The sequence similarities among the putative motifs suggest that antibodies raised to this peptide set might

Cannabinoid mimics in chocolate utilized as an argument in court.

PubMed

Tytgat, J; Van Boven, M; Daenens, P

2000-01-01

A case is presented involving chocolate cannabinoid mimics which have been utilized in court by the defendant's lawyer in order to clear the accused of smoking and dealing in marijuana after he was found positive for cannabis in a routine urine immunoassay screening test. The argumentation in this case was that the accused had supposedly eaten a massive amount of chocolate which contained anandamide-related lipids. These lipids inhibit anandamide hydrolysis in the brain, act as cannabinoid mimics and, according to the lawyer, were the cause of the positive cannabinoid test. To investigate this in detail, we synthesized N-oleoyl- and N-linoleoylethanolamide and spiked these compounds together with N-arachidonoylethanolamide in urine for immunological investigations. None of the samples were found positive, indicating that no cross-reactivity occurs with cannabinoids. As a result, the lawyer's claim could be refuted and the accused was convicted.

Effects of Muslims praying (Salat) on EEG gamma activity.

PubMed

Doufesh, Hazem; Ibrahim, Fatimah; Safari, Mohammad

2016-08-01

This study investigates the difference of mean gamma EEG power between actual and mimic Salat practices in twenty healthy Muslim subjects. In the actual Salat practice, the participants were asked to recite and performing the physical steps in all four stages of Salat; whereas in the mimic Salat practice, they were instructed to perform only the physical steps without recitation. The gamma power during actual Salat was statistically higher than during mimic Salat in the frontal and parietal regions in all stages. In the actual Salat practice, the left hemisphere exhibited significantly higher mean gamma power in all cerebral regions and all stages, except the central-parietal region in the sitting position, and the frontal area in the bowing position. Increased gamma power during Salat, possibly related to an increase in cognitive and attentional processing, supports the concept of Salat as a focus attention meditation. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Multifunctional, supramolecular, continuous artificial nacre fibres

NASA Astrophysics Data System (ADS)

Hu, Xiaozhen; Xu, Zhen; Gao, Chao

2012-10-01

Nature has created amazing materials during the process of evolution, inspiring scientists to studiously mimic them. Nacre is of particular interest, and it has been studied for more than half-century for its strong, stiff, and tough attributes resulting from the recognized ``brick-and-mortar'' (B&M) layered structure comprised of inorganic aragonite platelets and biomacromolecules. The past two decades have witnessed great advances in nacre-mimetic composites, but they are solely limited in films with finite size (centimetre-scale). To realize the adream target of continuous nacre-mimics with perfect structures is still a great challenge unresolved. Here, we present a simple and scalable strategy to produce bio-mimic continuous fibres with B&M structures of alternating graphene sheets and hyperbranched polyglycerol (HPG) binders via wet-spinning assembly technology. The resulting macroscopic supramolecular fibres exhibit excellent mechanical properties comparable or even superior to nacre and bone, and possess fine electrical conductivity and outstanding corrosion-resistance.

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

Thanos, Loukas; Galani, Panagiota, E-mail: paga@hol.gr; Mylona, Sophia

The purpose of this study was to determine the diagnostic value of percutaneous core needle biopsy (CNB) relative to fine needle aspiration (FNA) in patients with pneumonia and pneumonia mimics. In this prospective study we present our experience with 48 thoracic FNAs and CNBs carried out on 48 patients with pneumonia and pneumonia mimics. Samples were obtained from all patients using both CNB (with an automated 18-G core biopsy needle and a gun) and FNA (with a 22-G needle). A specific diagnosis was made in 10/48 cases (20.83%) by FNA and in 42/48 (87.5%) by CNB. The main complications encounteredmore » were pneumothorax (n = 4) and hemoptysis (n = 2), yielding a total complication rate of 12.5%. We concluded that CNB using an automated biopsy gun results in a higher diagnostic accuracy for pneumonia and pneumonia mimic biopsies than FNA. Complications should be considered and proper patient observation should follow the procedure.« less

Necrotizing fasciitis and its mimics: what radiologists need to know.

PubMed

Chaudhry, Ammar A; Baker, Kevin S; Gould, Elaine S; Gupta, Rajarsi

2015-01-01

The purpose of this article is to review the imaging features of necrotizing fasciitis and its potential mimics. Key imaging features are emphasized to enable accurate and efficient interpretation of variables that are essential in appropriate management. Necrotizing fasciitis is a medical emergency with potential lethal outcome. Dissecting gas along fascial planes in the absence of penetrating trauma (including iatrogenic) is essentially pathognomonic. However, the lack of soft-tissue emphysema does not exclude the diagnosis. Mimics of necrotizing fasciitis include nonnecrotizing fasciitis (eosinophilic, paraneoplastic, inflammatory (lupus myofasciitis, Churg-Strauss, nodular, or proliferative), myositis, neoplasm, myonecrosis, inflammatory myopathy, and compartment syndrome. Necrotizing fasciitis is a clinical diagnosis, and imaging can reveal nonspecific or negative findings (particularly during the early course of disease). One should be familiar with salient clinical and imaging findings of necrotizing fasciitis to facilitate a more rapid and accurate diagnosis and be aware that its diagnosis necessitates immediate discussion with the referring physician.

Sensitive fluorescence on-off probes for the fast detection of a chemical warfare agent mimic.

PubMed

Khan, Muhammad Shar Jhahan; Wang, Ya-Wen; Senge, Mathias O; Peng, Yu

2018-01-15

Two highly sensitive probes bearing a nucleophilic imine moiety have been utilized for the selective detection of chemical warfare agent (CWA) mimics. Diethyl chlorophosphate (DCP) was used as mimic CWAs. Both iminocoumarin-benzothiazole-based probes not only demonstrated a remarkable fluorescence ON-OFF response and good recognition, but also exhibited fast response times (10s) along with color changes upon addition of DCP. Limits of detection for the two sensors 1 and 2 were calculated as 0.065μM and 0.21μM, respectively, which are much lower than most other reported probes. These two probes not only show high sensitivity and selectivity in solution, but can also be applied for the recognition of DCP in the gas state, with significant color changes easily observed by the naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of a new series of ebselen derivatives as glutathione peroxidase (GPx) mimics and cholinesterase inhibitors against Alzheimer's disease.

PubMed

Luo, Zonghua; Liang, Liang; Sheng, Jianfei; Pang, Yanqing; Li, Jianheng; Huang, Ling; Li, Xingshu

2014-02-15

A series of ebselen derivatives were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and glutathione peroxidase (GPx) mimics. Most of the compounds were found to be potent against AChEs and BuChE, compounds 5e and 5i, proved to be the most potent against AChE with IC₅₀ values of 0.76 and 0.46 μM, respectively. Among these hybrids, most of the compounds were found to be good GPx mimics compare with ebselen. The selected compounds 5e and 5i were also used to determine the catalytic parameters and in vitro hydrogen peroxide scavenging activity. The results indicate that compounds 5e and 5i may be excellent multifunctional agents for the treatment of AD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA

NASA Astrophysics Data System (ADS)

Ziach, Krzysztof; Chollet, Céline; Parissi, Vincent; Prabhakaran, Panchami; Marchivie, Mathieu; Corvaglia, Valentina; Bose, Partha Pratim; Laxmi-Reddy, Katta; Godde, Frédéric; Schmitter, Jean-Marie; Chaignepain, Stéphane; Pourquier, Philippe; Huc, Ivan

2018-05-01

Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. These molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer-protein interactions, whereas sequence-selective enzymes were not inhibited. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein-DNA interactions.

Phenol degradation catalyzed by a peroxidase mimic constructed through the grafting of heme onto metal-organic frameworks.

PubMed

Jiang, Wei; Yang, Jiebing; Wang, Xinghuo; Han, Haobo; Yang, Yan; Tang, Jun; Li, Quanshun

2018-01-01

The aim of this work was to construct a peroxidase mimic for achieving the phenol degradation through Fenton reaction. The enzyme mimic was synthesized through the conjugation of heme with the amino group of 2-amino-1,4-benzene dicarboxylate in UiO-66-NH 2 (ZrMOF), namely Heme-ZrMOF. Compared to free heme, the composite Heme-ZrMOF exhibited an obviously enhanced ability for phenol degradation with up to 97.3% of phenol removal after 2h. Meanwhile, it could achieve the easy separation of catalyst from the system and the elimination of iron residues in the process of phenol degradation. Finally, the catalyst Heme-ZrMOF was observed to possess good recyclability in the phenol degradation with still 76.2% of phenol removal after 4 cycles. Copyright © 2017 Elsevier Ltd. All rights reserved.

Natural Products and Their Mimics as Targets of Opportunity for Discovery

PubMed Central

2017-01-01

Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding. PMID:28738152

An allosteric photoredox catalyst inspired by photosynthetic machinery

PubMed Central

Lifschitz, Alejo M.; Young, Ryan M.; Mendez-Arroyo, Jose; Stern, Charlotte L.; McGuirk, C. Michael; Wasielewski, Michael R.; Mirkin, Chad A.

2015-01-01

Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices. PMID:25817586

A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes

NASA Astrophysics Data System (ADS)

Wang, Meng; Lin, Bao-Ping; Yang, Hong

2016-12-01

In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices.

A plant tendril mimic soft actuator with phototunable bending and chiral twisting motion modes.

PubMed

Wang, Meng; Lin, Bao-Ping; Yang, Hong

2016-12-22

In nature, plant tendrils can produce two fundamental motion modes, bending and chiral twisting (helical curling) distortions, under the stimuli of sunlight, humidity, wetting or other atmospheric conditions. To date, many artificial plant-like mechanical machines have been developed. Although some previously reported materials could realize bending or chiral twisting through tailoring the samples into various ribbons along different orientations, each single ribbon could execute only one deformation mode. The challenging task is how to endow one individual plant tendril mimic material with two different, fully tunable and reversible motion modes (bending and chiral twisting). Here we show a dual-layer, dual-composition polysiloxane-based liquid crystal soft actuator strategy to synthesize a plant tendril mimic material capable of performing two different three-dimensional reversible transformations (bending versus chiral twisting) through modulation of the wavelength band of light stimuli (ultraviolet versus near-infrared). This material has broad application prospects in biomimetic control devices.

Why does Kevlar decompose, while Nomex does not, when treated with aqueous chlorine solutions?

PubMed

Akdag, Akin; Kocer, Hasan B; Worley, S D; Broughton, R M; Webb, T R; Bray, Travis H

2007-05-24

Kevlar and Nomex are high-performance polymers which have wide varieties of applications in daily life. Recently, they have been proposed to be biocidal materials when reacted with household bleach (sodium hypochlorite solution) because they contain amide moieties which can be chlorinated to generate biocidal N-halamine functional groups. Although Nomex can be chlorinated without any significant decomposition, Kevlar decomposes under the same chlorination conditions. In this study, two mimics for each of the polymers were synthesized to simulate the carboxylate and diaminophenylene components of the materials. It was found that the p-diaminophenylene component of the Kevlar mimic is oxidized to a quinone-type structure upon treatment with hypochlorous acid, which then decomposes. However, such a mechanism for the Nomex mimic is not possible. In this paper, based upon these observations, a plausible answer will be provided to the title question.

Combined experimental and theoretical study on the reactivity of compounds I and II in horseradish peroxidase biomimetics.

PubMed

Ji, Li; Franke, Alicja; Brindell, Małgorzata; Oszajca, Maria; Zahl, Achim; van Eldik, Rudi

2014-10-27

For the exploration of the intrinsic reactivity of two key active species in the catalytic cycle of horseradish peroxidase (HRP), Compound I (HRP-I) and Compound II (HRP-II), we generated in situ [Fe(IV) O(TMP(+.) )(2-MeIm)](+) and [Fe(IV) O(TMP)(2-MeIm)](0) (TMP=5,10,15,20-tetramesitylporphyrin; 2-MeIm=2-methylimidazole) as biomimetics for HRP-I and HRP-II, respectively. Their catalytic activities in epoxidation, hydrogen abstraction, and heteroatom oxidation reactions were studied in acetonitrile at -15 °C by utilizing rapid-scan UV/Vis spectroscopy. Comparison of the second-order rate constants measured for the direct reactions of the HRP-I and HRP-II mimics with the selected substrates clearly confirmed the outstanding oxidizing capability of the HRP-I mimic, which is significantly higher than that of HRP-II. The experimental study was supported by computational modeling (DFT calculations) of the oxidation mechanism of the selected substrates with the involvement of quartet and doublet HRP-I mimics ((2,4) Cpd I) and the closed-shell triplet spin HRP-II model ((3) Cpd II) as oxidizing species. The significantly lower activation barriers calculated for the oxidation systems involving (2,4) Cpd I than those found for (3) Cpd II are in line with the much higher oxidizing efficiency of the HRP-I mimic proven in the experimental part of the study. In addition, the DFT calculations show that all three reaction types catalyzed by HRP-I occur on the doublet spin surface in an effectively concerted manner, whereas these reactions may proceed in a stepwise mechanism with the HRP-II mimic as oxidant. However, the high desaturation or oxygen rebound barriers during CH bond activation processes by the HRP-II mimic predict a sufficient lifetime for the substrate radical formed through hydrogen abstraction. Thus, the theoretical calculations suggest that the dissociation of the substrate radical may be a more favorable pathway than desaturation or oxygen rebound processes. Importantly, depending on the electronic nature of the oxidizing species, that is, (2,4) Cpd I or (3) Cpd II, an interesting region-selective conversion phenomenon between sulfoxidation and H-atom abstraction was revealed in the course of the oxidation reaction of dimethylsulfide. The combined experimental and theoretical study on the elucidation of the intrinsic reactivity patterns of the HRP-I and HRP-II mimics provides a valuable tool for evaluating the particular role of the HRP active species in biological systems. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A synthetic mimic of protein inner space: buried polar interactions in a deep water-soluble host.

PubMed

Butterfield, Sara M; Rebek, Julius

2006-12-06

A deep water-soluble cavitand was functionalized with a carboxylic acid directed toward the hydrophobic interior of the host. The buried salt-bridge interaction formed with a quinuclidium cationic guest was determined to be worth -3 kcal/mol using a free energy cycle. The strength of the interaction correlates well with buried salt bridges in proteins, indicating that the cavitand interior mimics the hydrophobic inner space of proteins.

Clinical Mimics: An Emergency Medicine Focused Review of Anxiety Mimics: Journal of Emergency Medicine

DTIC Science & Technology

2017-12-09

acutely agitated or moderately anxious patient, therapies that possess quick onset of action are the most useful. Benzodiazepines are the recommended...lorazepam 0.50mg or diazepam and midazolam in 1-2 mg increments.7 These medications should be used for acute treatment in the ED, with few pills provided...http://www.epilepsy.com/ learn/types-epilepsy- syndromes /temporal-lobe-epilepsy 13. Johns Hopkins Medicine. Myasthenia Gravis. Available from: http

A practical review of the muscles of facial mimicry with special emphasis on the superficial musculoaponeurotic system.

PubMed

Hutto, Justin R; Vattoth, Surjith

2015-01-01

In this article, we elaborate a practical approach to superficial facial anatomy enabling easy identification of the facial mimic muscles by classifying them according to their shared common insertion sites. The facial mimic muscles are often difficult to identify on imaging. By tracing them from their common group insertion sites back to their individual origins as well as understanding key anatomic relationships, radiologists can more accurately identify these muscles.

Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

DTIC Science & Technology

2014-05-01

in May 2013, the difference between nude mice (which lack T- cells , but still have a partially functional adaptive and innate immune system) and NSG...Mangada J, Greiner DL, Handgretinger R. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human...Targeting of Cerebral Breast Cancer Metastases Using a T- Cell Receptor Mimic Antibody PRINCIPAL INVESTIGATOR: Ulrich Bickel

Structural Mimics of the [Fe]-Hydrogenase: A Complete Set for Group VIII Metals.

PubMed

Barik, Chandan Kr; Ganguly, Rakesh; Li, Yongxin; Leong, Weng Kee

2018-06-18

A set of structural mimics of the [Fe]-hydrogenase active site comprising all the group VIII metals, viz., [M(2-NHC(O)C 5 H 4 N)(CO) 2 (2-S-C 5 H 4 N)], has been synthesized. They exist as a mixture of isomers in solution, and the relative stability of the isomers depends on the nature of the metal and the substituent at the 6-position of the pyridine ligand.

Recognition of extended linear and cyclised polyketide mimics by a type II acyl carrier protein† †Electronic supplementary information (ESI) available: Detailed experimental procedures and characterisation data for all new compounds, additional spectra and structural statistics for derivatised ACP three-dimensional structures. See DOI: 10.1039/c5sc03864b Click here for additional data file.

PubMed Central

Dong, Xu; Bailey, Christopher D.; Williams, Christopher; Crosby, John; Simpson, Thomas J.

2016-01-01

Polyketides are secondary metabolites which display both valuable pharmaceutical and agrochemical properties. Biosynthesis is performed by polyketide synthases (PKSs), and the acyl carrier protein (ACP), a small acidic protein, that transports the growing polyketide chain and is essential for activity. Here we report the synthesis of two aromatic probes and a linear octaketide mimic that have been tethered to actinorhodin ACP. These experiments were aimed at probing the ACP's capacity to sequester a non-polar versus a phenolic aromatic ring (that more closely mimics a polyketide intermediate) as well as investigations with extended polyketide chain surrogates. The binding of these mimics has been assessed using high-resolution solution NMR studies and high-resolution structure determination. These results reveal that surprisingly a PKS ACP is able to bind and sequester a bulky non-polar substrate containing an aromatic ring in a fatty acid type binding mode, but the introduction of even a small degree of polarity favours a markedly different association at a surface site that is distinct from that employed by fatty acid ACPs. PMID:28936328

Antibacterial Peptidomimetics: Polymeric Synthetic Mimics of Antimicrobial Peptides

NASA Astrophysics Data System (ADS)

Lienkamp, Karen; Madkour, Ahmad E.; Tew, Gregory N.

Polymer-based peptidomimetics, or proteinomimetics, are a relatively young and dynamic field of research. The ability to successfully mimic the biochemical activity of antimicrobial peptides (AMPs) has been demonstrated by several groups. This has been accomplished by careful tuning of the molecule's hydrophobicity and charge density. At the same time, many important questions remain to be answered, including the role of backbone rigidity, details of membrane insertion, and the role of curvature in the self-assemblies between these novel peptidemimetics and phospholipids. As the biological properties of polymeric synthetic mimics of AMPs (SMAMPs) result from the interplay of many parameters, it is not yet possible to predict the exact properties of such molecules from their mere chemical structure. However, as demonstrated here, the effect of certain design features such as charge and hydrophobicity on the properties across a polymer series is understood. Compared to the mechanistic specifics that are known about the interactions of AMPs or small antibacterial molecules with membranes and cells, relatively little is known concerning the interaction of polymeric SMAMPs with membranes. Beyond SMAMPs, numerous opportunities exist and protein transduction domain mimics are an active area of research in the Tew laboratory. These two examples, one quite new and the other studied for almost a decade, demonstrate that it is possible to teach synthetic polymers to behave like peptides, despite their lack of sequence specificity and secondary structure.

Quantification of therapeutic miRNA mimics in whole blood from nonhuman primates.

PubMed

Kelnar, Kevin; Peltier, Heidi J; Leatherbury, Neil; Stoudemire, Jay; Bader, Andreas G

2014-02-04

MRX34, a microRNA (miRNA)-based therapy for cancer, has recently entered clinical trials as the first clinical candidate in its class. It is a liposomal nanoparticle loaded with a synthetic mimic of the tumor suppressor miRNA miR-34a as the active pharmaceutical ingredient. To understand the pharmacokinetic properties of the drug and to rationalize an optimal dosing regimen in the clinic, a method is needed to quantitatively detect the miRNA mimic. Here, we report the development and qualification of a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay in support of pharmacokinetic and toxicokinetic assessments in the nonhuman primate. Detection and quantification were performed on total ribonucleic acid (RNA) isolated from whole blood. The qualified range of the standard curve spans 6 orders of magnitude from 2.5 × 10(-7) to 2.5 × 10(-1) ng per reverse transcription (RT) reaction, corresponding to an estimated blood concentration from 6.2 × 10(-5) to 6.2 × 10(1) ng/mL. Our results demonstrate that endogenous as well as the exogenous miR-34a can be accurately and precisely quantified. The assay was used to establish the pharmacokinetic profile of MRX34, showing a favorable residence time and exposure of the miRNA mimic in whole blood from nonhuman primates.

Fast and Efficient Drosophila melanogaster Gene Knock-Ins Using MiMIC Transposons

PubMed Central

Vilain, Sven; Vanhauwaert, Roeland; Maes, Ine; Schoovaerts, Nils; Zhou, Lujia; Soukup, Sandra; da Cunha, Raquel; Lauwers, Elsa; Fiers, Mark; Verstreken, Patrik

2014-01-01

Modern molecular genetics studies necessitate the manipulation of genes in their endogenous locus, but most of the current methodologies require an inefficient donor-dependent homologous recombination step to locally modify the genome. Here we describe a methodology to efficiently generate Drosophila knock-in alleles by capitalizing on the availability of numerous genomic MiMIC transposon insertions carrying recombinogenic attP sites. Our methodology entails the efficient PhiC31-mediated integration of a recombination cassette flanked by unique I-SceI and/or I-CreI restriction enzyme sites into an attP-site. These restriction enzyme sites allow for double-strand break−mediated removal of unwanted flanking transposon sequences, while leaving the desired genomic modifications or recombination cassettes. As a proof-of-principle, we mutated LRRK, tau, and sky by using different MiMIC elements. We replaced 6 kb of genomic DNA encompassing the tau locus and 35 kb encompassing the sky locus with a recombination cassette that permits easy integration of DNA at these loci and we also generated a functional LRRKHA knock in allele. Given that ~92% of the Drosophila genes are located within the vicinity (<35 kb) of a MiMIC element, our methodology enables the efficient manipulation of nearly every locus in the fruit fly genome without the need for inefficient donor-dependent homologous recombination events. PMID:25298537

Fast and efficient Drosophila melanogaster gene knock-ins using MiMIC transposons.

PubMed

Vilain, Sven; Vanhauwaert, Roeland; Maes, Ine; Schoovaerts, Nils; Zhou, Lujia; Soukup, Sandra; da Cunha, Raquel; Lauwers, Elsa; Fiers, Mark; Verstreken, Patrik

2014-10-08

Modern molecular genetics studies necessitate the manipulation of genes in their endogenous locus, but most of the current methodologies require an inefficient donor-dependent homologous recombination step to locally modify the genome. Here we describe a methodology to efficiently generate Drosophila knock-in alleles by capitalizing on the availability of numerous genomic MiMIC transposon insertions carrying recombinogenic attP sites. Our methodology entails the efficient PhiC31-mediated integration of a recombination cassette flanked by unique I-SceI and/or I-CreI restriction enzyme sites into an attP-site. These restriction enzyme sites allow for double-strand break-mediated removal of unwanted flanking transposon sequences, while leaving the desired genomic modifications or recombination cassettes. As a proof-of-principle, we mutated LRRK, tau, and sky by using different MiMIC elements. We replaced 6 kb of genomic DNA encompassing the tau locus and 35 kb encompassing the sky locus with a recombination cassette that permits easy integration of DNA at these loci and we also generated a functional LRRK(HA) knock in allele. Given that ~92% of the Drosophila genes are located within the vicinity (<35 kb) of a MiMIC element, our methodology enables the efficient manipulation of nearly every locus in the fruit fly genome without the need for inefficient donor-dependent homologous recombination events. Copyright © 2014 Vilain et al.

Sensitive electrochemical assaying of DNA methyltransferase activity based on mimic-hybridization chain reaction amplified strategy.

PubMed

Zhang, Linqun; Liu, Yuanjian; Li, Ying; Zhao, Yuewu; Wei, Wei; Liu, Songqin

2016-08-24

A mimic-hybridization chain reaction (mimic-HCR) amplified strategy was proposed for sensitive electrochemically detection of DNA methylation and methyltransferase (MTase) activity In the presence of methylated DNA, DNA-gold nanoparticles (DNA-AuNPs) were captured on the electrode by sandwich-type assembly. It then triggered mimic-HCR of two hairpin probes to produce many long double-helix chains for numerous hexaammineruthenium (III) chloride ([Ru(NH3)6](3+), RuHex) inserting. As a result, the signal for electrochemically detection of DNA MTase activity could be amplified. If DNA was non-methylated, however, the sandwich-type assembly would not form because the short double-stranded DNAs (dsDNA) on the Au electrode could be cleaved and digested by restriction endonuclease HpaII (HapII) and exonuclease III (Exo III), resulting in the signal decrement. Based on this, an electrochemical approach for detection of M.SssI MTase activity with high sensitivity was developed. The linear range for M.SssI MTase activity was from 0.05 U mL(-1) to 10 U mL(-1), with a detection limit down to 0.03 U mL(-1). Moreover, this detecting strategy held great promise as an easy-to-use and highly sensitive method for other MTase activity and inhibition detection by exchanging the corresponding DNA sequence. Copyright © 2016 Elsevier B.V. All rights reserved.

Neisseria conserved protein DMP19 is a DNA mimic protein that prevents DNA binding to a hypothetical nitrogen-response transcription factor

PubMed Central

Wang, Hao-Ching; Ko, Tzu-Ping; Wu, Mao-Lun; Ku, Shan-Chi; Wu, Hsing-Ju; Wang, Andrew H.-J.

2012-01-01

DNA mimic proteins occupy the DNA binding sites of DNA-binding proteins, and prevent these sites from being accessed by DNA. We show here that the Neisseria conserved hypothetical protein DMP19 acts as a DNA mimic. The crystal structure of DMP19 shows a dsDNA-like negative charge distribution on the surface, suggesting that this protein should be added to the short list of known DNA mimic proteins. The crystal structure of another related protein, NHTF (Neisseria hypothetical transcription factor), provides evidence that it is a member of the xenobiotic-response element (XRE) family of transcriptional factors. NHTF binds to a palindromic DNA sequence containing a 5′-TGTNAN11TNACA-3′ recognition box that controls the expression of an NHTF-related operon in which the conserved nitrogen-response protein [i.e. (Protein-PII) uridylyltransferase] is encoded. The complementary surface charges between DMP19 and NHTF suggest specific charge–charge interaction. In a DNA-binding assay, we found that DMP19 can prevent NHTF from binding to its DNA-binding sites. Finally, we used an in situ gene regulation assay to provide evidence that NHTF is a repressor of its down-stream genes and that DMP19 can neutralize this effect. We therefore conclude that the interaction of DMP19 and NHTF provides a novel gene regulation mechanism in Neisseria spps. PMID:22373915

A Collection of Target Mimics for Comprehensive Analysis of MicroRNA Function in Arabidopsis thaliana

PubMed Central

Paz-Ares, Javier; Weigel, Detlef

2010-01-01

Many targets of plant microRNAs (miRNAs) are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for ∼20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA–resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants. PMID:20661442

Multimodal confocal mosaics enable high sensitivity and specificity in screening of in situ squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Grados Luyando, Maria del Carmen; Bar, Anna; Snavely, Nicholas; Jacques, Steven; Gareau, Daniel S.

2014-02-01

Screening cancer in excision margins with confocal microscopy may potentially save time and cost over the gold standard histopathology (H and E). However, diagnostic accuracy requires sufficient contrast and resolution to reveal pathological traits in a growing set of tumor types. Reflectance mode images structural details due to microscopic refractive index variation. Nuclear contrast with acridine orange fluorescence provides enhanced diagnostic value, but fails for in situ squamous cell carcinoma (SCC), where the cytoplasm is important to visualize. Combination of three modes [eosin (Eo) fluorescence, reflectance (R) and acridine orange (AO) fluorescence] enable imaging of cytoplasm, collagen and nuclei respectively. Toward rapid intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaics can image wide surgical margins (~1cm) with sub-cellular resolution and mimic the appearance of conventional H and E. Absorption contrast is achieved by alternating the excitation wavelength: 488nm (AO fluorescence) and 532nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H and E, enabling detection of the carcinoma in situ in the epidermal layer The sum mosaic Eo+R is false-colored pink to mimic eosins' appearance in H and E, while the AO mosaic is false-colored purple to mimic hematoxylins' appearance in H and E. In this study, mosaics of 10 Mohs surgical excisions containing SCC in situ and 5 containing only normal tissue were subdivided for digital presentation equivalent to 4X histology. Of the total 16 SCC in situ multimodal mosaics and 16 normal cases presented, two reviewers made 1 and 2 (respectively) type-2 errors (false positives) but otherwise scored perfectly when using the confocal images to screen for the presence of SCC in situ as compared to the gold standard histopathology. Limitations to precisely mimic H and E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues.

Characterization and fine mapping of a light-dependent leaf lesion mimic mutant 1 in rice.

PubMed

Wang, Jing; Ye, Bangquan; Yin, Junjie; Yuan, Can; Zhou, Xiaogang; Li, Weitao; He, Min; Wang, Jichun; Chen, Weilan; Qin, Peng; Ma, Bintian; Wang, Yuping; Li, Shigui; Chen, Xuewei

2015-12-01

Plants that spontaneously produce lesion mimics or spots, without any signs of obvious adversity, such as pesticide and mechanical damage, or pathogen infection, are so-called lesion mimic mutants (lmms). In rice, many lmms exhibit enhanced resistance to pathogens, which provides a unique opportunity to uncover the molecular mechanism underlying lmms. We isolated a rice light-dependent leaf lesion mimic mutant 1 (llm1). Lesion spots appeared in the leaves of the llm1 mutant at the tillering stage. Furthermore, the mutant llm1 had similar agronomic traits to wild type rice. Trypan blue and diamiobenzidine staining analyses revealed that the lesion spot formation on the llm1 mutant was due to programmed cell death and reactive oxygen species. The chloroplasts were severely damaged in the llm1 mutant, suggesting that chloroplast damage was associated with the formation of lesion spots in llm1. More importantly, llm1 exhibited enhanced resistance to bacterial blight pathogens within increased expression of pathogenesis related genes (PRs). Using a map-based cloning approach, we delimited the LLM1 locus to a 121-kb interval between two simple sequence repeat markers, RM17470 and RM17473, on chromosome 4. We sequenced the candidate genes on the interval and found that a base mutation had substituted adenine phosphate for thymine in the last exon of LOC_Os04g52130, which led to an amino acid change (Asp(388) to Val) in the llm1 mutant. Our investigation showed that the putative coproporphyrinogen III oxidase (CPOX) encoded by LOC_Os04g52130 was produced by LLM1 and that amino acid Asp(388) was essential for CPOX function. Our study provides the basis for further investigations into the mechanism underlying lesion mimic initiation associated with LLM1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Antibacterial TAP-mimic electrospun polymer scaffold: effects on P. gingivalis-infected dentin biofilm.

PubMed

Albuquerque, Maria Tereza P; Evans, Joshua D; Gregory, Richard L; Valera, Marcia C; Bottino, Marco C

2016-03-01

This study sought to investigate, in vitro, the effects of a recently developed triple antibiotic paste (TAP)-mimic polymer nanofibrous scaffold against Porphyromonas gingivalis-infected dentin biofilm. Dentin specimens (4 × 4 × 1 mm(3)) were prepared from human canines. The specimens were sterilized, inoculated with P. gingivalis (ATCC 33277), and incubated for 1 week to allow for biofilm formation. Infected dentin specimens were exposed for 3 days to the following treatments: antibiotic-free polydioxanone scaffold (PDS, control), PDS + 25 wt% TAP [25 mg of each antibiotic (metronidazole, ciprofloxacin, and minocycline) per mL of the PDS polymer solution], or a saturated TAP-based solution (50 mg of each antibiotic per mL of saline solution). In order to serve as the negative control, infected dentin specimens were left untreated (bacteria only). To determine the antimicrobial efficacy of the TAP-mimic scaffold, a colony-forming unit (CFU) per milliliter (n = 10/group) measurement was performed. Furthermore, additional specimens (n = 2/group) were prepared to qualitatively study biofilm inhibition via scanning electron microscopy (SEM). Statistics were performed, and significance was set at the 5% level. Both the TAP-mimic scaffold and the positive control (TAP solution) led to complete bacterial elimination, differing statistically (p < 0.05) from the negative control group (bacteria only). No statistical differences were observed for CFU per milliliter data between antibiotic-free scaffolds (2.7 log10 CFU/mL) and the negative control (5.9 log10 CFU/mL). The obtained data revealed significant antimicrobial properties of the novel PDS-based TAP-mimic scaffold against an established P. gingivalis-infected dentin biofilm. Collectively, the data suggest that the proposed nanofibrous scaffold might be used as an alternative to the advocated clinical gold standard (i.e., TAP) for intracanal disinfection prior to regenerative endodontics.

Manganese superoxide dismutase, MnSOD and its mimics.

PubMed

Miriyala, Sumitra; Spasojevic, Ivan; Tovmasyan, Artak; Salvemini, Daniela; Vujaskovic, Zeljko; St Clair, Daret; Batinic-Haberle, Ines

2012-05-01

Increased understanding of the role of mitochondria under physiological and pathological conditions parallels increased exploration of synthetic and natural compounds able to mimic MnSOD - endogenous mitochondrial antioxidant defense essential for the existence of virtually all aerobic organisms from bacteria to humans. This review describes most successful mitochondrially-targeted redox-active compounds, Mn porphyrins and MitoQ(10) in detail, and briefly addresses several other compounds that are either catalysts of O(2)(-) dismutation, or its non-catalytic scavengers, and that reportedly attenuate mitochondrial dysfunction. While not a true catalyst (SOD mimic) of O(2)(-) dismutation, MitoQ(10) oxidizes O(2)(-) to O(2) with a high rate constant. In vivo it is readily reduced to quinol, MitoQH(2), which in turn reduces ONOO(-) to NO(2), producing semiquinone radical that subsequently dismutes to MitoQ(10) and MitoQH(2), completing the "catalytic" cycle. In MitoQ(10), the redox-active unit was coupled via 10-carbon atom alkyl chain to monocationic triphenylphosphonium ion in order to reach the mitochondria. Mn porphyrin-based SOD mimics, however, were designed so that their multiple cationic charge and alkyl chains determine both their remarkable SOD potency and carry them into the mitochondria. Several animal efficacy studies such as skin carcinogenesis and UVB-mediated mtDNA damage, and subcellular distribution studies of Saccharomyces cerevisiae and mouse heart provided unambiguous evidence that Mn porphyrins mimic the site and action of MnSOD, which in turn contributes to their efficacy in numerous in vitro and in vivo models of oxidative stress. Within a class of Mn porphyrins, lipophilic analogs are particularly effective for treating central nervous system injuries where mitochondria play key role. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Resembling a viper: implications of mimicry for conservation of the endangered smooth snake.

PubMed

Valkonen, Janne K; Mappes, Johanna

2014-12-01

The phenomenon of Batesian mimicry, where a palatable animal gains protection against predation by resembling an unpalatable model, has been a core interest of evolutionary biologists for 150 years. An extensive range of studies has focused on revealing mechanistic aspects of mimicry (shared education and generalization of predators) and the evolutionary dynamics of mimicry systems (co-operation vs. conflict) and revealed that protective mimicry is widespread and is important for individual fitness. However, according to our knowledge, there are no case studies where mimicry theories have been applied to conservation of mimetic species. Theoretically, mimicry affects, for example, frequency dependency of predator avoidance learning and human induced mortality. We examined the case of the protected, endangered, nonvenomous smooth snake (Coronella austriaca) that mimics the nonprotected venomous adder (Vipera berus), both of which occur in the Åland archipelago, Finland. To quantify the added predation risk on smooth snakes caused by the rarity of vipers, we calculated risk estimates from experimental data. Resemblance of vipers enhances survival of smooth snakes against bird predation because many predators avoid touching venomous vipers. Mimetic resemblance is however disadvantageous against human predators, who kill venomous vipers and accidentally kill endangered, protected smooth snakes. We found that the effective population size of the adders in Åland is very low relative to its smooth snake mimic (28.93 and 41.35, respectively).Because Batesian mimicry is advantageous for the mimic only if model species exist in sufficiently high numbers, it is likely that the conservation program for smooth snakes will fail if adders continue to be destroyed. Understanding the population consequences of mimetic species may be crucial to the success of endangered species conservation. We suggest that when a Batesian mimic requires protection, conservation planners should not ignore the model species (or co-mimic in Mullerian mimicry rings) even if it is not itself endangered. © 2014 Society for Conservation Biology.

Finding the Stable Structures of N1-xWx with an Ab Initio High-Throughput Approach

DTIC Science & Technology

2015-05-26

W. These include borides , carbides, oxides, and other nitrides. We also invented many structures to mimic the random pattern of vacancies on both the...structures. These include nitrides, oxides, borides , and carbides, as well as supercells of standard structures with atoms removed to mimic the random patter...1930). [15] R. Kiessling and Y. H. Liu, Thermal stability of the chromium, iron, and tungsten borides in streaming ammonia and the existence of a new

A Comprehensive Structural Analysis Process for Failure Assessment in Aircraft Lap-Joint Mimics Using Multi-Modal Fusion of NDE Data (Preprint)

DTIC Science & Technology

2012-07-01

plates with dimensions of 254 mm (10") by 76.2 mm (3") with a nominal thickness of 1.6 mm (0.063’’). Two aluminum plates were stacked and riveted to...create a lap-joint mimic test panel. Thus, ten aluminum plates produced five test panels. Prior to stacking and riveting , the aluminum plates of the... riveted region of the panels. 5 Approved for public release; distribution unlimited. Figure 1

MIMIC-compatible GaAs and InP field effect controlled transferred electron (FECTED) oscillators

NASA Astrophysics Data System (ADS)

Scheiber, Helmut; Luebke, Kurt; Diskus, Christian G.; Thim, Hartwig W.; Gruetzmacher, D.

1989-12-01

A MIMIC-(millimeter and microwave integrated circuit) compatible transferred electron oscillator is investigated which utilizes the frequency-independent negative resistance of the stationary charge dipole domain that forms in the channel of a MESFET. The device structure, analysis, and simulation are described. Devices fabricated from GaAs and InP exhibit very high power levels of 56 mW at 29 GHz and 55 mW at 34 GHz, respectively. Continuous wave power levels are somewhat lower (30 mW).

MOCVD Process Technology for Affordable, High-Yield, High-Performance MESFET Structures. MIMIC Phase 3

DTIC Science & Technology

1993-01-26

by an optical pyrometer that views the inside of the susceptor through a sapphire light pipe. The gas delivery system is of standard commercial design ...of the operating conditions for MESFET growth. 2.2.2 Modifications to the Apparatus for MIMIC Spire designed and installed a bell jar capable of...withstanding, without water cooling, the 500 to 1 100’C temperatures needed for MOCVD growth. The bell jar features a flow disrupter of proprietary design

Affinity selection of Nipah and Hendra virus-related vaccine candidates from a complex random peptide library displayed on bacteriophage virus-like particles

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

Peabody, David S.; Chackerian, Bryce; Ashley, Carlee

The invention relates to virus-like particles of bacteriophage MS2 (MS2 VLPs) displaying peptide epitopes or peptide mimics of epitopes of Nipah Virus envelope glycoprotein that elicit an immune response against Nipah Virus upon vaccination of humans or animals. Affinity selection on Nipah Virus-neutralizing monoclonal antibodies using random sequence peptide libraries on MS2 VLPs selected peptides with sequence similarity to peptide sequences found within the envelope glycoprotein of Nipah itself, thus identifying the epitopes the antibodies recognize. The selected peptide sequences themselves are not necessarily identical in all respects to a sequence within Nipah Virus glycoprotein, and therefore may be referredmore » to as epitope mimics VLPs displaying these epitope mimics can serve as vaccine. On the other hand, display of the corresponding wild-type sequence derived from Nipah Virus and corresponding to the epitope mapped by affinity selection, may also be used as a vaccine.« less

The sociomicrobiology of antivirulence drug resistance: a proof of concept.

PubMed

Mellbye, Brett; Schuster, Martin

2011-01-01

Antivirulence drugs disarm rather than kill pathogens and are thought to alleviate the problem of resistance, although there is no evidence to support this notion. Quorum sensing (QS) often controls cooperative virulence factor production and is therefore an attractive antivirulence target, for which inhibitors (QSI) have been developed. We designed a proof-of-principle experiment to investigate the impact of bacterial social interactions on the evolution of QSI resistance. We cocultured Pseudomonas aeruginosa QS-deficient mutants with small proportions of the QS-proficient wild type, which in the absence of QSI mimic QSI-sensitive and -resistant variants, respectively. We employed two different QS-dependent nutrients that are degraded by extracellular (public) and cell-associated (private) enzymes. QS mutants (QSI-sensitive mimics) behaved as social cheaters that delayed population growth and prevented enrichment of wild-type cooperators (QSI-resistant mimics) only when nutrient acquisition was public, suggesting that QSI resistance would not spread. This highlights the potential for antivirulence strategies that target cooperative behaviors and provides a conceptual framework for future studies.

Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state.

PubMed

Zhang, Yingyue; Algburi, Ammar; Wang, Ning; Kholodovych, Vladyslav; Oh, Drym O; Chikindas, Michael; Uhrich, Kathryn E

2017-02-01

Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low μg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens. Copyright © 2016 Elsevier Inc. All rights reserved.

Recent Advances in the Development of Chromophore-Based Chemosensors for Nerve Agents and Phosgene.

PubMed

Chen, Liyan; Wu, Di; Yoon, Juyoung

2018-01-26

The extreme toxicity and ready accessibility of nerve agents and phosgene has caused an increase in the demand to develop effective systems for the detection of these substances. Among the traditional platforms utilized for this purpose, chemosensors including surface acoustic wave (SAW) sensors, enzymes, carbon nanotubes, nanoparticles, and chromophore based sensors have attracted increasing attention. In this review, we describe in a comprehensive manner recent progress that has been made on the development of chromophore-based chemosensors for detecting nerve agents (mimic) and phosgene. This review comprises two sections focusing on studies of the development of chemosensors for nerve agents (mimic) and phosgene. In each of the sections, the discussion follows a format which concentrates on different reaction sites/mechanisms involved in the sensing processes. Finally, chemosensors uncovered in these efforts are compared with those based on other sensing methods and challenges facing the design of more effective chemosensors for the detection of nerve agents (mimic) and phosgene are discussed.

Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness.

PubMed

Xie, Ying; Wehrkamp, Cody J; Li, Jing; Wang, Yan; Wang, Yazhe; Mott, Justin L; Oupický, David

2016-03-07

Cholangiocarcinoma is the second most common primary liver malignancy with extremely poor prognosis due to early invasion and widespread metastasis. The invasion and metastasis are regulated by multiple factors including CXCR4 chemokine receptor and multiple microRNAs. The goal of this study was to test the hypothesis that inhibition of CXCR4 combined with the action of miR-200c mimic will cooperatively enhance the inhibition of the invasion of human cholangiocarcinoma cells. The results show that CXCR4-inhibition polycation PCX can effectively deliver miR-200c mimic and that the combination treatment consisting of PCX and miR-200c results in cooperative antimigration activity, most likely by coupling the CXCR4 axis blockade with epithelial-to-mesenchymal transition inhibition in the cholangiocarcinoma cells. The ability of the combined PCX/miR-200c treatment to obstruct two migratory pathways represents a promising antimetastatic strategy in cholangiocarcinoma.

Synthesis, physicochemical characterization and biological evaluation of chitosan sulfate as heparan sulfate mimics.

PubMed

Doncel-Pérez, Ernesto; Aranaz, Inmaculada; Bastida, Agatha; Revuelta, Julia; Camacho, Celia; Acosta, Niuris; Garrido, Leoncio; Civera, Concepción; García-Junceda, Eduardo; Heras, Angeles; Fernández-Mayoralas, Alfonso

2018-07-01

Despite the relevant biological functions of heparan sulfate (HS) glycosaminoglycans, their limited availability and the chemical heterogeneity from natural sources hamper their use for biomedical applications. Chitosan sulfates (ChS) exhibit structural similarity to HSs and may mimic their biological functions. We prepared a variety of ChS with different degree of sulfation to evaluate their ability to mimic HS in protein binding and to promote neural cell division and differentiation. The structure of the products was characterized using various spectroscopic and analytical methods. The study of their interaction with different growth factors showed that ChS bound to the proteins similarly or even better than heparin. In cell cultures, a transition effect on cell number was observed as a function of ChS concentration. Differences in promoting the expression of the differentiation markers were also found depending on the degree of sulfation and modification in the chitosan. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased NIH 3T3 fibroblast functions on cell culture dishes which mimic the nanometer fibers of natural tissues.

PubMed

Bhardwaj, Garima; Webster, Thomas J

2015-01-01

Traditional flat tissue cell culture dishes have consisted of polystyrene treated with plasma gases for growing, subculturing, and studying cell behavior in vitro. However, increasingly it has been observed that mimicking natural tissue properties (such as chemistry, three-dimensional structure, mechanical properties, etc) in vitro can lead to a better correlation of in vitro to in vivo cellular functions. The following studies compared traditional NIH 3T3 fibroblasts' functions on XanoMatrix scaffolds to standard tissue culture polystyrene. Results found significantly greater fibroblast adhesion and proliferation on XanoMatrix cell culture dishes which mimic the nanoscale geometry of natural tissue fibers with true, tortuous fiber beds creating a robust, consistent, and versatile growth platform. In this manner, this study supports that cell culture dishes which mimic features of natural tissues should be continually studied for a wide range of applications in which mimicking natural cellular functions are important.

Engineering hydrogels as extracellular matrix mimics

PubMed Central

Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun

2010-01-01

Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine. PMID:20394538

Comparative effectiveness of a clinostat and a slow-turning lateral vessel at mimicking the ultrastructural effects of microgravity in plant cells

NASA Technical Reports Server (NTRS)

Moore, R.

1990-01-01

The object of this research was to determine how effectively the actions of a clinostat and a fluid-filled, slow-turning lateral vessel (STLV) mimic the ultrastructural effects of microgravity in plant cells. We accomplished this by qualitatively and quantitatively comparing the ultrastructures of cells grown on clinostats and in an STLV with those of cells grown at 1 g and in microgravity aboard the Space Shuttle Columbia. Columella cells of Brassica perviridis seedlings grown in microgravity and in an STLV have similar structures. Both contain significantly more lipid bodies, less starch, and fewer dictyosomes than columella cells of seedlings grown at 1 g. Cells of seedlings grown on clinostats have significantly different ultrastructures from those grown in microgravity or in an STLV, indicating that clinostats do not mimic microgravity at the ultrastructural level. The similar structures of columella cells of seedlings grown in an STLV and in microgravity suggest that an STLV effectively mimics microgravity at the ultrastructural level.

Synthesis of diethylamino-curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells.

PubMed

Ahn, Yongchel; Oh, Sangtae; Lee, Seong Jun; Park, Byong-Gon; Park, Yoon-Sun; Shin, Woon-Seob; Jang, Hyuk Jai; Park, Jin Hoon; Kwon, Daeho; Lee, Seokjoon

2014-08-01

A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.

An Enzyme-Free Signal Amplification Technique for Ultrasensitive Colorimetric Assay of Disease Biomarkers

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

Ye, Haihang; Yang, Kuikun; Tao, Jing

Enzyme-based colorimetric assays have been widely used in research labs and clinical diagnosis for decades. Nevertheless, as constrained by the performance of enzymes, their detection sensitivity has not been substantially improved in recent years, which inhibits many critical applications such as early detection of cancers. In this work, we demonstrate an enzyme-free signal amplification technique, based on gold vesicles encapsulated with Pd-Ir nanoparticles as peroxidase mimics, for colorimetric assay of disease biomarkers with significantly enhanced sensitivity. This technique overcomes the intrinsic limitations of enzymes, thanks to the superior catalytic efficiency of peroxidase mimics and the efficient loading and release ofmore » these mimics. Using human prostate surface antigen as a model biomarker, we demonstrated that the enzyme-free assay could reach a limit of detection at the femtogram/mL level, which is over 10 3-fold lower than that of conventional enzyme-based assay when the same antibodies and similar procedure were used.« less

An allosteric photoredox catalyst inspired by photosynthetic machinery

DOE PAGES

Lifschitz, Alejo M.; Young, Ryan M.; Mendez-Arroyo, Jose; ...

2015-03-30

Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switchingmore » using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Furthermore, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.« less

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

PubMed

Schwalbe, E C; Hicks, D; Rafiee, G; Bashton, M; Gohlke, H; Enshaei, A; Potluri, S; Matthiesen, J; Mather, M; Taleongpong, P; Chaston, R; Silmon, A; Curtis, A; Lindsey, J C; Crosier, S; Smith, A J; Goschzik, T; Doz, F; Rutkowski, S; Lannering, B; Pietsch, T; Bailey, S; Williamson, D; Clifford, S C

2017-10-18

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

An Enzyme-Free Signal Amplification Technique for Ultrasensitive Colorimetric Assay of Disease Biomarkers

DOE PAGES

Ye, Haihang; Yang, Kuikun; Tao, Jing; ...

2017-01-30

Enzyme-based colorimetric assays have been widely used in research labs and clinical diagnosis for decades. Nevertheless, as constrained by the performance of enzymes, their detection sensitivity has not been substantially improved in recent years, which inhibits many critical applications such as early detection of cancers. In this work, we demonstrate an enzyme-free signal amplification technique, based on gold vesicles encapsulated with Pd-Ir nanoparticles as peroxidase mimics, for colorimetric assay of disease biomarkers with significantly enhanced sensitivity. This technique overcomes the intrinsic limitations of enzymes, thanks to the superior catalytic efficiency of peroxidase mimics and the efficient loading and release ofmore » these mimics. Using human prostate surface antigen as a model biomarker, we demonstrated that the enzyme-free assay could reach a limit of detection at the femtogram/mL level, which is over 10 3-fold lower than that of conventional enzyme-based assay when the same antibodies and similar procedure were used.« less

Biomaterials for 4D stem cell culture

PubMed Central

Hilderbrand, Amber M.; Ovadia, Elisa M.; Rehmann, Matthew S.; Kharkar, Prathamesh M.; Guo, Chen; Kloxin, April M.

2017-01-01

Stem cells reside in complex three-dimensional (3D) environments within the body that change with time, promoting various cellular functions and processes such as migration and differentiation. These complex changes in the surrounding environment dictate cell fate yet, until recently, have been challenging to mimic within cell culture systems. Hydrogel-based biomaterials are well suited to mimic aspects of these in vivo environments, owing to their high water content, soft tissue-like elasticity, and often-tunable biochemical content. Further, hydrogels can be engineered to achieve changes in matrix properties over time to better mimic dynamic native microenvironments for probing and directing stem cell function and fate. This review will focus on techniques to form hydrogel-based biomaterials and modify their properties in time during cell culture using select addition reactions, cleavage reactions, or non-covalent interactions. Recent applications of these techniques for the culture of stem cells in four dimensions (i.e., in three dimensions with changes over time) also will be discussed for studying essential stem cell processes. PMID:28717344

Membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers: selectivity against model bacterial and mammalian membranes.

PubMed

Wang, Ying; Tang, Yanli; Zhou, Zhijun; Ji, Eunkyung; Lopez, Gabriel P; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

2010-08-03

Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and cationic phenylene ethynylene oligomers (OPEs) exhibit broad-spectrum antimicrobial activity, and their main target is believed to be the cell membrane. To understand better how these antimicrobial molecules interact with membranes, a series of PPE-based CPEs and OPEs with different side chains were studied. Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes were used as model membranes. Among the CPEs and OPEs tested, the anionic CPE, PPE-SO(3)(2-) and the smallest cationic OPE-1 are inactive against all vesicles. Other cationic CPEs and OPEs show significant membrane perturbation ability against bacterial membrane mimics but are inactive against a mammalian cell membrane mimic with the exception of PPE-DABCO and two end-only-functionalized OPEs, which also disrupted a mammalian cell membrane mimic. The results suggest that the phospholipid composition of vesicles dominates the interaction of CPE and OPE with lipid membranes.

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.

The Face of the Chameleon: The Experience of Facial Mimicry for the Mimicker and the Mimickee

PubMed Central

Kulesza, Wojciech Marek; Cisłak, Aleksandra; Vallacher, Robin R.; Nowak, Andrzej; Czekiel, Martyna; Bedynska, Sylwia

2015-01-01

ABSTRACT This research addressed three questions concerning facial mimicry: (a) Does the relationship between mimicry and liking characterize all facial expressions, or is it limited to specific expressions? (b) Is the relationship between facial mimicry and liking symmetrical for the mimicker and the mimickee? (c) Does conscious mimicry have consequences for emotion recognition? A paradigm is introduced in which participants interact over a computer setup with a confederate whose prerecorded facial displays of emotion are synchronized with participants’ behavior to create the illusion of social interaction. In Experiment 1, the confederate did or did not mimic participants’ facial displays of various subsets of basic emotions. Mimicry promoted greater liking for the confederate regardless of which emotions were mimicked. Experiment 2 reversed these roles: participants were instructed to mimic or not to mimic the confederate’s facial displays. Mimicry did not affect liking for the confederate but it did impair emotion recognition. PMID:25811746

Synthesis and high-throughput processing of polymeric hydrogels for 3D cell culture.

PubMed

Lowe, Stuart B; Tan, Vincent T G; Soeriyadi, Alexander H; Davis, Thomas P; Gooding, J Justin

2014-09-17

3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.

Molecular and ionic mimicry and the transport of toxic metals

PubMed Central

Bridges, Christy C.; Zalups, Rudolfs K.

2008-01-01

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues. PMID:15845419

Infectious Disease: Connecting Innate Immunity to Biocidal Polymers

PubMed Central

Gabriel, Gregory J.; Som, Abhigyan; Madkour, Ahmad E.; Eren, Tarik; Tew, Gregory N.

2007-01-01

Infectious disease is a critically important global healthcare issue. In the U.S. alone there are 2 million new cases of hospital-acquired infections annually leading to 90,000 deaths and 5 billion dollars of added healthcare costs. Couple these numbers with the appearance of new antibiotic resistant bacterial strains and the increasing occurrences of community-type outbreaks, and clearly this is an important problem. Our review attempts to bridge the research areas of natural host defense peptides (HDPs), a component of the innate immune system, and biocidal cationic polymers. Recently discovered peptidomimetics and other synthetic mimics of HDPs, that can be short oligomers as well as polymeric macromolecules, provide a unique link between these two areas. An emerging class of these mimics are the facially amphiphilic polymers that aim to emulate the physicochemical properties of HDPs but take advantage of the synthetic ease of polymers. These mimics have been designed with antimicrobial activity and, importantly, selectivity that rivals natural HDPs. In addition to providing some perspective on HDPs, selective mimics, and biocidal polymers, focus is given to the arsenal of biophysical techniques available to study their mode of action and interactions with phospholipid membranes. The issue of lipid type is highlighted and the important role of negative curvature lipids is illustrated. Finally, materials applications (for instance, in the development of permanently antibacterial surfaces) are discussed as this is an important part of controlling the spread of infectious disease. PMID:18160969

Skin lesions over the pocket area that may mimic cardiac implantable electronic device infection: A case series.

PubMed

Korantzopoulos, Panagiotis; Plakoutsi, Sofia; Florou, Elizabeth; Bechlioulis, Aris

2018-05-21

The early and correct diagnosis of cardiac implantable electronic device (CIED) infections is critical given that early aggressive treatment with complete removal of the system along with antimicrobial therapy dramatically improves outcomes. Pocket infection manifested by local signs of inflammation is the most common form of CIED infections. Conditions mimicking pocket infection have been described in the literature. These include various types of malignancy and rarely allergic reactions/contact dermatitis to pacemaker compounds. We aimed to describe skin lesions and disorders over the pocket area that mimic CIED infection. We present a series of 5 cases with skin lesions that mimic pocket infection. We document these cases with corresponding photographs. Most of them have not been described in this setting. We report the following cases of conditions that proved not to be CIED infection: One case of superficial cellulitis, one case of herpes zoster over the pocket area, one case of spontaneous bruising over the pocket a long time after implantation in a patient taking oral anticoagulation, and 2 cases of contact dermatitis due to prolonged postoperative application of povidone iodine. All cases had favorable outcome after conservative treatment and no CIED infection was developed during follow-up. Clinicians should be aware of rare conditions that mimic CIED infection. Incorrect diagnosis of these disorders may falsely lead to CIED extraction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The MIMIC Code Repository: enabling reproducibility in critical care research.

PubMed

Johnson, Alistair Ew; Stone, David J; Celi, Leo A; Pollard, Tom J

2018-01-01

Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset. Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies. Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository's issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource. The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible. By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Antioxidant activity of selenenamide-based mimic as a function of the aromatic thiols nucleophilicity, a DFT-SAPE model.

PubMed

Kheirabadi, Ramesh; Izadyar, Mohammad

2018-05-18

The mechanism of action of the selenenamide 1 as a mimic of the glutathione peroxidase (GPx) was investigated by the density functional theory. The solvent-assisted proton exchange procedure was applied to model the catalytic behavior and antioxidant activity of this mimic. To have an insight into the charge transfer effect, different aromatic thiols, including electron donating substituents on the phenyl ring were considered. The catalytic behavior of the selenenamide was modeled in a four-step mechanism, described by the oxidation of the mimic, the reduction of the obtained product, selenoxide, the reduction of the selenenylsulfide and dehydration of selenenic acid. On the basis of the activation parameters, the final step of the proposed mechanism is the rate determining states of the catalytic cycle. Turnover frequency (TOF) analysis showed that the electron donating groups at the para-position of the phenyl ring of the PhSH do not affect the catalytic activity of the selenenamide in contrast to p-methyl thiophenol which indicates the highest nucleophilicity. The evaluation of the electronic contribution of the various donating groups on the phenyl ring of the aromatic thiols shows that the antioxidant activity of the selenenamide sufficiently increases in the presence of the electron-donating substitutions. Finally, the charge transfer process at the rate-determining state was investigated based on the natural bond orbital analysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular and ionic mimicry and the transport of toxic metals

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

Bridges, Christy C.; Zalups, Rudolfs K.

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport ofmore » selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.« less

How and what do autistic children see? Emotional, perceptive and social peculiarities reflected in more recent examinations of the visual perception and the process of observation in autistic children.

PubMed

Dalferth, M

1989-01-01

Autistic symptoms become apparent at the earliest during the 2nd-3rd month of life when the spontaneous registration of the meaning of specific-visual stimuli (eyes, configuration of the mother's face) do not occur and also learning experiences by reason of mimic and gestures repeatedly shown by the interaction partner can neither evoke a social smile nor stimulate anticipational behaviour. Even with increasing age an empathetic perception of feelings in the corresponding mimical gesticular formation is very difficult and they themselves are only insufficiently able to express their own feelings intelligibly to everyone. As mimic and gestures are, however, visually perceived, the autistic perceptive child's competence is of great importance. On the basis of the examinations of visual perception (retinal pathology, tunnel vision) perceptual processing (recognition of feelings, sex and age) and the disintegration of multimodal stimuli it can be presumed that social and emotional deficits are to be seen in connection with a deviant perceptive interpretation of the world and irregular processing on the basis of a neuro-biological handicap (the absence of a genetic determined reference-system for emotionally significant stimuli), which can have various causes (comp. Gillberg 1988) and also impede the adequate expression of feelings in mimic, gestures and voice. Autistic people see, experience and understand the world in a specific way in which and by which they differ from non-handicapped people.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterizing Strokes and Stroke Mimics Transported by Helicopter Emergency Medical Services.

PubMed

Sequeira, Denisse; Martin-Gill, Christian; Kesinger, Matthew R; Thompson, Laura R; Jovin, Tudor G; Massaro, Lori M; Guyette, Francis X

2016-01-01

Stroke is the leading cause of disability in the United States with most of these patients being transported by emergency medical services. These providers are the first medical point of contact and must be able to rapidly and accurately identify stroke and transport these patients to the appropriate facilities for treatment. There are many conditions that have similar presentations to stroke and can be mistakenly identified as potential strokes, thereby affecting the initial prehospital triage. A retrospective observational study examined patients with suspected strokes transported to a single comprehensive stroke center (CSC) by a helicopter emergency medical service (HEMS) agency from 2007 through 2013. Final diagnosis was extracted from the Get with the Guidelines (GWTG) database and hospital discharge diagnosis for those not included in the database. Frequencies of discharge diagnosis were calculated and then stratified into interfacility vs. scene transfers. In this study 6,243 patients were transported: 3,376 patients were screened as potential strokes, of which 2,527 had a final diagnosis of stroke (2,242 ischemic stroke and 285 transient ischemic attack), 166 had intracranial hemorrhage, and 655 were stroke mimics. Stroke mimics were more common among scene transfers (223, 32%) than among interfacility transfers (432, 16%). In our study approximately 20% of potential stroke patients transported via HEMS were mimics. Identifying the need for CSC resources can be an important factor in creating a prehospital triage tool to facilitate patient transport to an appropriate health care facility.

Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2.

PubMed

McCune, Broc T; Tang, Wei; Lu, Jia; Eaglesham, James B; Thorne, Lucy; Mayer, Anne E; Condiff, Emily; Nice, Timothy J; Goodfellow, Ian; Krezel, Andrzej M; Virgin, Herbert W

2017-07-11

The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail. VAPA was required for the efficiency of a step(s) in the viral replication cycle after entry of viral RNA into the cytoplasm but before the synthesis of viral minus-sense RNA. The interaction of VAPA with viral NS1/2 proteins is conserved between murine and human noroviruses. Murine norovirus NS1/2 directly bound the major sperm protein (MSP) domain of VAPA through its NS1 domain. Mutations within NS1 that disrupted interaction with VAPA inhibited viral replication. Structural analysis revealed that the viral NS1 domain contains a mimic of the phenylalanine-phenylalanine-acidic-tract (FFAT) motif that enables host proteins to bind to the VAPA MSP domain. The NS1/2-FFAT mimic region interacted with the VAPA-MSP domain in a manner similar to that seen with bona fide host FFAT motifs. Amino acids in the FFAT mimic region of the NS1 domain that are important for viral replication are highly conserved across murine norovirus strains. Thus, VAPA interaction with a norovirus protein that functionally mimics host FFAT motifs is important for murine norovirus replication. IMPORTANCE Human noroviruses are a leading cause of gastroenteritis worldwide, but host factors involved in norovirus replication are incompletely understood. Murine noroviruses have been studied to define mechanisms of norovirus replication. Here we defined the importance of the interaction between the hitherto poorly studied NS1/2 norovirus protein and the VAPA host protein. The NS1/2-VAPA interaction is conserved between murine and human noroviruses and was important for early steps in murine norovirus replication. Using structure-function analysis, we found that NS1/2 contains a short sequence that molecularly mimics the FFAT motif that is found in multiple host proteins that bind VAPA. This represents to our knowledge the first example of functionally important mimicry of a host FFAT motif by a microbial protein. Copyright © 2017 McCune et al.

An investigation into anti-proliferative effects of microRNAs encoded by the miR-106a-363 cluster on human carcinoma cells and keratinocytes using microarray profiling of miRNA transcriptomes

PubMed Central

Khuu, Cuong; Jevnaker, Anne-Marthe; Bryne, Magne; Osmundsen, Harald

2014-01-01

Transfection of human oral squamous carcinoma cells (clone E10) with mimics for unexpressed miR-20b or miR-363-5p, encoded by the miR-106a-363 cluster (miR-20b, miR-106a, miR-363-3p, or miR-363-5p), caused 40–50% decrease in proliferation. Transfection with mimics for miR-18a or miR-92a, encoded by the miR-17-92 cluster (all members being expressed in E10 cells), had no effect on proliferation. In contrast, mimic for the sibling miRNA-19a yielded about 20% inhibition of proliferation. To investigate miRNA involvement profiling of miRNA transcriptomes were carried out using deoxyoligonucleotide microarrays. In transfectants for miR-19a, or miR-20b or miR-363-5p most differentially expressed miRNAs exhibited decreased expression, including some miRNAs encoded in paralogous miR-17-92—or miR-106b-25 cluster. Only in cells transfected with miR-19a mimic significantly increased expression of miR-20b observed—about 50-fold as judged by qRT-PCR. Further studies using qRT-PCR showed that transfection of E10 cells with mimic for miRNAs encoded by miR-17-92 - or miR-106a-363 - or the miR-106b-25 cluster confirmed selective effect on expression on sibling miRNAs. We conclude that high levels of miRNAs encoded by the miR-106a-363 cluster may contribute to inhibition of proliferation by decreasing expression of several sibling miRNAs encoded by miR-17-92 or by the miR-106b-25 cluster. The inhibition of proliferation observed in miR-19a-mimic transfectants is likely caused by the miR-19a-dependent increase in the levels of miR-20b and miR-106a. Bioinformatic analysis of differentially expressed miRNAs from miR-106a, miR-20b and miR-363-5p transfectants, but not miR-92a transfectants, yielded significant associations to “Cellular Growth and Proliferation” and “Cell Cycle.” Western blotting results showed that levels of affected proteins to differ between transfectants, suggesting that different anti-proliferative mechanisms may operate in these transfectants. PMID:25202322

[EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE].

PubMed

Wu, Jun; Tang, Huiqin; Liu, Qun; Gan, Dingyun; Zhou, Man

2016-08-08

To investigate the effect of α-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet. Sixty male C57BL/6J mice weighting 200-300 g were randomly divided into model group (control group, n =15), α-lipoic acid-treated model group ( n =15), miR-29b mimic group ( n =15), and miR-29b mimic negative control group (NC group, n =15). All animals received intraperitoneal injection of streptozocin to establish the diabetic model. Then, a full thickness wound of 5 mm×2 mm in size was created at 4 weeks after modeling. All mice were administrated with high-sugar-fat-diet. At the same day after modeling, α-lipoic acid-treated model group was continuously given intravenous injection of 100 mg/(kg·d) α-lipoic acid for 14 days; miR-29b mimic group and NC group received the tail intravenous injection of lentiviral vector for miR-29b mimic and miR-29b mimic negative control (a total of 2×10 7 TU), respectively, with the treatment of α-lipoic acid. The wound healing was observed and wound area was measured at 7 and 14 days. The wound tissues were harvested to detect the levels of superoxide dismutase (SOD) and glutathione (GSH) using xanthine oxidase method and 5, 5-dithiobis-2-nitrobenzoic acid staining method at 14 days. At the same day, 7, and 14 days after modeling, the relative miR-29b expression in wound tissues from control and α-lipoic acid-treated model groups was detected by real-time fluorescence quantitative PCR. All mice survived to the experiment end. The wound healing was faster in α-lipoic acid-treated group than control group. At 7 and 14 days, the relative wound area and miR-29b expression level were significantly lower, while the contents of SOD and GSH were significantly higher in α-lipoic acid-treated group than control group ( P <0.05). In addition, miR-29b mimic group had significantly increased relative wound area and significantly decreased the contents of SOD and GSH when compared with NC group at 7 and 14 days ( P <0.05). α-lipoic acid could inhibit oxidative stress and promote diabetic wound healing by suppressing expression of miR-29b in mice.

Small molecule mimics of DFTamP1, a database designed anti-Staphylococcal peptide

PubMed Central

Dong, Yuxiang; Lushnikova, Tamara; Golla, Radha M.; Wang, Xiaofang; Wang, Guangshun

2017-01-01

Antimicrobial peptides (AMPs) are important templates for developing new antimicrobial agents. Previously, we developed a database filtering technology that enabled us to design a potent anti-Staphylococcal peptide DFTamP1. Using this same design approach, we now report the discovery of a new class of bis-indole diimidazolines as AMP small molecule mimics. The best compound killed multiple S. aureus clinical strains in both planktonic and biofilm forms. The compound appeared to target bacterial membranes with antimicrobial activity and membrane permeation ability similar to daptomycin. PMID:28011203

Small cell lung cancer growth is inhibited by miR-342 through its effect of the target gene IA-2.

PubMed

Xu, Huanyu; Cai, Tao; Carmona, Gilberto N; Abuhatzira, Liron; Notkins, Abner L

2016-09-26

Small cell lung cancers (SCLC) are tumors of neuroendocrine origin. Previous in vitro studies from our laboratory showed that SCLC expresses high levels of the transmembrane dense core vesicle protein IA-2 (islet cell antigen-2) as compared to normal lung cells. IA-2, through its effect on dense core vesicles (DCVs), is known to be involved in the secretion of hormones and neurotransmitters. It is believed that the dysregulated release of the neurotransmitter Acetylcholine (ACh) by DCVs has an autocrine effect on SCLC cell growth. Recently, we found that IA-2 is a target of the microRNA miR-342 and that miR-342 mimics suppress the expression of IA-2. The present experiments were initiated to see whether IA-2 and/or miR-342 affect the growth of SCLC. SCLC cell growth was evaluated following the knockdown of endogenous IA-2 with RNAi or by overexpressing miR-342 with a mimic. The secretion and content of ACh in SCLC cells was analyzed using a human acetylcholine ELISA (enzyme-linked immunosorbent assay) kit. The knockdown of endogenous IA-2 by RNAi reduced SCLC cell growth within 4 days by 40 % or more. Similar results were obtained when these cell lines were transfected with a miR-342 mimic. The knockdown of IA-2 by RNAi or miR-342 with a mimic also resulted in a significant decrease in the secretion of ACh, one of the autocrine hormones secreted by SCLC. Further studies revealed that the growth of SCLC cell lines that had been treated with the miR-342 mimic was restored to nearly normal levels by treatment with ACh. Our studies show for the first time that both miR-342 and its target gene IA-2 are involved in the growth process of SCLC cells and act by their effect on autocrine secretion. These findings point to possible new therapeutic approaches for the treatment of autocrine-induced tumor proliferation.

[Modulation of TLR-4/MyD88 signaling cascade by miR-21 is involved in airway immunologic dysfunction induced by cold air exposure].

PubMed

Xu, Rui; Huang, Huaping; Han, Zhong; Li, Minchao; Zhou, Xiangdong

2016-01-01

To investigate the role of miR-21 in airway immunologic dysfunction induced by cold air irritation. Immortalized human airway epithelial cell lines BEAS-2B and 16HBE cells were cultured in air-liquid phases. The differential expressions of endogenous miR-21, miR-164, and miR-155 in the cells induced by cold air exposure for different time were detected by real-time PCR. The reporter plasmid containing wild-type or mutated 3'UTR of TLR-4 were constructed and co-transfected into BEAS-2B cells or 16HBE cells together with miR-21 mimic, miR-21 mimic control, miR-21 inhibitor, or miR-21 inhibitor control. Following the transfection, dual luciferase reporter assay was performed to verify the action of miR-21 on TLR-4. miR-21 mimic, miR-21 mimic control, miR-21 inhibitor, and miR-21 inhibitor control were transfected via lipofectamine 2000 in BEAS-2B or 16HBE cells that were subsequently exposed to a temperature at 37 degrees celsius; or cold irritation (30 degrees celsius;), and the protein levels of TLR-4/MyD88 were detected by Western blotting. Cold irritation caused a time- dependent up-regulation of miR-21 in both BEAS-2B and 16HBE cells (P<0.05) without obviously affecting the expressions of miR-164 and miR-155. Dual luciferase reporter assay demonstrated a direct combination of miR-21 and its target protein TLR-4. The synthesis levels of TLR-4/MyD88 protein were decreased in miR-21 mimic group even at a routine culture temperature (P<0.05), as also seen in cells with cold irritation (P<0.05). Treatment with the miR-21 inhibitor partially attenuated cold irritation-induced down-regulation of TLR-4/MyD88 protein (P<0.05). Cold air irritation-induced airway immunologic dysfunction is probably associated with TLR-4/MyD88 down-regulation by an increased endogenic miR-21.

miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

PubMed

Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

2017-10-31

A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

Regulation of tumorigenesis and metastasis of hepatocellular carcinoma tumor endothelial cells by microRNA-3178 and underlying mechanism

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

Li, Wei; Shen, Shiqiang, E-mail: shenshiqiang2014@hotmail.com; Wu, Shanmin

2015-08-28

This study explored the effects of microRNA-3178 (miR-3178) on hepatocellular carcinoma (HCC) tumor endothelial cells (TECs) and on the target mRNA. Real-time polymerase chain reaction (PCR) was performed to detect the differential expression of miR-3178 in hepatic sinusoidal endothelial cells (HSECs) and HCC TECs. Furthermore, HCC TECs were transfected with miR-3178 mimic/inhibitor or their respective negative controls. The expression of miR-3178 before and after transfection was confirmed through RT-PCR. The effects of miR-3178 on the proliferation, apoptosis, cell cycle, invasion, migration, and angiogenesis of HCC TECs were also investigated through methyl thiazol tetrazolium assay, flow cytometry, matrigel invasion assay, transwellmore » migration assay, and tube formation assay. Early growth responsive gene 3 (EGR3), as the putative target of miR-3178, was detected through RT-PCR and Western blot. Compared with HSECs, HCC TECs had lower miR-3178 expression levels (P < 0.001). MiR-3178 mimic inhibited proliferation, arrested cell cycle in G1 phase, and increased apoptosis. The numbers of migrated and invaded cells and capillary-like structures were significantly less in the mimic group than in the other groups. MiR-3178 mimic significantly decreased the mRNA and protein expression levels of EGR3. By contrast, miR-3178 inhibitor induced opposite effects. We conclude that miR-3178 was lowly expressed in HCC TECs, and miR-3178 mimic specifically inhibited the proliferation, migration, invasion, and angiogenesis and promoted the apoptosis and G1 phase arrest of HCC TECs in vitro through the inhibition of EGR3 expression. Thus, miR-3178 might be a critical target in HCC therapy. - Highlights: • MiR-3178 is significantly low-expression in HCC TECs. • MiR-3178 acts as a tumor suppressor to inhibit tumorigenesis and metastasis. • MiR-3178 inhibit angiogenesis of HCC TECs. • EGR3 may be a target gene of miR-3178. • MiR-3178 may have therapeutic application for treatment of HCC.« less

Accuracy and efficiency of computer-aided anatomical analysis using 3D visualization software based on semi-automated and automated segmentations.

PubMed

An, Gao; Hong, Li; Zhou, Xiao-Bing; Yang, Qiong; Li, Mei-Qing; Tang, Xiang-Yang

2017-03-01

We investigated and compared the functionality of two 3D visualization software provided by a CT vendor and a third-party vendor, respectively. Using surgical anatomical measurement as baseline, we evaluated the accuracy of 3D visualization and verified their utility in computer-aided anatomical analysis. The study cohort consisted of 50 adult cadavers fixed with the classical formaldehyde method. The computer-aided anatomical analysis was based on CT images (in DICOM format) acquired by helical scan with contrast enhancement, using a CT vendor provided 3D visualization workstation (Syngo) and a third-party 3D visualization software (Mimics) that was installed on a PC. Automated and semi-automated segmentations were utilized in the 3D visualization workstation and software, respectively. The functionality and efficiency of automated and semi-automated segmentation methods were compared. Using surgical anatomical measurement as a baseline, the accuracy of 3D visualization based on automated and semi-automated segmentations was quantitatively compared. In semi-automated segmentation, the Mimics 3D visualization software outperformed the Syngo 3D visualization workstation. No significant difference was observed in anatomical data measurement by the Syngo 3D visualization workstation and the Mimics 3D visualization software (P>0.05). Both the Syngo 3D visualization workstation provided by a CT vendor and the Mimics 3D visualization software by a third-party vendor possessed the needed functionality, efficiency and accuracy for computer-aided anatomical analysis. Copyright © 2016 Elsevier GmbH. All rights reserved.

Molecular Dynamics Studies of Proton Transport in Hydrogenase and Hydrogenase Mimics.

PubMed

Ginovska, B; Raugei, S; Shaw, W J

2016-01-01

There is extensive interest in hydrogenases based on their ability to rapidly and efficiently interconvert H2 with protons and electrons, and their (typically) superior function relative to molecular mimics. Understanding the function of enzymes is one approach to implementing design features to make better catalysts and is an approach we have implemented in our work. In this review, we will discuss our efforts to develop design principles from enzymes, with specific focus on proton transport. We will also present computational studies of the mimics we have investigated with similar methodologies. We will discuss the mechanisms used by small scaffolds on molecular mimics which in many cases are surprisingly similar to those used by nature, while in other cases, computational analysis allowed us to reveal an unexpected role. Computational methods provide one of the best ways, and in some cases, the only way, to gain insight into the mechanistic details of enzymes. In this review, we illustrate the general computational strategy we used to study the proton pathway of [FeFe]-hydrogenase, and the similar strategy to investigate small molecules. We present the main results we obtained and how our computational work stimulated or worked in concert with experimental investigations. We also focus on estimation of errors and convergence of properties in the simulations. These studies demonstrate the powerful results that can be obtained by the close pairing of experimental and theoretical approaches. Copyright © 2016 Elsevier Inc. All rights reserved. Battelle, operator of PNNL, under Contract No: DE-AC05-76RL01830 with US DoE.

Graphene-palladium nanowires based electrochemical sensor using ZnFe2O4-graphene quantum dots as an effective peroxidase mimic.

PubMed

Liu, Weiyan; Yang, Hongmei; Ma, Chao; Ding, Ya-nan; Ge, Shenguang; Yu, Jinghua; Yan, Mei

2014-12-10

We proposed an electrochemical DNA sensor by using peroxidase-like magnetic ZnFe2O4-graphene quantum dots (ZnFe2O4/GQDs) nanohybrid as a mimic enzymatic label. Aminated graphene and Pd nanowires were successively modified on glassy carbon electrode, which improved the electronic transfer rate as well as increased the amount of immobilized capture ssDNA (S1). The nanohybrid ZnFe2O4/GQDs was prepared by assembling the GQDs on the surface of ZnFe2O4 through a photo-Fenton reaction, which was not only used as a mimic enzyme but also as a carrier to label complementary ssDNA (S3). By synergistically integrating highly catalytically activity of nano-sized GQDs and ZnFe2O4, the nanohybrid possessed highly-efficient peroxidase-like catalytic activity which could produce a large current toward the reduction of H2O2 for signal amplification. Thionine was used as an excellent electron mediator. Compared with traditional enzyme labels, the mimic enzyme ZnFe2O4/GQDs exhibited many advantages such as environment friendly and better stability. Under the optimal conditions, the approach provided a wide linear range from 10(-16) to 5×10(-9) M and low detection limit of 6.2×10(-17) M. The remarkable high catalytic capability could allow the nanohybrid to replace conventional peroxidase-based assay systems. The new, robust and convenient assay systems can be widely utilized for the identification of other target molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

PubMed

Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

2018-01-16

Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats

PubMed Central

Jickling, Glen C; Ander, Bradley P; Hull, Heather; Zhan, Xinhua; Cox, Christopher; Shroff, Natasha; Dykstra-Aiello, Cheryl; Stamova, Boryana; Sharp, Frank R

2015-01-01

Because our recent studies have demonstrated that miR-122 decreased in whole blood of patients and in whole blood of rats following ischemic stroke, we tested whether elevating blood miR-122 would improve stroke outcomes in rats. Young adult rats were subjected to a temporary middle cerebral artery occlusion (MCAO) or sham operation. A polyethylene glycol-liposome-based transfection system was used to administer a miR-122 mimic after MCAO. Neurological deficits, brain infarction, brain vessel integrity, adhesion molecule expression and expression of miR-122 target and indirect-target genes were examined in blood at 24 h after MCAO with or without miR-122 treatment. miR-122 decreased in blood after MCAO, whereas miR-122 mimic elevated miR-122 in blood 24 h after MCAO. Intravenous but not intracerebroventricular injection of miR-122 mimic decreased neurological deficits and brain infarction, attenuated ICAM-1 expression, and maintained vessel integrity after MCAO. The miR-122 mimic also down-regulated direct target genes (e.g. Vcam1, Nos2, Pla2g2a) and indirect target genes (e.g. Alox5, Itga2b, Timp3, Il1b, Il2, Mmp8) in blood after MCAO which are predicted to affect cell adhesion, diapedesis, leukocyte extravasation, eicosanoid and atherosclerosis signaling. The data show that elevating miR-122 improves stroke outcomes and we postulate this occurs via downregulating miR-122 target genes in blood leukocytes. PMID:26661204

The Functionality of Spontaneous Mimicry and Its Influences on Affiliation: An Implicit Socialization Account

PubMed Central

Kavanagh, Liam C.; Winkielman, Piotr

2016-01-01

There is a broad theoretical and empirical interest in spontaneous mimicry, or the automatic reproduction of a model’s behavior. Evidence shows that people mimic models they like, and that mimicry enhances liking for the mimic. Yet, there is no satisfactory account of this phenomenon, especially in terms of its functional significance. While affiliation is often cited as the driver of mimicry, we argue that mimicry is primarily driven by a learning process that helps to produce the appropriate bodily and emotional responses to relevant social situations. Because the learning process and the resulting knowledge is implicit, it cannot easily be rejected, criticized, revised, and employed by the learner in a deliberative or deceptive manner. We argue that these characteristics will lead individuals to preferentially mimic ingroup members, whose implicit information is worth incorporating. Conversely, mimicry of the wrong person is costly because individuals will internalize “bad habits,” including emotional reactions and mannerisms indicating wrong group membership. This pattern of mimicry, in turn, means that observed mimicry is an honest signal of group affiliation. We propose that the preferences of models for the mimic stems from this true signal value. Further, just like facial expressions, mimicry communicates a genuine disposition when it is truly spontaneous. Consequently, perceivers are attuned to relevant cues such as appropriate timing, fidelity, and selectivity. Our account, while assuming no previously unknown biological endowments, also explains greater mimicry of powerful people, and why affiliation can be signaled by mimicry of seemingly inconsequential behaviors. PMID:27064398

Comparison of 3D reconstruction of mandible for pre-operative planning using commercial and open-source software

NASA Astrophysics Data System (ADS)

Abdullah, Johari Yap; Omar, Marzuki; Pritam, Helmi Mohd Hadi; Husein, Adam; Rajion, Zainul Ahmad

2016-12-01

3D printing of mandible is important for pre-operative planning, diagnostic purposes, as well as for education and training. Currently, the processing of CT data is routinely performed with commercial software which increases the cost of operation and patient management for a small clinical setting. Usage of open-source software as an alternative to commercial software for 3D reconstruction of the mandible from CT data is scarce. The aim of this study is to compare two methods of 3D reconstruction of the mandible using commercial Materialise Mimics software and open-source Medical Imaging Interaction Toolkit (MITK) software. Head CT images with a slice thickness of 1 mm and a matrix of 512x512 pixels each were retrieved from the server located at the Radiology Department of Hospital Universiti Sains Malaysia. The CT data were analysed and the 3D models of mandible were reconstructed using both commercial Materialise Mimics and open-source MITK software. Both virtual 3D models were saved in STL format and exported to 3matic and MeshLab software for morphometric and image analyses. Both models were compared using Wilcoxon Signed Rank Test and Hausdorff Distance. No significant differences were obtained between the 3D models of the mandible produced using Mimics and MITK software. The 3D model of the mandible produced using MITK open-source software is comparable to the commercial MIMICS software. Therefore, open-source software could be used in clinical setting for pre-operative planning to minimise the operational cost.

Representing life in the Earth system with soil microbial functional traits in the MIMICS model

NASA Astrophysics Data System (ADS)

Wieder, W. R.; Grandy, A. S.; Kallenbach, C. M.; Taylor, P. G.; Bonan, G. B.

2015-02-01

Projecting biogeochemical responses to global environmental change requires multi-scaled perspectives that consider organismal diversity, ecosystem processes and global fluxes. However, microbes, the drivers of soil organic matter decomposition and stabilization, remain notably absent from models used to project carbon cycle-climate feedbacks. We used a microbial trait-based soil carbon (C) model, with two physiologically distinct microbial communities to improve current estimates of soil C storage and their likely response to perturbations. Drawing from the application of functional traits used to model other ecosystems, we incorporate copiotrophic and oligotrophic microbial functional groups in the MIcrobial-MIneral Carbon Stabilization (MIMICS) model, which incorporates oligotrophic and copiotrophic functional groups, akin to "gleaner" vs. "opportunist" plankton in the ocean, or r vs. K strategists in plant and animals communities. Here we compare MIMICS to a conventional soil C model, DAYCENT, in cross-site comparisons of nitrogen (N) enrichment effects on soil C dynamics. MIMICS more accurately simulates C responses to N enrichment; moreover, it raises important hypotheses involving the roles of substrate availability, community-level enzyme induction, and microbial physiological responses in explaining various soil biogeochemical responses to N enrichment. In global-scale analyses, we show that current projections from Earth system models likely overestimate the strength of the land C sink in response to increasing C inputs with elevated carbon dioxide (CO2). Our findings illustrate that tradeoffs between theory and utility can be overcome to develop soil biogeochemistry models that evaluate and advance our theoretical understanding of microbial dynamics and soil biogeochemical responses to environmental change.

Enhanced Peroxidase-Like Performance of Gold Nanoparticles by Hot Electrons.

PubMed

Wang, Chen; Shi, Yi; Dan, Yuan-Yuan; Nie, Xing-Guo; Li, Jian; Xia, Xing-Hua

2017-05-17

Enzyme mimics have been widely used as alternatives to natural enzymes. However, the catalytic performances of enzyme mimics are often decreased due to different spatial structures or absence of functional groups compared to natural enzymes. Here, we report a highly efficient enzyme-like catalytic performance of gold nanoparticles (AuNPs) by visible-light stimulation. The enzyme-like reaction is evaluated by the catalytic reaction of AuNPs oxidizing a typical chromogenic substrate 3,3',5,5'-tetramethylbenzydine (TMB) with hydrogen peroxide as an oxidant. From investigations of the wavelength-dependent reaction rate, radical capture, hole-donor addition, and dark-field scattering spectroscopy experiments, it is revealed that the strong plasmonic absorption of AuNPs facilitates generation of hot electrons, which are transfered from AuNPs to the adsorbed reactant molecule, greatly promoting the catalytic performance of the enzyme-like catalytic reaction. The present work provides a simple method for improving the performance of enzyme mimics, which is expected to find further application in the field of plasmon-enhanced biocatalysis and biosensors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual-functional Pt-on-Pd supported on reduced graphene oxide hybrids: peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic.

PubMed

Zhang, Xiahong; Wu, Genghuang; Cai, Zhixiong; Chen, Xi

2015-03-01

In this study, a facile hydrothermal method was developed to synthesize Pt-on-Pd supported on reduced graphene oxide (Pt-on-Pd/RGO) hybrids. Because of the synergistic effect between Pt-on-Pd and RGO, the obtained Pt-on-Pd/RGO had superior peroxidase-mimic activities in H2O2 reduction and TMB oxidation. The reaction medium was optimized and a sensing approach for H2O2 was developed with a linear range from 0.98 to 130.7 μM of H2O2. In addition, the characteristic of electrocatalytic oxidation of methanol was investigated. The peak current density value, j(f), for the Pt-on-Pd/RGO hybrid (328 mA mg(Pt)(-1)) was about 1.85 fold higher than that of commercial Pt black (177 mA mg(Pt)(-1)) and, also, more durable electrocatalytic activity could be obtained. For the first time, the dual-functional Pt-on-Pd/RGO with peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic was reported. Copyright © 2014 Elsevier B.V. All rights reserved.

Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch

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

Howe, John A.; Xiao, Li; Fischmann, Thierry O.

2016-08-02

Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil ismore » structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.« less

Aortic atherosclerotic plaque detection using a multiwavelength handheld photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Hirano, Susumu; Namita, Takeshi; Kondo, Kengo; Yamakawa, Makoto; Shiina, Tsuyoshi

2016-03-01

Patients affected by diseases caused by arteriosclerosis are increasing. Atherosclerosis, which is becoming an especially difficult health problem, forms plaques from lipids such as cholesterol located in walls of the aorta, cerebral artery, and coronary artery. Because lipid-rich plaques are vulnerable and because arterial rupture causes acute vascular occlusion, early detection is crucially important to prevent plaque growth and rupture. Ultrasound systems can detect plaques but cannot discriminate between vulnerable and equable plaques. To evaluate plaques non-invasively and easily, we developed a handheld photoacoustic imaging device. Its usefulness was verified in phantom experiments with a bovine aorta in which mimic plaque had been embedded. Photoacoustic images taken at wavelengths that produce high light absorbance by lipids show strong photoacoustic signals from the boundary of the mimic plaque. Results confirmed that our system can evaluate plaque properties by analysis with the photoacoustic spectrum. The effects of surrounding tissues and tissue components on plaque evaluation were investigated using a layered phantom. The mimic plaque located under a 6 mm blood layer was also evaluated. Results of these analyses demonstrate the system's usefulness.

Context-dependent vocal mimicry in a passerine bird.

PubMed

Goodale, Eben; Kotagama, Sarath W

2006-04-07

How do birds select the sounds they mimic, and in what contexts do they use vocal mimicry? Some birds show a preference for mimicking other species' alarm notes, especially in situations when they appear to be alarmed. Yet no study has demonstrated that birds change the call types they mimic with changing contexts. We found that greater racket-tailed drongos (Dicrurus paradiseus) in the rainforest of Sri Lanka mimic the calls of predators and the alarm-associated calls of other species more often than would be expected from the frequency of these sounds in the acoustic environment. Drongos include this alarm-associated mimicry in their own alarm vocalizations, while incorporating other species' songs and contact calls in their own songs. Drongos show an additional level of context specificity by mimicking other species' ground predator-specific call types when mobbing. We suggest that drongos learn other species' calls and their contexts while interacting with these species in mixed flocks. The drongos' behaviour demonstrates that alarm-associated calls can have learned components, and that birds can learn the appropriate usage of calls that encode different types of information.

Context-dependent vocal mimicry in a passerine bird

PubMed Central

Goodale, Eben; Kotagama, Sarath W

2005-01-01

How do birds select the sounds they mimic, and in what contexts do they use vocal mimicry? Some birds show a preference for mimicking other species' alarm notes, especially in situations when they appear to be alarmed. Yet no study has demonstrated that birds change the call types they mimic with changing contexts. We found that greater racket-tailed drongos (Dicrurus paradiseus) in the rainforest of Sri Lanka mimic the calls of predators and the alarm-associated calls of other species more often than would be expected from the frequency of these sounds in the acoustic environment. Drongos include this alarm-associated mimicry in their own alarm vocalizations, while incorporating other species' songs and contact calls in their own songs. Drongos show an additional level of context specificity by mimicking other species' ground predator-specific call types when mobbing. We suggest that drongos learn other species' calls and their contexts while interacting with these species in mixed flocks. The drongos' behaviour demonstrates that alarm-associated calls can have learned components, and that birds can learn the appropriate usage of calls that encode different types of information. PMID:16618682

Diversification patterns of pebble-mimic dragons are consistent with historical disruption of important habitat corridors in arid Australia.

PubMed

Shoo, L P; Rose, R; Doughty, P; Austin, J J; Melville, J

2008-08-01

The pebble-mimic dragon lineage of Tympanocryptis is widely distributed in the stony, or 'gibber', deserts of Australia but is noticeably absent from intersecting areas of sand deserts. Past fluctuations in the extent and configuration of sandy desert habitat barriers are likely to have been an import factor promoting genetic differentiation in this group. We sequenced a approximately 1400bp region of mitochondrial DNA and a approximately 1400bp nuclear gene (RAG-1) to investigate phylogeographic structuring of species of pebble-mimic dragons. Our topology indicates an early split in this lineage between eastern and western parts of the arid zone that probably dates to the mid-Miocene. This split corresponds directly with large expanses of contemporary sandy habitat in the form of Great Sandy and Great Victoria Deserts. Our data indicate that this biogeographic barrier established very early on in the development of the arid zone and has persisted to present. Additional genetic structuring in the absence of recognized barriers suggests that an expanded view of potential habitat barriers in the arid zone is required.

Control of C-H Bond Activation by Mo-Oxo Complexes: pKa or Bond Dissociation Free Energy (BDFE)?

PubMed

Nazemi, Azadeh; Cundari, Thomas R

2017-10-16

A density functional theory (DFT) study (BMK/6-31+G(d)) was initiated to investigate the activation of benzylic carbon-hydrogen bonds by a molybdenum-oxo complex with a potentially redox noninnocent supporting ligand-a simple mimic of the active species of the enzyme ethylbenzene dehydrogenase (EBDH)-through deprotonation (C-H bond heterolysis) or hydrogen atom abstraction (C-H bond homolysis) routes. Activation free-energy barriers for neutral and anionic Mo-oxo complexes were high, but lower for anionic complexes than neutral complexes. Interesting trends as a function of substituents were observed that indicated significant H δ+ character in the transition states (TS), which was further supported by the preference for [2 + 2] addition over HAA for most complexes. Hence, it was hypothesized that C-H activation by these EBDH mimics is controlled more by the pK a than by the bond dissociation free energy of the C-H bond being activated. Therefore, the results suggest promising pathways for designing more efficient and selective catalysts for hydrocarbon oxidation based on EBDH active-site mimics.

De Novo Design of Protein Mimics of B-DNA

PubMed Central

Yüksel, Deniz; Bianco, Piero R.; Kumar, Krishna

2015-01-01

Structural mimicry of DNA is utilized in nature as a strategy to evade molecular defences mounted by host organisms. One such example is the protein Ocr – the first translation product to be expressed as the bacteriophage T7 infects E. coli. The structure of Ocr reveals an intricate and deliberate arrangement of negative charges that endows it with the ability to mimic ∼24 base pair stretches of B–DNA. This uncanny resemblance to DNA enables Ocr to compete in binding the type I restriction modification (R/M) system, and neutralizes the threat of hydrolytic cleavage of viral genomic material. Here, we report the de novo design and biophysical characterization of DNA mimicking peptides, and describe the inhibitory action of the designed helical bundles on a type I R/M enzyme, EcoR124I. This work validates the use of charge patterning as a design principle for creation of protein mimics of DNA, and serves as a starting point for development of therapeutic peptide inhibitors against human pathogens that employ molecular camouflage as part of their invasion stratagem. PMID:26568416

Diagnostic confounders of chronic widespread pain: not always fibromyalgia

PubMed Central

Häuser, Winfried; Perrot, Serge; Sommer, Claudia; Shir, Yoram; Fitzcharles, Mary-Ann

2017-01-01

Abstract Introduction: Chronic widespread pain (CWP) is the defining feature of fibromyalgia (FM), a worldwide prevalent condition. Chronic widespread pain is, however, not pathognomonic of FM, and other conditions may present similarly with CWP, requiring consideration of a differential diagnosis. Objectives: To conduct a literature search to identify medical conditions that may mimic FM and have highlighted features that may differentiate these various conditions from FM. Methods: A comprehensive literature search from 1990 through September 2016 was conducted to identify conditions characterized by CWP. Results: Conditions that may mimic FM may be categorized as musculoskeletal, neurological, endocrine/metabolic, psychiatric/psychological, and medication related. Characteristics pertaining to the most commonly identified confounding diagnoses within each category are discussed; clues to enable clinical differentiation from FM are presented; and steps towards a diagnostic algorithm for mimicking conditions are presented. Conclusion: Although the most likely reason for a complaint of CWP is FM, this pain complaint can be a harbinger of illness other than FM, prompting consideration of a differential diagnosis. This review should sensitize physicians to a broad spectrum of conditions that can mimic FM. PMID:29392213

The mimetic repertoire of the spotted bowerbird Ptilonorhynchus maculatus

NASA Astrophysics Data System (ADS)

Kelley, Laura A.; Healy, Susan D.

2011-06-01

Although vocal mimicry in songbirds is well documented, little is known about the function of such mimicry. One possibility is that the mimic produces the vocalisations of predatory or aggressive species to deter potential predators or competitors. Alternatively, these sounds may be learned in error as a result of their acoustic properties such as structural simplicity. We determined the mimetic repertoires of a population of male spotted bowerbirds Ptilonorhynchus maculatus, a species that mimics predatory and aggressive species. Although male mimetic repertoires contained an overabundance of vocalisations produced by species that were generally aggressive, there was also a marked prevalence of mimicry of sounds that are associated with alarm such as predator calls, alarm calls and mobbing calls, irrespective of whether the species being mimicked was aggressive or not. We propose that it may be the alarming context in which these sounds are first heard that may lead both to their acquisition and to their later reproduction. We suggest that enhanced learning capability during acute stress may explain vocal mimicry in many species that mimic sounds associated with alarm.

The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

PubMed Central

Ko, Tzu-Ping; Liao, Yi-Ting; Hsu, Kai-Cheng

2017-01-01

DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms. PMID:29220372

The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer.

PubMed

Yin, Juxin; Wang, Bingmei; Zhu, Xuejun; Qu, Xiaonan; Huang, Yi; Lv, Shaowu; Mu, Ying; Luo, Guimin

2017-09-08

Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications.

[Establishment of a 3D finite element model of human skull using MSCT images and mimics software].

PubMed

Huang, Ping; Li, Zheng-dong; Shao, Yu; Zou, Dong-hua; Liu, Ning-guo; Li, Li; Chen, Yuan-yuan; Wan, Lei; Chen, Yi-jiu

2011-02-01

To establish a human 3D finite element skull model, and to explore its value in biomechanics analysis. The cadaveric head was scanned and then 3D skull model was created using Mimics software based on 2D CT axial images. The 3D skull model was optimized by preprocessor along with creation of the surface and volume meshes. The stress changes, after the head was struck by an object or the head hit the ground directly, were analyzed using ANSYS software. The original 3D skull model showed a large number of triangles with a poor quality and high similarity with the real head, while the optimized model showed high quality surface and volume meshes with a small number of triangles comparatively. The model could show the local and global stress changes effectively. The human 3D skull model can be established using MSCT and Mimics software and provides a good finite element model for biomechanics analysis. This model may also provide a base for the study of head stress changes following different forces.

Intact Rapid Facial Mimicry as well as Generally Reduced Mimic Responses in Stable Schizophrenia Patients

PubMed Central

Chechko, Natalya; Pagel, Alena; Otte, Ellen; Koch, Iring; Habel, Ute

2016-01-01

Spontaneous emotional expressions (rapid facial mimicry) perform both emotional and social functions. In the current study, we sought to test whether there were deficits in automatic mimic responses to emotional facial expressions in patients (15 of them) with stable schizophrenia compared to 15 controls. In a perception-action interference paradigm (the Simon task; first experiment), and in the context of a dual-task paradigm (second experiment), the task-relevant stimulus feature was the gender of a face, which, however, displayed a smiling or frowning expression (task-irrelevant stimulus feature). We measured the electromyographical activity in the corrugator supercilii and zygomaticus major muscle regions in response to either compatible or incompatible stimuli (i.e., when the required response did or did not correspond to the depicted facial expression). The compatibility effect based on interactions between the implicit processing of a task-irrelevant emotional facial expression and the conscious production of an emotional facial expression did not differ between the groups. In stable patients (in spite of a reduced mimic reaction), we observed an intact capacity to respond spontaneously to facial emotional stimuli. PMID:27303335

Testing Group Mean Differences of Latent Variables in Multilevel Data Using Multiple-Group Multilevel CFA and Multilevel MIMIC Modeling.

PubMed

Kim, Eun Sook; Cao, Chunhua

2015-01-01

Considering that group comparisons are common in social science, we examined two latent group mean testing methods when groups of interest were either at the between or within level of multilevel data: multiple-group multilevel confirmatory factor analysis (MG ML CFA) and multilevel multiple-indicators multiple-causes modeling (ML MIMIC). The performance of these methods were investigated through three Monte Carlo studies. In Studies 1 and 2, either factor variances or residual variances were manipulated to be heterogeneous between groups. In Study 3, which focused on within-level multiple-group analysis, six different model specifications were considered depending on how to model the intra-class group correlation (i.e., correlation between random effect factors for groups within cluster). The results of simulations generally supported the adequacy of MG ML CFA and ML MIMIC for multiple-group analysis with multilevel data. The two methods did not show any notable difference in the latent group mean testing across three studies. Finally, a demonstration with real data and guidelines in selecting an appropriate approach to multilevel multiple-group analysis are provided.

Controlling Surface Plasmons Through Covariant Transformation of the Spin-Dependent Geometric Phase Between Curved Metamaterials

NASA Astrophysics Data System (ADS)

Zhong, Fan; Li, Jensen; Liu, Hui; Zhu, Shining

2018-06-01

General relativity uses curved space-time to describe accelerating frames. The movement of particles in different curved space-times can be regarded as equivalent physical processes based on the covariant transformation between different frames. In this Letter, we use one-dimensional curved metamaterials to mimic accelerating particles in curved space-times. The different curved shapes of structures are used to mimic different accelerating frames. The different geometric phases along the structure are used to mimic different movements in the frame. Using the covariant principle of general relativity, we can obtain equivalent nanostructures based on space-time transformations, such as the Lorentz transformation and conformal transformation. In this way, many covariant structures can be found that produce the same surface plasmon fields when excited by spin photons. A new kind of accelerating beam, the Rindler beam, is obtained based on the Rindler metric in gravity. Very large effective indices can be obtained in such systems based on geometric-phase gradient. This general covariant design method can be extended to many other optical media.

Decidualized endometrioma during pregnancy: recognizing an imaging mimic of ovarian malignancy.

PubMed

Poder, Liina; Coakley, Fergus V; Rabban, Joseph T; Goldstein, Ruth B; Aziz, Seerat; Chen, Lee-may

2008-01-01

To present the ultrasound and magnetic resonance imaging findings that may allow for a prospective diagnosis and expectant management of decidualized endometriomas because the rare occurrence of decidualization in the ectopic endometrial stroma of an endometrioma during pregnancy can mimic ovarian cancer at imaging. Smooth lobulated mural nodules with prominent internal vascularity were noted in an apparent right ovarian endometrioma on serial ultrasound studies in a 34-year-old woman at 12, 21, 27, and 30 weeks of gestation. Magnetic resonance imaging demonstrated the nodules to be strikingly similar in intensity and texture to the decidualized endometrium in the uterus on T2-weighted sequences. A provisional diagnosis of decidualized endometrioma allowed for expectant management with immediate postpartum resection and confirmation of the diagnosis. Decidualized endometrioma can mimic ovarian malignancy during pregnancy, but a prospective diagnosis may be possible when solid smoothly lobulated nodules with prominent internal vascularity within an endometrioma are seen from early in pregnancy, and the nodules demonstrate marked similarity in signal intensity and texture with the decidualized endometrium in the uterus at magnetic resonance imaging.

Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

PubMed

Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

2013-01-16

Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

Actuation control of a PiezoMEMS biomimetic robotic jellyfish

NASA Astrophysics Data System (ADS)

Alejandre, Alvaro; Olszewski, Oskar; Jackson, Nathan

2017-06-01

Biomimetic micro-robots try to mimic the motion of a living system in the form of a synthetically developed microfabricated device. Dynamic motion of living systems have evolved through the years, but trying to mimic these motions is challenging. Micro-robotics are particular challenging as the fabrication of devices and controlling the motion in 3 dimensions is difficult. However, micro-scale robotics have potential to be used in a wide range of applications. MEMS based robots that can move and function in a liquid environment is of particular interest. This paper describes the development of a piezoMEMS based device that mimics the movement of a jellyfish. The paper focuses on the development of a finite element model that investigates a method of controlling the individual piezoelectric beams in order to create a jet propulsion motion, consisting of a quick excitation pulse followed by a slow recovery pulse in order to maximize thrust and velocity. By controlling the individual beams or legs of the jellyfish robot the authors can control the robot to move precisely in 3 dimensions.

Dense white trichome production by plants as possible mimicry of arthropod silk or fungal hyphae that deter herbivory.

PubMed

Yamazaki, Kazuo; Lev-Yadun, Simcha

2015-01-07

Some spiders are well-known to mimic flowers or other plant surfaces in order to be cryptic to both their prey and their predators. We propose that dense, thread-like white trichomes of some plants from Estonia, Greece, Israel and Japan visually mimic spider webs, lepidopteran and spider-mite web nests and plant-pathogenic fungi, and that it may result in reduced herbivory, since various herbivores avoid spider- or other arthropod webs to circumvent predation or toxic attacks, or refrain from colonizing plants that have already been occupied by other herbivores and pathogens. Spiders and other web-forming arthropods are also the prey of certain vertebrate predators and wasps, and therefore such predators may be attracted to these web-like plant structures and prey on the invertebrate herbivores occupying them. We do not dismiss the possibility that these web-like structures may also have other defensive or physiological functions or that they are not classic mimics but rather exploit the herbivore׳s perceptual state concerning the avoidance of potentially risky objects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wolff-Parkinson-white syndrome mimics a conduction disease.

PubMed

Marrakchi, S; Kammoun, I; Kachboura, S

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

Non-thermal plasma jet without electrical shock for biomedical applications

NASA Astrophysics Data System (ADS)

Baik, Ku Youn; Kang, Han Lim; Kim, Junseong; Park, Shin Young; Bang, Ji Yun; Uhm, Han S.; Choi, Eun Ha; Cho, Guangsup

2013-10-01

A plasma jet without an electrical shock was generated through a Y-shaped tube in which voltages with opposite phases were applied to a pair of tubes. The plasma plume generated at the intersection had a plasma potential of a 60-90 V and high concentrations of reactive species sufficient to induce a high level of lethality on gram-negative bacteria on a tissue mimic. The selective lethality of bacteria on an epithelial-cell-containing tissue mimic could be modulated using oxidant and antioxidant chemicals, thereby leading to the possibility of a shock-reduced plasma jet for biomedical applications.

Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications

PubMed Central

Siegfried, Elaine C.; Hebert, Adelaide A.

2015-01-01

Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD. These include inflammatory skin conditions, infections, infestations, malignancies, genetic disorders, immunodeficiency disorders, nutritional disorders, graft-versus-host disease, and drug eruptions. Familiarity of the spectrum of these diseases and their distinguishing features is critical for correct and timely diagnosis and optimal treatment. PMID:26239454

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae

PubMed Central

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition. PMID:28400786

Successful Treatment of Chromobacterium violaceum Sepsis in a South Indian Adult.

PubMed

Madi, Deepak R; Vidyalakshmi, K; Ramapuram, John; Shetty, Avinash K

2015-11-01

Infection due to Chromobacterium violaceum is rare. Diagnosis may be delayed since Chromobacterium sepsis may mimic melioidosis, especially in melioidosis-endemic areas. Management of Chromobacterium infection is challenging given the propensity of this pathogen to cause visceral abscesses, drug resistance, and relapse. Mortality rates are high despite treatment. We report a case of C. violaceum septicemia in an immunocompetent adult from south India, who was successfully treated with combination antibiotic therapy. Physicians in tropical and subtropical regions must be aware of C. violaceum infection as it can mimic melioidosis. © The American Society of Tropical Medicine and Hygiene.

Oxidoreductase mimic activity of natural pyrrhotite

NASA Astrophysics Data System (ADS)

Ibáñez de Aldecoa, A. L.; Velasco, F.; Menor-Salván, C.

2012-09-01

The theory of the chemo-autotrophic origin of life, also called the "iron-sulfur world hypothesis", proposes that the system FeS/FeS2 present in the primitive Earth crust gave the reductive power necessary to conduct the first protometabolic redox reactions. Some experimental studies demonstrated the redox activity of the FeS/SH2 system, but none of them used natural FeS. Here, we show that the iron sulfide mineral pyrrhotite is able to mimic the redox activity of the enzyme lactate dehydrogenase, which reversibly reduces the pyruvate in lactate, under prebiotic conditions with pyrite formation.

Integrating the glioblastoma microenvironment into engineered experimental models

PubMed Central

Xiao, Weikun; Sohrabi, Alireza; Seidlits, Stephanie K

2017-01-01

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed. PMID:28883992

Paintings, photographs, and computer graphics are calculated appearances

NASA Astrophysics Data System (ADS)

McCann, John

2012-03-01

Painters reproduce the appearances they see, or visualize. The entire human visual system is the first part of that process, providing extensive spatial processing. Painters have used spatial techniques since the Renaissance to render HDR scenes. Silver halide photography responds to the light falling on single film pixels. Film can only mimic the retinal response of the cones at the start of the visual process. Film cannot mimic the spatial processing in humans. Digital image processing can. This talk studies three dramatic visual illusions and uses the spatial mechanisms found in human vision to interpret their appearances.

Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation.

PubMed

Flemer, Stevenson; Wurthmann, Alexander; Mamai, Ahmed; Madalengoitia, José S

2008-10-03

A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.

Application of phage peptide display technology for the study of food allergen epitopes.

PubMed

Chen, Xueni; Dreskin, Stephen C

2017-06-01

Phage peptide display technology has been used to identify IgE-binding mimotopes (mimics of natural epitopes) that mimic conformational epitopes. This approach is effective in the characterization of those epitopes that are important for eliciting IgE-mediated allergic responses by food allergens and those that are responsible for cross-reactivity among allergenic food proteins. Application of this technology will increase our understanding of the mechanisms whereby food allergens elicit allergic reactions, will facilitate the discovery of diagnostic reagents and may lead to mimotope-based immunotherapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concerto catalysis--harmonising [NiFe]hydrogenase and NiRu model catalysts.

PubMed

Ichikawa, Koji; Nonaka, Kyoshiro; Matsumoto, Takahiro; Kure, Bunsho; Yoon, Ki-Seok; Higuchi, Yoshiki; Yagi, Tatsuhiko; Ogo, Seiji

2010-03-28

This communication reports the successful merging of the chemical properties of a natural [NiFe]hydrogenase (Desulfovibrio vulgaris Miyazaki F) and our previously reported [NiRu] hydrogenase-mimic. The catalytic activity of both the natural enzyme and the mimic is almost identical, with the exception of working pH ranges, and this allows us to use them simultaneously in the same reaction flask. In such a manner, isotope exchange between D(2) and H(2)O could be conducted over an extended pH range (about 2-10) in one pot under mild conditions at ambient temperature and pressure.

Radiology of pancreatic neoplasms: An update

PubMed Central

de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

2014-01-01

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis. PMID:25232458

Radiology of pancreatic neoplasms: An update.

PubMed

de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

2014-09-15

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis.

Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae.

PubMed

Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

2017-01-01

Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition.

Flight Control System for the CRCA (Control Reconfigurable Combat Aircraft) Using a Command Generator Tracker with PI (Plus Integral) Feedback and Kalman Filter. Volume 2

DTIC Science & Technology

1989-03-01

IAutomatic Control, AC-22, p 883-885, 1977 /Syntax check EIGA=EIG(A); EIGB=EIG(B); [M,N)=SIZE(EIGA); [PR] SIZE(EIGB); FOR 11I:M,FOR JlI:P,.... EIGAB=EIGA...AIM = implicit model A matrix I/ QI = weighting matrix, ouputs mimic model I/ RI = weighting matrix, controls mimic model // QIHAT = implicit cost II...the dimension is less than 1. // NINPUTS (the number of controls and outputs) is the flag for the dimensio // of the connections. /- // The name of

Distal muscle involvement in granulomatous myositis can mimic inclusion body myositis.

PubMed

Larue, Sandrine; Maisonobe, Thierry; Benveniste, Olivier; Chapelon-Abric, Catherine; Lidove, Olivier; Papo, Thomas; Eymard, Bruno; Dubourg, Odile

2011-06-01

The authors report on four patients aged over 50 with chronic myopathy suggestive of sporadic inclusion body myositis. They present progressive and selective weakness of the quadriceps femoris muscles. Asymmetrical and selective atrophy of the forearm muscles were noted in all, with more severe involvement of the flexors than the extensors. Biopsy revealed granulomatous myositis. Histological features of sporadic inclusion body myositis were lacking. Evidence for systemic sarcoidosis was found in one patient. Corticosteroid treatment was associated with a partial but significant improvement in two patients. Granulomatous myositis may mimic inclusion body myositis and may be steroid-responsive.

Bioactive Mimetics of Conotoxins and other Venom Peptides

PubMed Central

Duggan, Peter J.; Tuck, Kellie L.

2015-01-01

Ziconotide (Prialt®), a synthetic version of the peptide ω-conotoxin MVIIA found in the venom of a fish-hunting marine cone snail Conus magnus, is one of very few drugs effective in the treatment of intractable chronic pain. However, its intrathecal mode of delivery and narrow therapeutic window cause complications for patients. This review will summarize progress in the development of small molecule, non-peptidic mimics of Conotoxins and a small number of other venom peptides. This will include a description of how some of the initially designed mimics have been modified to improve their drug-like properties. PMID:26501323

Development of 3D out-of-plane SU-8 microlenses using modified micromolding in capillaries (MIMIC) technology

NASA Astrophysics Data System (ADS)

Llobera, A.; Wilke, R.; Johnson, D. W.; Büttgenbach, S.

2006-04-01

This paper describes a modification of the standard MIMIC technology, solving its main drawbacks, to define arrays of spherical or ellipsoidal microlenses. Perfectly symmetrical meniscuses have been obtained by using a XP SU-8 NO-2 layer beneath the PDMS mold. Moreover, the photostructurable properties of this polymer allow obtaining self-alignment structures for adequate fiber optics positioning. Microchannels ended with these meniscuses have been filled with standard SU-8 to obtain 3D microlenses. Agreement between theory and experimental results allows confirming the validity of the proposed technology.

Conformational analysis of endomorphin-2 analogs with phenylalanine mimics by NMR and molecular modeling.

PubMed

Shao, Xuan; Gao, Yanfeng; Zhu, Chuanjun; Liu, Xuehui; Yao, Jinlong; Cui, Yuxin; Wang, Rui

2007-05-15

We investigated a series of conformations of endomorphin-2 (EM-2) analogs substituted by phenylglycine (Phg) and homophenylalanine (Hfe) in the position 3 or 4 by two-dimensional (1)H NMR spectroscopy and molecular modeling. Evaluating the aromatic interactions and the dihedral angles in these phenylalanine mimics, we have observed that the conformations in trans isomer have varied from extended to folded as bioactivity decreases. It is suggested that the flexibility of aromatic side chain affects the backbone of EM-2 to adopt folded structures, which may block the ligands in binding to micro-opioid receptor.

Potent Inhibitors of the Hepatitis C Virus NS3 Protease: Design and Synthesis of Macrocyclic Substrate-Based [beta]-Strand Mimics

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

Goudreau, Nathalie; Brochu, Christian; Cameron, Dale R.

2008-06-30

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring {beta}-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.

Modern moulage: evaluating the use of 3-dimensional prosthetic mimics in a dermatology teaching program for second-year medical students.

PubMed

Garg, Amit; Haley, Heather-Lyn; Hatem, David

2010-02-01

To evaluate the effectiveness of a teaching method that uses 3-dimensional (3D) silicone-based prosthetic mimics of common serious lesions and eruptions and to compare learning outcomes with those achieved through the conventional method of lectures with 2-dimensional (2D) images. Prospective and comparative. University of Massachusetts Medical School. Ninety second-year medical students. A 1-hour teaching intervention using a lecture with 2D images (2D group) or using 3D prosthetic mimics of lesions and eruptions (3D group). Mean scores in the domains of morphology, lesion and rash recognition, lesion and rash management, and overall performance assessed at baseline, immediately after, and 3 months after each group's respective teaching intervention. Immediately after the teaching intervention, the 3D group had significantly higher mean percentage scores than did the 2D group for overall performance (71 vs 65, P = .03), lesion recognition (65 vs 56, P = .02), and rash management (80 vs 67, P = .01). Three months later, the 3D group still had significantly higher mean percentage scores than did the 2D group for lesion recognition (47 vs 40, P = .03). The 3D group better recognized lesions at 3 months compared with at baseline, whereas the 2D group was no better at recognizing lesions at 3 months compared with at baseline. Despite limited curricular time, the novel teaching method using 3D prosthetic mimics of lesions and eruptions improves immediate and long-term learning outcomes, in particular, lesion recognition. It is also a preferred teaching format among second-year medical students.

Blood Biomarkers for the Early Diagnosis of Stroke: The Stroke-Chip Study.

PubMed

Bustamante, Alejandro; López-Cancio, Elena; Pich, Sara; Penalba, Anna; Giralt, Dolors; García-Berrocoso, Teresa; Ferrer-Costa, Carles; Gasull, Teresa; Hernández-Pérez, María; Millan, Mónica; Rubiera, Marta; Cardona, Pedro; Cano, Luis; Quesada, Helena; Terceño, Mikel; Silva, Yolanda; Castellanos, Mar; Garces, Moisés; Reverté, Silvia; Ustrell, Xavier; Marés, Rafael; Baiges, Joan Josep; Serena, Joaquín; Rubio, Francisco; Salas, Eduardo; Dávalos, Antoni; Montaner, Joan

2017-09-01

Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase. The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves. From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P <0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P =0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%. The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke. © 2017 American Heart Association, Inc.

MicroRNA-182 downregulates Wnt/β-catenin signaling, inhibits proliferation, and promotes apoptosis in human osteosarcoma cells by targeting HOXA9

PubMed Central

Zhang, Zi-Feng; Wang, Yong-Jian; Fan, Shao-Hua; Du, Shi-Xin; Li, Xue-Dong; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

2017-01-01

We investigated the mechanisms by which microRNA (miR)-182 promotes apoptosis and inhibits proliferation in human osteosarcoma (OS) cells. Levels of miR-182 and Homeobox A9 (HOXA9) expression were compared between human OS and normal cells. Subjects were divided into OS and normal groups. We analyzed the target relationship of miR-182 and Homeobox A9 (HOXA9). Cells were then assigned into blank, negative control, miR-182 mimics, miR-182 inhibitors, siRNA-HOXA9, or and miR-182 inhibitors + siRNA-HOXA9 groups. Cell function was assayed by CCK-8, flow cytometry and wound healing assay. Additionally, we analyzed OS tumor growth in a xenograft mouse model. Dual-luciferase reporter assays indicated miR-182 directly targets HOXA9. Reverse transcription quantitative PCR and western blotting revealed elevated expression of miR-182, WIF-1, BIM, and Bax, and reduced expression of HOXA9, Wnt, β-catenin, Survivin, Cyclin D1, c-Myc, Mcl-1, Bcl-xL, and Snail in osteosarcoma cells treated with miR-182 mimic or siRNA-HOXA9 as compared to controls. Osteosarcoma cells also exhibited decreased cell proliferation, migration, and tumor growth, and increased apoptosis when treated with miR-182 mimic or siRNA-HOXA9. Correspondingly, in a xenograft mouse model, osteosarcoma tumor volume and growth were increased when cells were treated with miR-182 inhibitor and decreased by miR-182 mimic or siRNA-HOXA9. These results indicate that miR-182 downregulates Wnt/β-catenin signaling, inhibits cell proliferation, and promotes apoptosis in osteosarcoma cells by suppressing HOXA9 expression. PMID:29254169

A Computational Investigation of Small-Molecule Engagement of Hot Spots at Protein-Protein Interaction Interfaces.

PubMed

Xu, David; Si, Yubing; Meroueh, Samy O

2017-09-25

The binding affinity of a protein-protein interaction is concentrated at amino acids known as hot spots. It has been suggested that small molecules disrupt protein-protein interactions by either (i) engaging receptor protein hot spots or (ii) mimicking hot spots of the protein ligand. Yet, no systematic studies have been done to explore how effectively existing small-molecule protein-protein interaction inhibitors mimic or engage hot spots at protein interfaces. Here, we employ explicit-solvent molecular dynamics simulations and end-point MM-GBSA free energy calculations to explore this question. We select 36 compounds for which high-quality binding affinity and cocrystal structures are available. Five complexes that belong to three classes of protein-protein interactions (primary, secondary, and tertiary) were considered, namely, BRD4•H4, XIAP•Smac, MDM2•p53, Bcl-xL•Bak, and IL-2•IL-2Rα. Computational alanine scanning using MM-GBSA identified hot-spot residues at the interface of these protein interactions. Decomposition energies compared the interaction of small molecules with individual receptor hot spots to those of the native protein ligand. Pharmacophore analysis was used to investigate how effectively small molecules mimic the position of hot spots of the protein ligand. Finally, we study whether small molecules mimic the effects of the native protein ligand on the receptor dynamics. Our results show that, in general, existing small-molecule inhibitors of protein-protein interactions do not optimally mimic protein-ligand hot spots, nor do they effectively engage protein receptor hot spots. The more effective use of hot spots in future drug design efforts may result in smaller compounds with higher ligand efficiencies that may lead to greater success in clinical trials.

The Effect of Single and Double Acetylation of Lysine Residues on Structural and Dynamical Features of Human Splicing Factor TDP-43 - A Statistical Ensemble Analysis.

PubMed

Makhouri, Farahnaz Rezaei; Ghasemi, Jahan B

2018-06-04

The acetylated inclusions containing TDP-43 are found in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, suggesting that aberrant TDP-43 acetylation and resulting disruption of RNA binding are linked to onset and progression of TDP-43 proteinopathy. Here, the consequences of TDP-43 acetylation at Lys145 within the RRM1 domain and Lys192 within the RRM2 domain were studied using experimentally verifiable molecular models, in which lysine residues (K) were substituted with glutamine (Q) as an acetylation mimic (K→Q) and with arginine (R) as a non-mimic (K→R) mutant. We used a series of computer simulations to characterize the impact of lysine acetylation on TDP-43 function and TDP-43 association with target RNA. Using snapshots collected from the MD simulation trajectories, the cross-correlation and principal component analyses (PCA) were applied to shed light on the dynamic discrepancy among the ten studied systems and to discern TDP-43 subdomains that exhibit conformational plasticity in response to acetylation mimic and non-mimic mutations. Moreover, we also investigated the global network parameter, betweenness, to model communication pathways and identify a network of critical mediating nodes involved in long-range signaling. These nodes describe the functionally significant TDP-43 residues involved in TDP-43 regulation. The identification of the critical nodes and optimal path mediating the dynamical network communication could offer new strategies to manipulate TDP-43 function. Disrupting a specific network communication could represent a rational approach to the design of drugs with improved potency and selectivity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design, development and clinical validation of computer-aided surgical simulation system for streamlined orthognathic surgical planning.

PubMed

Yuan, Peng; Mai, Huaming; Li, Jianfu; Ho, Dennis Chun-Yu; Lai, Yingying; Liu, Siting; Kim, Daeseung; Xiong, Zixiang; Alfi, David M; Teichgraeber, John F; Gateno, Jaime; Xia, James J

2017-12-01

There are many proven problems associated with traditional surgical planning methods for orthognathic surgery. To address these problems, we developed a computer-aided surgical simulation (CASS) system, the AnatomicAligner, to plan orthognathic surgery following our streamlined clinical protocol. The system includes six modules: image segmentation and three-dimensional (3D) reconstruction, registration and reorientation of models to neutral head posture, 3D cephalometric analysis, virtual osteotomy, surgical simulation, and surgical splint generation. The accuracy of the system was validated in a stepwise fashion: first to evaluate the accuracy of AnatomicAligner using 30 sets of patient data, then to evaluate the fitting of splints generated by AnatomicAligner using 10 sets of patient data. The industrial gold standard system, Mimics, was used as the reference. When comparing the results of segmentation, virtual osteotomy and transformation achieved with AnatomicAligner to the ones achieved with Mimics, the absolute deviation between the two systems was clinically insignificant. The average surface deviation between the two models after 3D model reconstruction in AnatomicAligner and Mimics was 0.3 mm with a standard deviation (SD) of 0.03 mm. All the average surface deviations between the two models after virtual osteotomy and transformations were smaller than 0.01 mm with a SD of 0.01 mm. In addition, the fitting of splints generated by AnatomicAligner was at least as good as the ones generated by Mimics. We successfully developed a CASS system, the AnatomicAligner, for planning orthognathic surgery following the streamlined planning protocol. The system has been proven accurate. AnatomicAligner will soon be available freely to the boarder clinical and research communities.

On the success of a swindle: pollination by deception in orchids

NASA Astrophysics Data System (ADS)

Schiestl, Florian P.

2005-06-01

A standing enigma in pollination ecology is the evolution of pollinator attraction without offering reward in about one third of all orchid species. Here I review concepts of pollination by deception, and in particular recent findings in the pollination syndromes of food deception and sexual deception in orchids. Deceptive orchids mimic floral signals of rewarding plants (food deception) or mating signals of receptive females (sexual deception) to attract pollen vectors. In some food deceptive orchids, similarities in the spectral reflectance visible to the pollinator in a model plant and its mimic, and increased reproductive success of the mimic in the presence of the model have been demonstrated. Other species do not mimic specific model plants but attract pollinators with general attractive floral signals. In sexually deceptive orchids, floral odor is the key trait for pollinator attraction, and behaviorally active compounds in the orchids are identical to the sex pheromone of the pollinator species. Deceptive orchids often show high variability in floral signals, which may be maintained by negative frequency-dependent selection, since pollinators can learn and subsequently avoid common deceptive morphs more quickly than rare ones. The evolution of obligate deception in orchids seems paradoxical in the light of the typically lower fruit set than in rewarding species. Pollination by deception, however, can reduce self-pollination and encourage pollen flow over longer distances, thus promoting outbreeding. Although some food deceptive orchids are isolated through postzygotic reproductive barriers, sexually deceptive orchids lack post-mating barriers and species isolation is achieved via specific pollinator attraction. Recent population genetic and phylogenetic investigations suggest gene-flow within subgeneric clades, but pollinator-mediated selection may maintain species-specific floral traits.

A hypothesis to explain accuracy of wasp resemblances.

PubMed

Boppré, Michael; Vane-Wright, Richard I; Wickler, Wolfgang

2017-01-01

Mimicry is one of the oldest concepts in biology, but it still presents many puzzles and continues to be widely debated. Simulation of wasps with a yellow-black abdominal pattern by other insects (commonly called "wasp mimicry") is traditionally considered a case of resemblance of unprofitable by profitable prey causing educated predators to avoid models and mimics to the advantage of both (Figure 1a). However, as wasps themselves are predators of insects, wasp mimicry can also be seen as a case of resemblance to one's own potential antagonist. We here propose an additional hypothesis to Batesian and Müllerian mimicry (both typically involving selection by learning vertebrate predators; cf. Table 1) that reflects another possible scenario for the evolution of multifold and in particular very accurate resemblances to wasps: an innate, visual inhibition of aggression among look-alike wasps, based on their social organization and high abundance. We argue that wasp species resembling each other need not only be Müllerian mutualists and that other insects resembling wasps need not only be Batesian mimics, but an innate ability of wasps to recognize each other during hunting is the driver in the evolution of a distinct kind of masquerade, in which model, mimic, and selecting agent belong to one or several species (Figure  1b). Wasp mimics resemble wasps not (only) to be mistaken by educated predators but rather, or in addition, to escape attack from their wasp models. Within a given ecosystem, there will be selection pressures leading to masquerade driven by wasps and/or to mimicry driven by other predators that have to learn to avoid them. Different pressures by guilds of these two types of selective agents could explain the widely differing fidelity with respect to the models in assemblages of yellow jackets and yellow jacket look-alikes.

Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo

PubMed Central

Morelli, E; Leone, E; Cantafio, M E Gallo; Di Martino, M T; Amodio, N; Biamonte, L; Gullà, A; Foresta, U; Pitari, M R; Botta, C; Rossi, M; Neri, A; Munshi, N C; Anderson, K C; Tagliaferri, P; Tassone, P

2015-01-01

Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-MM activity of miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced significant anti-tumor activity and prolonged survival. Taken together, our findings provide evidence that miR-125b, differently from other hematologic malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents to be validated in early clinical trials. PMID:25987254

Insight into the role of Mg2+ in hammerhead ribozyme catalysis from X-ray crystallography and molecular dynamics simulation

PubMed Central

Lee, Tai-Sung; López, Carlos Silva; Martick, Monika; Scott, William G.; York, Darrin M.

2008-01-01

Results of a series of 12 ns molecular dynamics (MD) simulations of the reactant state (with and without a Mg2+ ion), early and late transition state mimics are presented based on a recently reported crystal structure of a full-length hammerhead RNA. The simulation results support a catalytically active conformation with a Mg2+ ion bridging the A9 and scissile phosphates. In the reactant state, the Mg2+ spends significant time closely associated with the 2′OH of G8, but remains fairly distant from the leaving group O5′ position. In the early TS mimic simulation, where the nucleophilic O2′ and leaving group O5′ are equidistant from the phosphorus, the Mg2+ ion remains tightly coordinated to the 2′OH of G8, but is positioned closer to the O5′ leaving group, stabilizing the accumulating charge. In the late TS mimic simulation, the coordination around the bridging Mg2+ ion undergoes a transition whereby the coordination with the 2′OH of G8 is replace by the leaving group O5′ that has developed significant charge. At the same time, the 2′OH of G8 forms a hydrogen bond with the leaving group O5′ and is positioned to act as a general acid catalyst. This work represents the first reported simulations of the full-length hammerhead structure and TS mimics, and provides direct evidence for the possible role of a bridging Mg2+ ion in catalysis that is consistent with both crystallographic and biochemical data. PMID:19079784

Design, development and clinical validation of computer-aided surgical simulation system for streamlined orthognathic surgical planning

PubMed Central

Yuan, Peng; Mai, Huaming; Li, Jianfu; Ho, Dennis Chun-Yu; Lai, Yingying; Liu, Siting; Kim, Daeseung; Xiong, Zixiang; Alfi, David M.; Teichgraeber, John F.; Gateno, Jaime

2017-01-01

Purpose There are many proven problems associated with traditional surgical planning methods for orthognathic surgery. To address these problems, we developed a computer-aided surgical simulation (CASS) system, the AnatomicAligner, to plan orthognathic surgery following our streamlined clinical protocol. Methods The system includes six modules: image segmentation and three-dimensional (3D) reconstruction, registration and reorientation of models to neutral head posture, 3D cephalometric analysis, virtual osteotomy, surgical simulation, and surgical splint generation. The accuracy of the system was validated in a stepwise fashion: first to evaluate the accuracy of AnatomicAligner using 30 sets of patient data, then to evaluate the fitting of splints generated by AnatomicAligner using 10 sets of patient data. The industrial gold standard system, Mimics, was used as the reference. Result When comparing the results of segmentation, virtual osteotomy and transformation achieved with AnatomicAligner to the ones achieved with Mimics, the absolute deviation between the two systems was clinically insignificant. The average surface deviation between the two models after 3D model reconstruction in AnatomicAligner and Mimics was 0.3 mm with a standard deviation (SD) of 0.03 mm. All the average surface deviations between the two models after virtual osteotomy and transformations were smaller than 0.01 mm with a SD of 0.01 mm. In addition, the fitting of splints generated by AnatomicAligner was at least as good as the ones generated by Mimics. Conclusion We successfully developed a CASS system, the AnatomicAligner, for planning orthognathic surgery following the streamlined planning protocol. The system has been proven accurate. AnatomicAligner will soon be available freely to the boarder clinical and research communities. PMID:28432489

In Vivo Evaluation of Lung Microwave Ablation in a Porcine Tumor Mimic Model

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

Planche, Olivier, E-mail: oli.hrp@gmail.com; Teriitehau, Christophe; Boudabous, Sana

2013-02-15

To evaluate the microwave ablation of created tumor mimics in the lung of a large animal model (pigs), with examination of the ablative synergy of multiple antennas. Fifty-six tumor-mimic models of various sizes were created in 15 pigs by using barium-enriched minced collected thigh muscle injected into the lung of the same animal. Tumors were ablated under fluoroscopic guidance by single-antenna and multiple-antenna microwaves. Thirty-five tumor models were treated in 11 pigs with a single antenna at 75 W for 15 min, with 15 measuring 20 mm in diameter, 10 measuring 30 mm, and 10 measuring 40 mm. Mean circularitymore » of the single-antenna ablation zones measured 0.64 {+-} 0.12, with a diameter of 35.7 {+-} 8.7 mm along the axis of the antenna and 32.7 {+-} 12.8 mm perpendicular to the feeding point. Multiple-antenna delivery of 75 W for 15 min caused intraprocedural death of 2 animals; modified protocol to 60 W for 10 min resulted in an ablation zone with a diameter of 43.0 {+-} 7.7 along the axis of the antenna and 54.8 {+-} 8.5 mm perpendicular to the feeding point; circularity was 0.70 {+-} 0.10. A single microwave antenna can create ablation zones large enough to cover lung tumor mimic models of {<=}4 cm with no heat sink effect from vessels of {<=}6 mm. Synergic use of 3 antennas allows ablation of larger volumes than single-antenna or radiofrequency ablation, but great caution must be taken when 3 antennas are used simultaneously in the lung in clinical practice.« less

Mucous retention cyst of temporal bone: a mimic of cholesteatoma on DW-MRI.

PubMed

Karandikar, Amit; Goh, Julian; Loke, Siu Cheng; Yeo, Seng Beng; Tan, Tiong Yong

2013-01-01

Non-EPI DW imaging is increasingly being used as a sensitive sequence in detecting cholesteatomas especially if CT findings are not confirmatory. Cholesteatoma appears as a hyperintense focus on DWI. We present two cases of mucous retention cysts in the mastoid temporal bone/middle ear cavity, which present as hyperintense on non-EPI DWI and potentially may mimic cholesteatomas. Differentiating between the two conditions is important, as surgery can be avoided in mucous retention cysts. We have also discussed ways to differentiate between these two conditions on MRI. To our knowledge, this entity is not reported previously. © 2013 Elsevier Inc. All rights reserved.

Nanofabricated Collagen-Inspired Synthetic Elastomers for Primary Rat Hepatocyte Culture

PubMed Central

Bettinger, Christopher J.; Kulig, Katherine M.; Vacanti, Joseph P.

2009-01-01

Synthetic substrates that mimic the properties of extracellular matrix proteins hold significant promise for use in systems designed for tissue engineering applications. In this report, we designed a synthetic polymeric substrate that is intended to mimic chemical, mechanical, and topological characteristics of collagen. We found that elastomeric poly(ester amide) substrates modified with replica-molded nanotopographic features enhanced initial attachment, spreading, and adhesion of primary rat hepatocytes. Further, hepatocytes cultured on nanotopographic substrates also demonstrated reduced albumin secretion and urea synthesis, which is indicative of strongly adherent hepatocytes. These results suggest that these engineered substrates can function as synthetic collagen analogs for in vitro cell culture. PMID:18847357

Tissue-like phantoms

DOEpatents

Frangioni, John V.; De Grand, Alec M.

2007-10-30

The invention is based, in part, on the discovery that by combining certain components one can generate a tissue-like phantom that mimics any desired tissue, is simple and inexpensive to prepare, and is stable over many weeks or months. In addition, new multi-modal imaging objects (e.g., beads) can be inserted into the phantoms to mimic tissue pathologies, such as cancer, or merely to serve as calibration standards. These objects can be imaged using one, two, or more (e.g., four) different imaging modalities (e.g., x-ray computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and near-infrared (NIR) fluorescence) simultaneously.

Race-Related Cognitive Test Bias in the ACTIVE Study: A MIMIC Model Approach

PubMed Central

Aiken Morgan, Adrienne T.; Marsiske, Michael; Dzierzewski, Joseph; Jones, Richard N.; Whitfield, Keith E.; Johnson, Kathy E.; Cresci, Mary K.

2010-01-01

The present study investigated evidence for race-related test bias in cognitive measures used in the baseline assessment of the ACTIVE clinical trial. Test bias against African Americans has been documented in both cognitive aging and early lifespan studies. Despite significant mean performance differences, Multiple Indicators Multiple Causes (MIMIC) models suggested most differences were at the construct level. There was little evidence that specific measures put either group at particular advantage or disadvantage and little evidence of cognitive test bias in this sample. Small group differences in education, cognitive status, and health suggest positive selection may have attenuated possible biases. PMID:20845121

Asthma mimic: Case report and literature review of vocal cord nodule associated with wheezing.

PubMed

Kashif, Muhammad; Singh, Tushi; Aslam, Ahsan; Khaja, Misbahuddin

2017-01-01

Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. Various clinical conditions can mimic asthma, such as foreign body aspiration, subglottic stenosis, congestive heart failure, diffuse panbronchiolitis, aortic arch anomalies, reactive airway dysfunction syndrome, chronic obstructive pulmonary disease, retrosternal goiter, vocal cord tumors, other airway tumors, and vocal cord dysfunction. Upper airway obstruction can be a life-threatening emergency. Here, we present the case of a 58-year-old female with recurrent hospital visits for wheezing and exacerbations of asthma, who was later found to have a vocal cord nodule confirmed to be squamous cell carcinoma, which was mimicking like asthma.

TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

PubMed

Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

2010-06-15

We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

Aberrant Anatomical Variation of Maxillary Sinus Mimicking Periapical Cyst: A Report of Two Cases and Role of CBCT in Diagnosis

PubMed Central

Sekerci, Ahmet Ercan; Sisman, Yildiray; Etoz, Meryem; Bulut, Duygu Goller

2013-01-01

Most periapical lesions are associated with microorganisms from infected root canal systems. Maxillary sinus can pose a diagnostic dilemma radiographically because of its anatomical variation which can mimic a periapical pathosis. The aim of this study was to describe two cases of aberrant anatomical variation of the maxillary sinus that presented radiographic similarities to a periapical cyst in order to call the attention of clinicians to the fact that several different diseases are able to mimic endodontic periapical lesions. An accurate assessment of this morphology was made with the help of cone-beam computed tomography (CBCT). PMID:23710374

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

PubMed Central

2008-01-01

Polyguanidinium oxanorbornene (PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents. PMID:18850741

An update on the Application of Nanotechnology in Bone Tissue Engineering.

PubMed

Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

2016-01-01

Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Coral settlement onto Halimeda opuntia: a fatal attraction to an ephemeral substrate?

NASA Astrophysics Data System (ADS)

Nugues, Maggy M.; Szmant, Alina M.

2006-11-01

Degraded reefs with a high abundance of macroalgae usually also have low densities of coral recruits. Few studies, however, have examined whether these algae affect coral larval settlement. This study demonstrates, experimentally, that larvae of the Caribbean coral Favia fragrum can settle on the green alga Halimeda opuntia even when another substrate more suitable for settlement is present. Larval settlement onto experimental substrates was quantified under three treatments: rubble only, rubble plus plastic algal mimic, and rubble plus live H. opuntia. Similar total larval settlement was observed in all treatments. No larvae settled on the algal mimic, but total settlement was similar on the rubble in the first two treatments, showing that the rubble alone offered sufficient substrate for high settlement success. About half the larvae in the live algal treatment settled on H. opuntia instead of on the rubble, showing that larvae did not reject this substrate as they did the algal mimic. This result raises the possibility that corals will settle on some macroalgae when their abundance is high. Most macroalgae, including H. opuntia, are ephemeral substrates unsuitable for post-settlement survival. Such unexpected settlement may therefore have significant consequences for coral recruitment success on algal-dominated reefs.

Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras

PubMed Central

Bianchini, Julie M.; Kitt, Khameeka N.; Gloerich, Martijn; Pokutta, Sabine; Weis, William I.

2015-01-01

As part of the E-cadherin–β-catenin–αE-catenin complex (CCC), mammalian αE-catenin binds F-actin weakly in the absence of force, whereas cytosolic αE-catenin forms a homodimer that interacts more strongly with F-actin. It has been concluded that cytosolic αE-catenin homodimer is not important for intercellular adhesion because E-cadherin/αE-catenin chimeras thought to mimic the CCC are sufficient to induce cell–cell adhesion. We show that, unlike αE-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly, and inhibit the Arp2/3 complex, all of which are properties of the αE-catenin homodimer. To more accurately mimic the junctional CCC, we designed a constitutively monomeric chimera, and show that E-cadherin–dependent cell adhesion is weaker in cells expressing this chimera compared with cells in which αE-catenin homodimers are present. Our results demonstrate that E-cadherin/αE-catenin chimeras used previously do not mimic αE-catenin in the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer αE-catenin are required for strong cell–cell adhesion. PMID:26416960

Solid tissue simulating phantoms having absorption at 970 nm for diffuse optics

NASA Astrophysics Data System (ADS)

Kennedy, Gordon T.; Lentsch, Griffin R.; Trieu, Brandon; Ponticorvo, Adrien; Saager, Rolf B.; Durkin, Anthony J.

2017-07-01

Tissue simulating phantoms can provide a valuable platform for quantitative evaluation of the performance of diffuse optical devices. While solid phantoms have been developed for applications related to characterizing exogenous fluorescence and intrinsic chromophores such as hemoglobin and melanin, we report the development of a poly(dimethylsiloxane) (PDMS) tissue phantom that mimics the spectral characteristics of tissue water. We have developed these phantoms to mimic different water fractions in tissue, with the purpose of testing new devices within the context of clinical applications such as burn wound triage. Compared to liquid phantoms, cured PDMS phantoms are easier to transport and use and have a longer usable life than gelatin-based phantoms. As silicone is hydrophobic, 9606 dye was used to mimic the optical absorption feature of water in the vicinity of 970 nm. Scattering properties are determined by adding titanium dioxide, which yields a wavelength-dependent scattering coefficient similar to that observed in tissue in the near-infrared. Phantom properties were characterized and validated using the techniques of inverse adding-doubling and spatial frequency domain imaging. Results presented here demonstrate that we can fabricate solid phantoms that can be used to simulate different water fractions.

Assassin bug uses aggressive mimicry to lure spider prey.

PubMed

Wignall, Anne E; Taylor, Phillip W

2011-05-07

Assassin bugs (Stenolemus bituberus) hunt web-building spiders by invading the web and plucking the silk to generate vibrations that lure the resident spider into striking range. To test whether vibrations generated by bugs aggressively mimic the vibrations generated by insect prey, we compared the responses of spiders to bugs with how they responded to prey, courting male spiders and leaves falling into the web. We also analysed the associated vibrations. Similar spider orientation and approach behaviours were observed in response to vibrations from bugs and prey, whereas different behaviours were observed in response to vibrations from male spiders and leaves. Peak frequency and duration of vibrations generated by bugs were similar to those generated by prey and courting males. Further, vibrations from bugs had a temporal structure and amplitude that were similar to vibrations generated by leg and body movements of prey and distinctly different to vibrations from courting males or leaves, or prey beating their wings. To be an effective predator, bugs do not need to mimic the full range of prey vibrations. Instead bugs are general mimics of a subset of prey vibrations that fall within the range of vibrations classified by spiders as 'prey'.

Single-Walled Carbon Nanotubes: Mimics of Biological Ion Channels.

PubMed

Amiri, Hasti; Shepard, Kenneth L; Nuckolls, Colin; Hernández Sánchez, Raúl

2017-02-08

Here we report on the ion conductance through individual, small diameter single-walled carbon nanotubes. We find that they are mimics of ion channels found in natural systems. We explore the factors governing the ion selectivity and permeation through single-walled carbon nanotubes by considering an electrostatic mechanism built around a simplified version of the Gouy-Chapman theory. We find that the single-walled carbon nanotubes preferentially transported cations and that the cation permeability is size-dependent. The ionic conductance increases as the absolute hydration enthalpy decreases for monovalent cations with similar solid-state radii, hydrated radii, and bulk mobility. Charge screening experiments using either the addition of cationic or anionic polymers, divalent metal cations, or changes in pH reveal the enormous impact of the negatively charged carboxylates at the entrance of the single-walled carbon nanotubes. These observations were modeled in the low-to-medium concentration range (0.1-2.0 M) by an electrostatic mechanism that mimics the behavior observed in many biological ion channel-forming proteins. Moreover, multi-ion conduction in the high concentration range (>2.0 M) further reinforces the similarity between single-walled carbon nanotubes and protein ion channels.

A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone

PubMed Central

Pruitt, Rory N.; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R.; Ronald, Pamela C.

2018-01-01

Summary The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides.Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides.Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence.These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. PMID:28556915

Identification of measurement differences between English and Spanish language versions of the Mini-Mental State Examination. Detecting differential item functioning using MIMIC modeling.

PubMed

Jones, Richard N

2006-11-01

Knowledge of the extent to which measurement of adult cognitive functioning differs between Spanish and English language administrations of the Mini-Mental State Examination (MMSE) is critical for inclusive, representative, and valid research of older adults in the United States. We sought to demonstrate the use of an item response theory (IRT) based structural equation model, that is, the MIMIC model (multiple indicators, multiple causes), to evaluate MMSE responses for evidence of differential item functioning (DIF) attributable to language of administration. We studied participants in a dementia case registry study (n = 1546), 42% of whom were examined with the Spanish language MMSE. Twelve of 21 items were identified as having significant uniform DIF. The 4 most discrepant included orientation to season, orientation to state, repeat phrase, and follow command. DIF accounted for two-thirds of the observed difference in underlying level of cognitive functioning between Spanish- and English-language administration groups. Failing to account for measurement differences may lead to spurious inferences regarding language group differences in level of underlying level of cognitive functioning. The MIMIC model can be used to detect and adjust for such measurement differences in substantive research.

Deuterohemin-Peptide Enzyme Mimic-Embedded Metal-Organic Frameworks through Biomimetic Mineralization with Efficient ATRP Catalytic Activity.

PubMed

Jiang, Wei; Wang, Xinghuo; Chen, Jiawen; Liu, Ying; Han, Haobo; Ding, Yi; Li, Quanshun; Tang, Jun

2017-08-16

An enzyme mimic harboring iron porphyrin (DhHP-6) embedded in zeolite imidazolate framework-8 (ZIF-8) was constructed through a biomimetic mineralization approach to obtain composite DhHP-6@ZIF-8. The composite was then used as a catalyst in the atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA 500 ) in which poly(PEGMA 500 ) could be synthesized with monomer conversion of 76.1% and M n of 45 900 g/mol, stronger than that obtained when using free DhHP-6 as a catalyst. More importantly, it could efficiently overcome the drawbacks of free DhHP-6 and achieve the easy separation of DhHP-6 from the catalytic system and the elimination of iron residues in the synthesized polymer. In addition, it exhibited an enhanced recyclability with monomer conversion of 75.7% after five cycles and favorable stability during the ATRP reaction with <3.0% of DhHP-6 release within 100 h. Thus, the enzyme mimic-ZIF-8 composite developed through biomimetic mineralization can be potentially used as an effective catalyst for preparing well-defined polymers with biomedical applications.

Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

NASA Astrophysics Data System (ADS)

Feng, Mei; Bell, David R.; Zhou, Ruhong

2017-12-01

The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

PubMed Central

Marrakchi, S.; Kammoun, I.; Kachboura, S.

2014-01-01

Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope. PMID:25114686

Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.

PubMed

Celic, T; Španjol, J; Bobinac, M; Tovmasyan, A; Vukelic, I; Reboucas, J S; Batinic-Haberle, I; Bobinac, D

2014-12-01

Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP(3-)), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP(3-) was not. Here, for the first time, in a complex in vivo system-animal model of spinal cord injury-a similar impact of MnTBAP(3-), at a dose identical to that of MnTnHex-2-PyP(5+), was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP(3-) with reactive nitrogen species (RNS) (.NO/HNO/ONOO(-)) suggests that RNS/MnTBAP(3-)-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP(5+) which presumably occurs via reactive oxygen species and relates to NF-κB thiol oxidation; the role of RNS cannot be excluded.

Insight into the structure and mechanism of nickel-containing superoxide dismutase derived from peptide-based mimics.

PubMed

Shearer, Jason

2014-08-19

Nickel superoxide dismutase (NiSOD) is a nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide through a ping-pong mechanism that relies on accessing reduced Ni(II) and oxidized Ni(III) oxidation states. NiSOD is the most recently discovered SOD. Unlike the other known SODs (MnSOD, FeSOD, and (CuZn)SOD), which utilize "typical" biological nitrogen and oxygen donors, NiSOD utilizes a rather unexpected ligand set. In the reduced Ni(II) oxidation state, NiSOD utilizes nitrogen ligands derived from the N-terminal amine and an amidate along with two cysteinates sulfur donors. These are unusual biological ligands, especially for an SOD: amine and amidate donors are underrepresented as biological ligands, whereas cysteinates are highly susceptible to oxidative damage. An axial histidine imidazole binds to nickel upon oxidation to Ni(III). This bond is long (2.3-2.6 Å) owing to a tight hydrogen-bonding network. All of the ligating residues to Ni(II) and Ni(III) are found within the first 6 residues from the NiSOD N-terminus. Thus, small nickel-containing metallopeptides derived from the first 6-12 residues of the NiSOD sequence can reproduce many of the properties of NiSOD itself. Using these nickel-containing metallopeptide-based NiSOD mimics, we have shown that the minimal sequence needed for nickel binding and reproduction of the structural, spectroscopic, and functional properties of NiSOD is H2N-HCXXPC. Insight into how NiSOD avoids oxidative damage has also been gained. Using small NiN2S2 complexes and metallopeptide-based mimics, it was shown that the unusual nitrogen donor atoms protect the cysteinates from oxidative damage (both one-electron oxidation and oxygen atom insertion reactions) by fine-tuning the electronic structure of the nickel center. Changing the nitrogen donor set to a bis-amidate or bis-amine nitrogen donor led to catalytically nonviable species owing to nickel-cysteinate bond oxidative damage. Only the amine/amidate nitrogen donor atoms within the NiSOD ligand set produce a catalytically viable species. These metallopeptide-based mimics have also hinted at the detailed mechanism of SOD catalysis by NiSOD. One such aspect is that the axial imidazole likely remains ligated to the Ni center under rapid catalytic conditions (i.e., high superoxide loads). This reduces the degree of structural rearrangement about the nickel center, leading to higher catalytic rates. Metallopeptide-based mimics have also shown that, although an axial ligand to Ni(III) is required for catalysis, the rates are highest when this is a weak interaction, suggesting a reason for the long axial His-Ni(III) bond found in NiSOD. These mimics have also suggested a surprising mechanistic insight: O2(-) reduction via a "H(•)" tunneling event from a R-S(H(+))-Ni(II) moiety to O2(-) is possible. The importance of this mechanism in NiSOD has not been verified.

miR-34: from bench to bedside

PubMed Central

Agostini, Massimiliano; Knight, Richard A.

2014-01-01

The mir-34 family was originally cloned and characterized in 2007 as a p53 target gene. Almost immediately it became clear that its major role is as a master regulator of tumor suppression. Indeed, when overexpressed, it directly and indirectly represses several oncogenes, resulting in an increase of cancer cell death (including cancer stem cells), and in an inhibition of metastasis. Moreover, its expression is deregulated in several human cancers. In 2013, a miR-34 mimic has become the first microRNA to reach phase 1 clinical trials. Here we review the miR-34 family and their role in tumor biology, and discuss the potential therapeutic applications of miR-34a mimic. PMID:24657911

A self-resetting spiking phase-change neuron

NASA Astrophysics Data System (ADS)

Cobley, R. A.; Hayat, H.; Wright, C. D.

2018-05-01

Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities. Such phase-change neurons, in combination with phase-change synapses, can potentially open a new route for the realisation of all-phase-change neuromorphic computing.

How effectively does a clinostat mimic the ultrastructural effects of microgravity on plant cells?

NASA Technical Reports Server (NTRS)

Moore, R.

1990-01-01

Columella cells of seedlings of Zea mays L. cv. Bear Hybrid grown in the microgravity of orbital flight allocate significantly larger relative-volumes to hyaloplasm and lipid bodies, and significantly smaller relative-volumes to dictyosomes, plastids, and starch than do columella cells of seedlings grown at 1 g. The ultrastructure of columella cells of seedlings grown at 1 g and on a rotating clinostat is not significantly different. However, the ultrastructure of cells exposed to these treatments differs significantly from that of seedlings grown in microgravity. These results indicate that the actions of a rotating clinostat do not mimic the ultrastructural effects of microgravity in columella cells of Z. mays.

Magnetic Tunnel Junction Mimics Stochastic Cortical Spiking Neurons

NASA Astrophysics Data System (ADS)

Sengupta, Abhronil; Panda, Priyadarshini; Wijesinghe, Parami; Kim, Yusung; Roy, Kaushik

2016-07-01

Brain-inspired computing architectures attempt to mimic the computations performed in the neurons and the synapses in the human brain in order to achieve its efficiency in learning and cognitive tasks. In this work, we demonstrate the mapping of the probabilistic spiking nature of pyramidal neurons in the cortex to the stochastic switching behavior of a Magnetic Tunnel Junction in presence of thermal noise. We present results to illustrate the efficiency of neuromorphic systems based on such probabilistic neurons for pattern recognition tasks in presence of lateral inhibition and homeostasis. Such stochastic MTJ neurons can also potentially provide a direct mapping to the probabilistic computing elements in Belief Networks for performing regenerative tasks.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

PubMed

Uygun, Kazim; Kocak, Zafer; Altaner, Semsi; Cicin, Irfan; Tokatli, Fusun; Uzal, Cem

2006-08-31

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

A sensory origin for color-word stroop effects in aging: simulating age-related changes in color-vision mimics age-related changes in Stroop.

PubMed

Ben-David, Boaz M; Schneider, Bruce A

2010-11-01

An increase in Stroop effects with age can be interpreted as reflecting age-related reductions in selective attention, cognitive slowing, or color-vision. In the present study, 88 younger adults performed a Stroop test with two color-sets, saturated and desaturated, to simulate an age-related decrease in color perception. This color manipulation with younger adults was sufficient to lead to an increase in Stroop effects that mimics age-effects. We conclude that age-related changes in color perception can contribute to the differences in Stroop effects observed in aging. Finally, we suggest that the clinical applications of Stroop take this factor into account.

The effect of concentration in the patterning of silica particles by the soft lithographic technique

NASA Astrophysics Data System (ADS)

Singh, Akanksha; Malek, Chantal Khan; Kulkarni, Sulabha K.

2008-12-01

Soft lithography provides remarkable surface patterning techniques to organize colloidal particles for a wide variety of applications. In particular, micromolding in capillaries (MIMIC) has emerged as a patterning method in the nanometer to micrometer scale in a single step by using templating and directing nanoparticles via capillary forces in the channel. The present work reports the results of the micropatterning of monodispersed silica particles of ~338 ± 2 nm size in ethanol medium, using MIMIC on silicon substrates. The effect of the concentration of silica particles on the patterning has been investigated. The patterns are well aligned and completely filled at 2 wt% concentration of silica particles.

Post interaural neural net-based vowel recognition

NASA Astrophysics Data System (ADS)

Jouny, Ismail I.

2001-10-01

Interaural head related transfer functions are used to process speech signatures prior to neural net based recognition. Data representing the head related transfer function of a dummy has been collected at MIT and made available on the Internet. This data is used to pre-process vowel signatures to mimic the effects of human ear on speech perception. Signatures representing various vowels of the English language are then presented to a multi-layer perceptron trained using the back propagation algorithm for recognition purposes. The focus in this paper is to assess the effects of human interaural system on vowel recognition performance particularly when using a classification system that mimics the human brain such as a neural net.

Moving like a model: mimicry of hymenopteran flight trajectories by clearwing moths of Southeast Asian rainforests.

PubMed

Skowron Volponi, Marta A; McLean, Donald James; Volponi, Paolo; Dudley, Robert

2018-05-01

Clearwing moths are known for their physical resemblance to hymenopterans, but the extent of their behavioural mimicry is unknown. We describe zigzag flights of sesiid bee mimics that are nearly indistinguishable from those of sympatric bees, whereas sesiid wasp mimics display faster, straighter flights more akin to those of wasps. In particular, the flight of the sesiids Heterosphecia pahangensis , Aschistophleps argentifasciata and Pyrophleps cruentata resembles both Tetragonilla collina and T. atripes stingless bees and, to a lesser extent, dwarf honeybees Apis andreniformis , whereas the sesiid Pyrophleps sp. resembles Tachysphex sp. wasps. These findings represent the first experimental evidence for behavioural mimicry in clearwing moths. © 2018 The Author(s).

A self-resetting spiking phase-change neuron.

PubMed

Cobley, R A; Hayat, H; Wright, C D

2018-05-11

Neuromorphic, or brain-inspired, computing applications of phase-change devices have to date concentrated primarily on the implementation of phase-change synapses. However, the so-called accumulation mode of operation inherent in phase-change materials and devices can also be used to mimic the integrative properties of a biological neuron. Here we demonstrate, using physical modelling of nanoscale devices and SPICE modelling of associated circuits, that a single phase-change memory cell integrated into a comparator type circuit can deliver a basic hardware mimic of an integrate-and-fire spiking neuron with self-resetting capabilities. Such phase-change neurons, in combination with phase-change synapses, can potentially open a new route for the realisation of all-phase-change neuromorphic computing.

Polyproline as a Minimal Antifreeze Protein Mimic That Enhances the Cryopreservation of Cell Monolayers

PubMed Central

Graham, Ben; Bailey, Trisha L.; Healey, Joseph R. J.; Marcellini, Moreno; Deville, Sylvain

2017-01-01

Abstract Tissue engineering, gene therapy, drug screening, and emerging regenerative medicine therapies are fundamentally reliant on high‐quality adherent cell culture, but current methods to cryopreserve cells in this format can give low cell yields and require large volumes of solvent “antifreezes”. Herein, we report polyproline as a minimum (bio)synthetic mimic of antifreeze proteins that is accessible by solution, solid‐phase, and recombinant methods. We demonstrate that polyproline has ice recrystallisation inhibition activity linked to its amphipathic helix and that it enhances the DMSO cryopreservation of adherent cell lines. Polyproline may be a versatile additive in the emerging field of macromolecular cryoprotectants. PMID:29044869

Polyproline as a Minimal Antifreeze Protein Mimic That Enhances the Cryopreservation of Cell Monolayers.

PubMed

Graham, Ben; Bailey, Trisha L; Healey, Joseph R J; Marcellini, Moreno; Deville, Sylvain; Gibson, Matthew I

2017-12-11

Tissue engineering, gene therapy, drug screening, and emerging regenerative medicine therapies are fundamentally reliant on high-quality adherent cell culture, but current methods to cryopreserve cells in this format can give low cell yields and require large volumes of solvent "antifreezes". Herein, we report polyproline as a minimum (bio)synthetic mimic of antifreeze proteins that is accessible by solution, solid-phase, and recombinant methods. We demonstrate that polyproline has ice recrystallisation inhibition activity linked to its amphipathic helix and that it enhances the DMSO cryopreservation of adherent cell lines. Polyproline may be a versatile additive in the emerging field of macromolecular cryoprotectants. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone.

PubMed

Pruitt, Rory N; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R; Ronald, Pamela C

2017-07-01

The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides. Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides. Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence. These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. © 2017 UT-Battelle LLC. New Phytologist © 2017 New Phytologist Trust.

A novel image processing technique for 3D volumetric analysis of severely resorbed alveolar sockets with CBCT.

PubMed

Manavella, Valeria; Romano, Federica; Garrone, Federica; Terzini, Mara; Bignardi, Cristina; Aimetti, Mario

2017-06-01

The aim of this study was to present and validate a novel procedure for the quantitative volumetric assessment of extraction sockets that combines cone-beam computed tomography (CBCT) and image processing techniques. The CBCT dataset of 9 severely resorbed extraction sockets was analyzed by means of two image processing software, Image J and Mimics, using manual and automated segmentation techniques. They were also applied on 5-mm spherical aluminum markers of known volume and on a polyvinyl chloride model of one alveolar socket scanned with Micro-CT to test the accuracy. Statistical differences in alveolar socket volume were found between the different methods of volumetric analysis (P<0.0001). The automated segmentation using Mimics was the most reliable and accurate method with a relative error of 1.5%, considerably smaller than the error of 7% and of 10% introduced by the manual method using Mimics and by the automated method using ImageJ. The currently proposed automated segmentation protocol for the three-dimensional rendering of alveolar sockets showed more accurate results, excellent inter-observer similarity and increased user friendliness. The clinical application of this method enables a three-dimensional evaluation of extraction socket healing after the reconstructive procedures and during the follow-up visits.

Nanoparticle delivery of miR-223 to attenuate macrophage fusion

PubMed Central

Moore, Laura Beth; Sawyer, Andrew J.; Saucier-Sawyer, Jennifer; Saltzman, W. Mark; Kyriakides, Themis R.

2016-01-01

The foreign body response (FBR) begins with injury acquired during implantation of a biomaterial (BM) and is detrimental due to the eventual encapsulation of the implant. Fusion of macrophages to form foreign body giant cells (FBGC), a hallmark of the FBR, is the consequence of a multistep mechanism induced by interleukin (IL)-4 that includes the acquisition of a fusion competent state and subsequent cytoskeletal rearrangements. However, the precise mechanism, regulation, and interplay among molecular mediators to generate FBGCs are insufficiently understood. Seeking novel mediators of fusion that might be regulated at the post-transcriptional level, we examined the role of microRNAs (miRs) in this process. A miR microarray was screened and identified miR-223 as a negative regulator of macrophage fusion. In addition, transfection of primary macrophages with a mir-223 mimic attenuated IL-4-induced fusion. Furthermore, miR-223 KO mice and mir-223 deficient cells displayed increased fusion in vivo and in vitro, respectively. Finally, we developed a method for in vivo delivery of miR-223 mimic utilizing PLGA nanoparticles, which inhibited FBGC formation in a biomaterial implant model. Our results identify miR-223 as a negative regulator of fusion and demonstrate miR-223 mimic-loaded nanoparticles as a therapeutic inhibitor of macrophage fusion. PMID:26967647

Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

PubMed Central

Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

2014-01-01

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

Nacre-mimic Reinforced Ag@reduced Graphene Oxide-Sodium Alginate Composite Film for Wound Healing.

PubMed

Yan, Xu; Li, Fei; Hu, Kang-Di; Xue, Jingzhe; Pan, Xiao-Feng; He, Tao; Dong, Liang; Wang, Xiang-Ying; Wu, Ya-Dong; Song, Yong-Hong; Xu, Wei-Ping; Lu, Yang

2017-10-23

With the emerging of drug-resistant bacterial and fungal pathogens, there raise the interest of utilizing versatile antimicrobial biomaterials to treat the acute wound. Herein, we report the spraying mediated assembly of a bio-inspired Ag@reduced graphene-sodium alginate (AGSA) composite film for effective wound healing. The obtained film displayed lamellar microstructures similar to the typical "brick-and-mortar" structure in nacre. In this nacre-mimic structure, there are abundant interfacial interactions between nanosheets and polymeric matrix, leading to remarkable reinforcement. As a result, the tensile strength, toughness and Young's modulus have been improved 2.8, 2.3 and 2.7 times compared with pure sodium alginate film, respectively. In the wound healing study, the AGSA film showed effective antimicrobial activities towards Pseudomonas aeruginosa, Escherichia coli and Candida albicans, demonstrating the ability of protecting wound from pathogenic microbial infections. Furthermore, in vivo experiments on rats suggested the effect of AGSA film in promoting the recovery of wound sites. According to MTT assays, heamolysis evaluation and in vivo toxicity assessment, the composite film could be applied as a bio-compatible material in vitro and in vivo. Results from this work indicated such AGSA film has promising performance for wound healing and suggested great potential for nacre-mimic biomaterials in tissue engineering applications.

A TNF receptor loop peptide mimic blocks RANK ligand–induced signaling, bone resorption, and bone loss

PubMed Central

Aoki, Kazuhiro; Saito, Hiroaki; Itzstein, Cecile; Ishiguro, Masaji; Shibata, Tatsuya; Blanque, Roland; Mian, Anower Hussain; Takahashi, Mariko; Suzuki, Yoshifumi; Yoshimatsu, Masako; Yamaguchi, Akira; Deprez, Pierre; Mollat, Patrick; Murali, Ramachandran; Ohya, Keiichi; Horne, William C.; Baron, Roland

2006-01-01

Activating receptor activator of NF-κB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-α–induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF–induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-α promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF. PMID:16680194

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia).

PubMed

Ortins-Pina, Ana; Llamas-Velasco, Mar; Turpin, Sara; Soares-de-Almeida, Luís; Filipe, Paulo; Kutzner, Heinz

2018-06-01

Accurate distinction of epithelioid hemangioma (EH) from its malignant mimics is paramount but remains challenging due to its wide morphological spectrum and lack of objective molecular markers. FOSB oncogenic activation was recently identified as a key event in endothelial proliferation. We sought to investigate the FOSB staining pattern in EH with angiolymphoid hyperplasia with eosinophilia (EH-AHLE) morphology and to evaluate its value in differential diagnosis of epithelioid vascular tumors. From the authors' files, 15 representative cases of EH-ALHE were selected and evaluated for their FOSB immunostaining pattern. Other vascular proliferations which can be morphological mimics were also tested: epithelioid hemangioendothelioma (EHE) (5 cases) and epithelioid angiosarcoma (EAS) (5 cases). All 15 cases of EH-ALHE showed strong and homogeneous FOSB nuclear expression in endothelial cells with ample cytoplasm and intracytoplasmic vacuoles. All cases of EHE and EAS lacked FOSB immunoreactivity or showed only incidental weak FOSB immunoreactivity in less than 5 nuclei per lesion. FOSB immunohistochemistry is sensitive in the diagnosis of EH-ALHE, and allows differentiation from its histological mimics. An immunohistochemical panel including not only pan-cytokeratin AE1/AE3 and endothelial markers, but also FOSB, helps in the diagnosis of epithelioid vascular tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ant mimicry lessens predation on a North American jumping spider by larger salticid spiders.

PubMed

Durkee, Caitlin A; Weiss, Martha R; Uma, Divya B

2011-10-01

Ant-like appearance (myrmecomorphy) has evolved >70 times in insects and spiders, accounting for >2,000 species of myrmecomorphic arthropods. Most myrmecomorphic spiders are considered to be Batesian mimics; that is, a palatable spider avoids predation through resemblance to an unpalatable ant-although this presumption has been tested in relatively few cases. Here we explicitly examined the extent to which Peckhamia picata (Salticidae), a North American ant-mimicking jumping spider, is protected from four species of jumping spider predators, relative to nonmimetic salticids and model ants. In addition, we conducted focused behavioral observations on one salticid predator, Thiodina puerpera, to determine the point at which the predators' behaviors toward model, mimic, and nonmimic diverge. We also examined the behaviors of Peckhamia in the presence of Thiodina. We found that mimetic jumping spiders were consumed less than a third as often as nonmimetic jumping spiders, suggesting that Peckhamia does indeed gain protection as a result of its resemblance to ants, and so can be considered a Batesian mimic. Furthermore, our focal predator did not consume any ant-mimicking spiders, and seemed to categorize Peckhamia with its model ant early in the hunting sequence. Such early determination of prey versus nonprey may be the result of speed-accuracy trade-offs in predator decision-making.

Neuronal responses to an asymmetrical alternating current field can mimic those produced by an imposed direct current field in vitro.

PubMed

Pan, Linjie; Cirillo, John; Borgens, Richard Ben

2012-08-01

The remarkable polarity-dependent growth and anatomical organization of neurons in vitro produced by imposed direct current (DC) voltage gradients (electrical fields; Ef) can be mimicked by another type of electrical cue. This is a properly structured asymmetrical alternating current (AC) electrical field (A-ACEf). Here we provide details on the construction of an AC signal generator in which all components of an AC waveform can be individually controlled. We show that 1) conventional symmetrical AC voltage gradients will not induce growth, guidance, or architectural changes in sympathetic neurons. We also provide the first qualitative and quantitative data showing that an asymmetric AC application can indeed mimic the DC response in chick sympathetic neurons and their growing neurites. This shift in orientation and neuronal anatomy requires dieback of some neurites and the extension of others to produce a preferred orientation perpendicular to the gradient of voltage. Our new results may lead to a noninvasive means to modify nerve growth and organization by magnetic inductive coupling at distance. These data also indicate the possibility of a means to mimic DC-dependent release of drugs or other biologically active molecules from electrically sensitive that can be loaded with these chemical cargos. Copyright © 2012 Wiley Periodicals, Inc.

Intravital Confocal and Two-photon Imaging of Dual-color Cells and Extracellular Matrix Mimics

PubMed Central

Bal, Ufuk; Andresen, Volker; Baggett, Brenda; Utzinger, Urs

2013-01-01

To optimize imaging of cells in three dimensional culture we studied confocal backscattering, Second Harmonic Generation (SHG) and autofluorescence as source of contrast in extracellular matrix (ECM) mimics and evaluated the attenuation as well as bleaching of endogenous cellular fluorescence signals. All common ECM mimics exhibit contrast observable with confocal reflectance microscopy. SHG imaging on collagen I based hydrogels provides high contrast and good optical penetration depth. Agarose is a useful embedding medium because it allows for large optical penetration and exhibits minimal autofluorescence while still providing good reflectance to detect voids in the embedding medium. We labeled breast cancer cells’ outline with DsRed2 and nucleus with eGFP. DsRed2 can be excited with confocal imaging at 568nm, and with two photon excitation (TPE) in the red and longer NIR. eGFP was excited at 488nm for confocal and in the NIR for TPE. While there is small difference in the bleaching rate for eGFP between confocal and TPE we observed significant difference for DsRed2 where bleaching is strongest during TPE in the red wavelengths and smallest during confocal imaging. After a few hundred microns depth in a collagen I hydrogel, TPE fluorescence becomes twice as strong compared to confocal imaging. PMID:23380006

Phosphoryl transfer reaction snapshots in crystals: Insights into the mechanism of protein kinase a catalytic subunit

DOE PAGES

Das, Amit; Gerlits, Oksana O.; Heller, William T.; ...

2015-06-19

To study the catalytic mechanism of phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) a structure of the enzyme-substrate complex representing the Michaelis complex is of specific interest as it can shed light on the structure of the transition state. However, all previous crystal structures of the Michaelis complex mimics of the PKA catalytic subunit (PKAc) were obtained with either peptide inhibitors or ATP analogs. Here we utilized Ca 2+ ions and sulfur in place of the nucleophilic oxygen in a 20-residue pseudo-substrate peptide (CP20) and ATP to produce a close mimic of the Michaelis complex. In the ternary reactant complex,more » the thiol group of Cys-21 of the peptide is facing Asp-166 and the sulfur atom is positioned for an in-line phosphoryl transfer. Replacement of Ca 2+ cations with Mg 2+ ions resulted in a complex with trapped products of ATP hydrolysis: phosphate ion and ADP. As a result, the present structural results in combination with the previously reported structures of the transition state mimic and phosphorylated product complexes complete the snapshots of the phosphoryl transfer reaction by PKAc, providing us with the most thorough picture of the catalytic mechanism to date.« less

Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche

PubMed Central

Aguado, Brian A.; Caffe, Jordan R.; Nanavati, Dhaval; Rao, Shreyas S.; Bushnell, Grace G.; Azarin, Samira M.; Shea, Lonnie D.

2016-01-01

Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. PMID:26844426

Novel β-amyloid aggregation inhibitors possessing a turn mimic.

PubMed

Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

2015-04-01

Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide.

PubMed

Matsubara, Teruhiko; Ujie, Michiko; Yamamoto, Takashi; Akahori, Miku; Einaga, Yasuaki; Sato, Toshinori

2016-08-09

The progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. Anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. Here, we show that several dozen plaque-forming units (pfu) of influenza virus (IFV) can be detected using a boron-doped diamond (BDD) electrode terminated with a sialic acid-mimic peptide. The peptide was used instead of the sialyloligosaccharide receptor, which is the common receptor of influenza A and B viruses required during the early phase of infection, to capture IFV particles. The peptide, which was previously identified by phage-display technology, was immobilized by click chemistry on the BDD electrode, which has excellent electrochemical characteristics such as low background current and weak adsorption of biomolecules. Electrochemical impedance spectroscopy revealed that H1N1 and H3N2 IFVs were detectable in the range of 20-500 pfu by using the peptide-terminated BDD electrode. Our results demonstrate that the BDD device integrated with the receptor-mimic peptide has high sensitivity for detection of a low number of virus particles in the early phase of infection.

Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

PubMed Central

Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

2015-01-01

Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. PMID:26304926

An orthosteric inhibitor of the RAS-SOS interaction.

PubMed

Nickerson, Seth; Joy, Stephen T; Arora, Paramjit S; Bar-Sagi, Dafna

2013-01-01

Rat sarcoma (RAS) proteins are signaling nodes that transduce extracellular cues into precise alterations in cellular physiology by engaging effector pathways. RAS signaling thus regulates diverse cell processes including proliferation, migration, differentiation, and survival. Owing to this central role in governing mitogenic signals, RAS pathway components are often dysregulated in human diseases. Targeted therapy of RAS pathways has generally not been successful, largely because of the robust biochemistry of the targets and their multifaceted network of molecular regulators. The rate-limiting step of RAS activation is Son of Sevenless (SOS)-mediated nucleotide exchange involving a single evolutionarily conserved catalytic helix from SOS. Structure function data of this mechanism provided a strong platform to design an SOS-derived, helically constrained peptide mimic as an inhibitor of the RAS-SOS interaction. In this chapter, we review RAS-SOS signaling dynamics and present evidence supporting the novel paradigm of inhibiting their interaction as a therapeutic strategy. We then describe a method of generating helically constrained peptide mimics of protein surfaces, which we have employed to inhibit the RAS-SOS active site interaction. The biochemical and functional properties of this SOS mimic support the premise that inhibition of RAS-nucleotide exchange can effectively block RAS activation and downstream signaling. © 2013 Elsevier Inc. All rights reserved.

HER-3 peptide vaccines/mimics: Combined therapy with IGF-1R, HER-2, and HER-1 peptides induces synergistic antitumor effects against breast and pancreatic cancer cells.

PubMed

Miller, Megan Jo; Foy, Kevin C; Overholser, Jay P; Nahta, Rita; Kaumaya, Pravin Tp

2014-11-01

The human epidermal growth factor receptor 3 (HER-3/ErbB3) is a unique member of the human epidermal growth factor family of receptors, because it lacks intrinsic kinase activity and ability to heterodimerize with other members. HER-3 is frequently upregulated in cancers with epidermal growth factor receptor (EGFR/HER-1/ErbB1) or human epidermal growth factor receptor 2 (HER-2/ErBB2) overexpression, and targeting HER-3 may provide a route for overcoming resistance to agents that target EGFR or HER-2. We have previously developed vaccines and peptide mimics for HER-1, HER-2 and vascular endothelial growth factor (VEGF). In this study, we extend our studies by identifying and evaluating novel HER-3 peptide epitopes encompassing residues 99-122, 140-162, 237-269 and 461-479 of the HER-3 extracellular domain as putative B-cell epitopes for active immunotherapy against HER-3 positive cancers. We show that the HER-3 vaccine antibodies and HER-3 peptide mimics induced antitumor responses: inhibition of cancer cell proliferation, inhibition of receptor phosphorylation, induction of apoptosis and antibody dependent cellular cytotoxicity (ADCC). Two of the HER-3 epitopes 237-269 (domain II) and 461-479 (domain III) significantly inhibited growth of xenografts originating from both pancreatic (BxPC3) and breast (JIMT-1) cancers. Combined therapy of HER-3 (461-471) epitope with HER-2 (266-296), HER-2 (597-626), HER-1 (418-435) and insulin-like growth factor receptor type I (IGF-1R) (56-81) vaccine antibodies and peptide mimics show enhanced antitumor effects in breast and pancreatic cancer cells. This study establishes the hypothesis that combination immunotherapy targeting different signal transduction pathways can provide effective antitumor immunity and long-term control of HER-1 and HER-2 overexpressing cancers.

Aggrecan-Like Biomimetic Proteoglycans (BPGs) Composed of Natural Chondroitin Sulfate Bristles Grafted onto Poly(acrylic acid) Core for Molecular Engineering of the Extracellular Matrix.

PubMed

Prudnikova, K; Lightfoot Vidal, S E; Sarkar, S; Yu, T; Yucha, R W; Ganesh, N; Penn, L S; Han, L; Schauer, C L; Vresilovic, E J; Marcolongo, M S

2018-05-10

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies. Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches. Copyright © 2018. Published by Elsevier Ltd.

Tri- and tetra-substituted cyclen based lanthanide(III) ion complexes as ribonuclease mimics: a study into the effect of log Ka, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP).

PubMed

Fanning, Ann-Marie; Plush, Sally E; Gunnlaugsson, Thorfinnur

2015-05-28

A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ1/2 = 5.87 × 10(3) h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37 °C; with τ1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37 °C. To further provide information on the role that the log Ka of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined. Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log Ka values for both MLOH and ML(OH)2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

One-pot synthesis of active copper-containing carbon dots with laccase-like activities

NASA Astrophysics Data System (ADS)

Ren, Xiangling; Liu, Jing; Ren, Jun; Tang, Fangqiong; Meng, Xianwei

2015-11-01

Herein, an effective strategy for designing a new type of nanozyme, blue fluorescent laccase mimics, is reported. Active copper-containing carbon dots (Cu-CDs) were synthesized through a simple, nontoxic and one-pot hydrothermal method, which showed favorable photoluminescence properties and good photostability under high-salt conditions or in a broad pH range (3.0-13.5). The Cu-CDs possessed intrinsic laccase-like activities and could catalyze the oxidation of the laccase substrate p-phenylenediamine (PPD) to produce a typical color change from colorless to brown. Poly(methacrylic acid sodium salt) (PMAA) not only was used as the carbon source and reducing agent, but also provided carboxyl groups to assist flocculation between Cu-CDs and polyacrylamide, which facilitated the removal of PPD. Importantly, the intrinsic fluorescence of the as-prepared Cu-CDs could indicate the presence of hydroquinone, one of the substrates of laccases, based on laccase mimics and fluorescence quenching.Herein, an effective strategy for designing a new type of nanozyme, blue fluorescent laccase mimics, is reported. Active copper-containing carbon dots (Cu-CDs) were synthesized through a simple, nontoxic and one-pot hydrothermal method, which showed favorable photoluminescence properties and good photostability under high-salt conditions or in a broad pH range (3.0-13.5). The Cu-CDs possessed intrinsic laccase-like activities and could catalyze the oxidation of the laccase substrate p-phenylenediamine (PPD) to produce a typical color change from colorless to brown. Poly(methacrylic acid sodium salt) (PMAA) not only was used as the carbon source and reducing agent, but also provided carboxyl groups to assist flocculation between Cu-CDs and polyacrylamide, which facilitated the removal of PPD. Importantly, the intrinsic fluorescence of the as-prepared Cu-CDs could indicate the presence of hydroquinone, one of the substrates of laccases, based on laccase mimics and fluorescence quenching. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04685h

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6.

PubMed

Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

2016-07-15

To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

PubMed Central

Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

2016-01-01

AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection. PMID:27559432

Decrease of reactive oxygen species-related biomarkers in the tissue-mimic 3D spheroid culture of human lung cells exposed to zinc oxide nanoparticles.

PubMed

Kim, Eunjoo; Jeon, Won Bae; Kim, Soonhyun; Lee, Soo-Keun

2014-05-01

Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and cell-matrix signaling and substantially different diffusion/transport pathways. To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared with elastin-like peptides modified with an arginine-glycine-aspartate motif. The 3D cells showed different cellular phenotypes, gene expression profiles, and functionalities compared to the 2D cultured cells. In gene array analysis, 3D cells displayed the induced extracellular matrix (ECM)-related biological functions such as cell-to-cell signaling and interaction, cellular function and maintenance, connective tissue development and function, molecular transport, and tissue morphology. Additionally, the expression of ECM-related molecules, such as laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3), was simultaneously induced at both mRNA and protein levels. When 0.08-50 microg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D cells, the cell proliferation was not significantly changed. The level of molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl-2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced in 2D culture when exposed to 10 microg/ml ZnO-NPs, but no significant decrease was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In conclusion, the tissue-mimic phenotype and functionality of 3D cells could be achieved through the elevated expression of ECM components. The 3D cells were expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic morphology would also be useful to simulate the diffusion/transport of the nanoparticles in vitro.

Antifungal activity of a β-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

PubMed

Raman, Namrata; Lee, Myung-Ryul; Rodríguez López, Angélica de L; Palecek, Sean P; Lynn, David M

2016-10-01

Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal β-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many α-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that β-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with β-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI. Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic β-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mimic Phosphorylation of a βC1 Protein Encoded by TYLCCNB Impairs Its Functions as a Viral Suppressor of RNA Silencing and a Symptom Determinant.

PubMed

Zhong, Xueting; Wang, Zhan Qi; Xiao, Ruyuan; Cao, Linge; Wang, Yaqin; Xie, Yan; Zhou, Xueping

2017-08-15

Phosphorylation of the βC1 protein encoded by the betasatellite of tomato yellow leaf curl China virus (TYLCCNB-βC1) by SNF1-related protein kinase 1 (SnRK1) plays a critical role in defense of host plants against geminivirus infection in Nicotiana benthamiana However, how phosphorylation of TYLCCNB-βC1 impacts its pathogenic functions during viral infection remains elusive. In this study, we identified two additional tyrosine residues in TYLCCNB-βC1 that are phosphorylated by SnRK1. The effects of TYLCCNB-βC1 phosphorylation on its functions as a viral suppressor of RNA silencing (VSR) and a symptom determinant were investigated via phosphorylation mimic mutants in N. benthamiana plants. Mutations that mimic phosphorylation of TYLCCNB-βC1 at tyrosine 5 and tyrosine 110 attenuated disease symptoms during viral infection. The phosphorylation mimics weakened the ability of TYLCCNB-βC1 to reverse transcriptional gene silencing and to suppress posttranscriptional gene silencing and abolished its interaction with N. benthamiana ASYMMETRIC LEAVES 1 in N. benthamiana leaves. The mimic phosphorylation of TYLCCNB-βC1 had no impact on its protein stability, subcellular localization, or self-association. Our data establish an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as a VSR and a symptom determinant and provide a mechanistic explanation of how SnRK1 functions as a host defense factor. IMPORTANCE Tomato yellow leaf curl China virus (TYLCCNV), which causes a severe yellow leaf curl disease in China, is a monopartite geminivirus associated with the betasatellite (TYLCCNB). TYLCCNB encodes a single pathogenicity protein, βC1 (TYLCCNB-βC1), which functions as both a viral suppressor of RNA silencing (VSR) and a symptom determinant. Here, we show that mimicking phosphorylation of TYLCCNB-βC1 weakens its ability to reverse transcriptional gene silencing, to suppress posttranscriptional gene silencing, and to interact with N. benthamiana ASYMMETRIC LEAVES 1. To our knowledge, this is the first report establishing an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as both a VSR and a symptom determinant and to provide a mechanistic explanation of how SNF1-related protein kinase 1 acts as a host defense factor. These findings expand the scope of phosphorylation-mediated defense mechanisms and contribute to further understanding of plant defense mechanisms against geminiviruses. Copyright © 2017 American Society for Microbiology.

Mimic Phosphorylation of a βC1 Protein Encoded by TYLCCNB Impairs Its Functions as a Viral Suppressor of RNA Silencing and a Symptom Determinant

PubMed Central

Zhong, Xueting; Wang, Zhan Qi; Xiao, Ruyuan; Cao, Linge; Wang, Yaqin

2017-01-01

ABSTRACT Phosphorylation of the βC1 protein encoded by the betasatellite of tomato yellow leaf curl China virus (TYLCCNB-βC1) by SNF1-related protein kinase 1 (SnRK1) plays a critical role in defense of host plants against geminivirus infection in Nicotiana benthamiana. However, how phosphorylation of TYLCCNB-βC1 impacts its pathogenic functions during viral infection remains elusive. In this study, we identified two additional tyrosine residues in TYLCCNB-βC1 that are phosphorylated by SnRK1. The effects of TYLCCNB-βC1 phosphorylation on its functions as a viral suppressor of RNA silencing (VSR) and a symptom determinant were investigated via phosphorylation mimic mutants in N. benthamiana plants. Mutations that mimic phosphorylation of TYLCCNB-βC1 at tyrosine 5 and tyrosine 110 attenuated disease symptoms during viral infection. The phosphorylation mimics weakened the ability of TYLCCNB-βC1 to reverse transcriptional gene silencing and to suppress posttranscriptional gene silencing and abolished its interaction with N. benthamiana ASYMMETRIC LEAVES 1 in N. benthamiana leaves. The mimic phosphorylation of TYLCCNB-βC1 had no impact on its protein stability, subcellular localization, or self-association. Our data establish an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as a VSR and a symptom determinant and provide a mechanistic explanation of how SnRK1 functions as a host defense factor. IMPORTANCE Tomato yellow leaf curl China virus (TYLCCNV), which causes a severe yellow leaf curl disease in China, is a monopartite geminivirus associated with the betasatellite (TYLCCNB). TYLCCNB encodes a single pathogenicity protein, βC1 (TYLCCNB-βC1), which functions as both a viral suppressor of RNA silencing (VSR) and a symptom determinant. Here, we show that mimicking phosphorylation of TYLCCNB-βC1 weakens its ability to reverse transcriptional gene silencing, to suppress posttranscriptional gene silencing, and to interact with N. benthamiana ASYMMETRIC LEAVES 1. To our knowledge, this is the first report establishing an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as both a VSR and a symptom determinant and to provide a mechanistic explanation of how SNF1-related protein kinase 1 acts as a host defense factor. These findings expand the scope of phosphorylation-mediated defense mechanisms and contribute to further understanding of plant defense mechanisms against geminiviruses. PMID:28539450

X-Ray Phantom Development For Observer Performance Studies

NASA Astrophysics Data System (ADS)

Kelsey, C. A.; Moseley, R. D.; Mettler, F. A.; Parker, T. W.

1981-07-01

The requirements for radiographic imaging phantoms for observer performance testing include realistic tasks which mimic at least some portion of the diagnostic examination presented in a setting which approximates clinically derived images. This study describes efforts to simulate chest and vascular diseases for evaluation of conventional and digital radiographic systems. Images of lung nodules, pulmonary infiltrates, as well as hilar and mediastinal masses are generated with a conventional chest phantom to make up chest disease test series. Vascular images are simulated by hollow tubes embedded in tissue density plastic with widening and narrowing added to mimic aneurysms and stenoses. Both sets of phantoms produce images which allow simultaneous determination of true positive and false positive rates as well as complete ROC curves.

Insertion of GaAs MMICs into EW systems

NASA Astrophysics Data System (ADS)

Schineller, E. R.; Pospishil, A.; Grzyb, J.

1989-09-01

Development activities on a microwave/mm-wave monolithic IC (MIMIC) program are described, as well as the methodology for inserting these GaAs IC chips into several EW systems. The generic EW chip set developed on the MIMIC program consists of 23 broadband chip types, including amplifiers, oscillators, mixers, switches, variable attenuators, power dividers, and power combiners. These chips are being designed for fabrication using the multifunction self-aligned gate process. The benefits from GaAs IC insertion are quantified by a comparison of hardware units fabricated with existing MIC and digital ECL technology and the same units manufactured with monolithic technology. It is found that major improvements in cost, reliability, size, weight, and performance can be realized. Examples illustrating the methodology for technology insertion are presented.

Malakoplakia mimics urinary bladder cancer: a case report.

PubMed

Ristić-Petrović, Ana; Stojnev, Slavica; Janković-Velicković, Ljubinka; Marjanović, Goran

2013-06-01

Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications.

Facially Amphipathic Glycopolymers Inhibit Ice Recrystallization.

PubMed

Graham, Ben; Fayter, Alice E R; Houston, Judith E; Evans, Rachel C; Gibson, Matthew I

2018-05-02

Antifreeze glycoproteins (AFGPs) from polar fish are the most potent ice recrystallization (growth) inhibitors known, and synthetic mimics are required for low-temperature applications such as cell cryopreservation. Here we introduce facially amphipathic glycopolymers that mimic the three-dimensional structure of AFGPs. Glycopolymers featuring segregated hydrophilic and hydrophobic faces were prepared by ring-opening metathesis polymerization, and their rigid conformation was confirmed by small-angle neutron scattering. Ice recrystallization inhibition (IRI) activity was reduced when a hydrophilic oxo-ether was installed on the glycan-opposing face, but significant activity was restored by incorporating a hydrophobic dimethylfulvene residue. This biomimetic strategy demonstrates that segregated domains of distinct hydrophilicity/hydrophobicity are a crucial motif to introduce IRI activity, which increases our understanding of the complex ice crystal inhibition processes.

78 FR 43216 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... tissue for grafting. Potential Commercial Applications: Tissue engineering. Simulation of physiological... oxygen diffusivity silicone hydrogel support structures that mimic tissue vasculature (e.g., capillary...

Conditions that Mimic Parkinson's

MedlinePlus

... risk of complications and have better quality of life. Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research Our research has ...

Novel Screening Tool for Stroke Using Artificial Neural Network.

PubMed

Abedi, Vida; Goyal, Nitin; Tsivgoulis, Georgios; Hosseinichimeh, Niyousha; Hontecillas, Raquel; Bassaganya-Riera, Josep; Elijovich, Lucas; Metter, Jeffrey E; Alexandrov, Anne W; Liebeskind, David S; Alexandrov, Andrei V; Zand, Ramin

2017-06-01

The timely diagnosis of stroke at the initial examination is extremely important given the disease morbidity and narrow time window for intervention. The goal of this study was to develop a supervised learning method to recognize acute cerebral ischemia (ACI) and differentiate that from stroke mimics in an emergency setting. Consecutive patients presenting to the emergency department with stroke-like symptoms, within 4.5 hours of symptoms onset, in 2 tertiary care stroke centers were randomized for inclusion in the model. We developed an artificial neural network (ANN) model. The learning algorithm was based on backpropagation. To validate the model, we used a 10-fold cross-validation method. A total of 260 patients (equal number of stroke mimics and ACIs) were enrolled for the development and validation of our ANN model. Our analysis indicated that the average sensitivity and specificity of ANN for the diagnosis of ACI based on the 10-fold cross-validation analysis was 80.0% (95% confidence interval, 71.8-86.3) and 86.2% (95% confidence interval, 78.7-91.4), respectively. The median precision of ANN for the diagnosis of ACI was 92% (95% confidence interval, 88.7-95.3). Our results show that ANN can be an effective tool for the recognition of ACI and differentiation of ACI from stroke mimics at the initial examination. © 2017 American Heart Association, Inc.

Self-enhanced N-(aminobutyl)-N-(ethylisoluminol) derivative-based electrochemiluminescence immunosensor for sensitive laminin detection using PdIr cubes as a mimic peroxidase

NASA Astrophysics Data System (ADS)

Jiang, Xinya; Wang, Huijun; Wang, Haijun; Zhuo, Ying; Yuan, Ruo; Chai, Yaqin

2016-04-01

Herein, a self-enhanced N-(aminobutyl)-N-(ethylisoluminol) (ABEI) derivative-based electrochemiluminescence (ECL) immunosensor was constructed for the determination of laminin (LN) using PdIr cubes as a mimic peroxidase for signal amplification. Initially, PdIr cubes with efficient peroxidase mimicking properties, large specific surface areas, and good stability and uniformity were synthesized. Then, l-cysteine (l-Cys) and ABEI were immobilized on the PdIr cubes to form the self-enhanced ECL nanocomplex (PdIr-l-Cys-ABEI). In this nanocomplex, PdIr cubes, whose catalytic constant is higher than that of horseradish peroxidase (HRP), could effectively catalyze H2O2 decomposition and thus enhance the ECL intensity of ABEI. Moreover, PdIr cubes can be easily modified with functional groups, which make them adaptable to desired supported platforms. On the other hand, l-Cys as a coreactant of ABEI could effectively enhance the luminous efficiency due to the intramolecular ECL reaction which could reduce the energy loss between l-Cys and ABEI by giving a shorter electron transfer distance. The developed strategy combined an ABEI derivative as a self-enhanced ECL luminophore and PdIr cubes as a mimic peroxidase, resulting in a significantly enhanced ECL signal output. Also, the strategy showed high sensitivity and selectivity for LN, which suggested that our new approach could be potentially applied in monitoring different proteins.

Applying a Multiple Group Causal Indicator Modeling Framework to the Reading Comprehension Skills of Third, Seventh, and Tenth Grade Students

PubMed Central

Tighe, Elizabeth L.; Wagner, Richard K.; Schatschneider, Christopher

2015-01-01

This study demonstrates the utility of applying a causal indicator modeling framework to investigate important predictors of reading comprehension in third, seventh, and tenth grade students. The results indicated that a 4-factor multiple indicator multiple indicator cause (MIMIC) model of reading comprehension provided adequate fit at each grade level. This model included latent predictor constructs of decoding, verbal reasoning, nonverbal reasoning, and working memory and accounted for a large portion of the reading comprehension variance (73% to 87%) across grade levels. Verbal reasoning contributed the most unique variance to reading comprehension at all grade levels. In addition, we fit a multiple group 4-factor MIMIC model to investigate the relative stability (or variability) of the predictor contributions to reading comprehension across development (i.e., grade levels). The results revealed that the contributions of verbal reasoning, nonverbal reasoning, and working memory to reading comprehension were stable across the three grade levels. Decoding was the only predictor that could not be constrained to be equal across grade levels. The contribution of decoding skills to reading comprehension was higher in third grade and then remained relatively stable between seventh and tenth grade. These findings illustrate the feasibility of using MIMIC models to explain individual differences in reading comprehension across the development of reading skills. PMID:25821346

Spontaneous Facial Mimicry Is Enhanced by the Goal of Inferring Emotional States: Evidence for Moderation of "Automatic" Mimicry by Higher Cognitive Processes.

PubMed

Murata, Aiko; Saito, Hisamichi; Schug, Joanna; Ogawa, Kenji; Kameda, Tatsuya

2016-01-01

A number of studies have shown that individuals often spontaneously mimic the facial expressions of others, a tendency known as facial mimicry. This tendency has generally been considered a reflex-like "automatic" response, but several recent studies have shown that the degree of mimicry may be moderated by contextual information. However, the cognitive and motivational factors underlying the contextual moderation of facial mimicry require further empirical investigation. In this study, we present evidence that the degree to which participants spontaneously mimic a target's facial expressions depends on whether participants are motivated to infer the target's emotional state. In the first study we show that facial mimicry, assessed by facial electromyography, occurs more frequently when participants are specifically instructed to infer a target's emotional state than when given no instruction. In the second study, we replicate this effect using the Facial Action Coding System to show that participants are more likely to mimic facial expressions of emotion when they are asked to infer the target's emotional state, rather than make inferences about a physical trait unrelated to emotion. These results provide convergent evidence that the explicit goal of understanding a target's emotional state affects the degree of facial mimicry shown by the perceiver, suggesting moderation of reflex-like motor activities by higher cognitive processes.

Soft 3D-Printed Phantom of the Human Kidney with Collecting System.

PubMed

Adams, Fabian; Qiu, Tian; Mark, Andrew; Fritz, Benjamin; Kramer, Lena; Schlager, Daniel; Wetterauer, Ulrich; Miernik, Arkadiusz; Fischer, Peer

2017-04-01

Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney's detailed anatomy and correctly corresponds to the targeted human cadaver's upper urinary tract. Soft materials with a tensile modulus of 0.8-1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion.

PubMed

Ouyang, Qin; Zhao, Jiewen; Chen, Quansheng

2014-09-02

Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers. Copyright © 2014 Elsevier B.V. All rights reserved.

Unraveling the Enzymatic Activity of Oxygenated Carbon Nanotubes and Their Application in the Treatment of Bacterial Infections.

PubMed

Wang, Huan; Li, Penghui; Yu, Dongqin; Zhang, Yan; Wang, Zhenzhen; Liu, Chaoqun; Qiu, Hao; Liu, Zhen; Ren, Jinsong; Qu, Xiaogang

2018-05-17

Carbon nanotubes (CNTs) and their derivatives have emerged as a series of efficient biocatalysts to mimic the function of natural enzymes in recent years. However, the unsatisfiable enzymatic efficiency usually limits their practical usage ranging from materials science to biotechnology. Here, for the first time, we present the synthesis of several oxygenated-group-enriched carbon nanotubes (o-CNTs) via a facile but green approach, as well as their usage as high-performance peroxidase mimics for biocatalytic reaction. Exhaustive characterizations of the enzymatic activity of o-CNTs have been provided by exploring the accurate effect of various oxygenated groups on their surface including carbonyl, carboxyl, and hydroxyl groups. Because of the "competitive inhibition" effect among all of these oxygenated groups, the catalytic efficiency of o-CNTs is significantly enhanced by weakening the presence of noncatalytic sites. Furthermore, the admirable enzymatic activity of these o-CNTs has been successfully applied in the treatment of bacterial infections, and the results of both in vitro and in vivo nanozyme-mediated bacterial clearance clearly demonstrate the feasibility of o-CNTs as robust peroxidase mimics to effectively decrease the bacterial viability under physiological conditions. We believe that the present study will not only facilitate the construction of novel efficient nanozymes by rationally adjusting the degree of the "competitive inhibition" effect, but also broaden the biological usage of o-CNT-based nanomaterials via their satisfactory enzymatic activity.

Impedimetric aptasensor for nuclear factor kappa B with peroxidase-like mimic coupled DNA nanoladders as enhancer.

PubMed

Peng, Kanfu; Zhao, Hongwen; Xie, Pan; Hu, Shuang; Yuan, Yali; Yuan, Ruo; Wu, Xiongfei

2016-07-15

In this work, we developed a sensitive and universal aptasensor for nuclear factor kappa B (NF-κB) detection based on peroxidase-like mimic coupled DNA nanoladders for signal amplification. The dsDNA formed by capture DNA S1 and NF-κB binding aptamer (NBA) was firstly assembled on electrode surface. The presence of target NF-κB then led to the leave of NBA from electrode surface and thus provided the binding sites for immobilizing initiator to trigger in situ formation of DNA nanoladders on electrode surface. Since the peroxidase-like mimic manganese (III) meso-tetrakis (4-Nmethylpyridyl)-porphyrin (MnTMPyP) interacts with DNA nanoladders via groove binding, the insoluble benzo-4-chlorohexadienone (4-CD) precipitation derived from the oxidation of 4-chloro-1-naphthol (4-CN) could be formed on electrode surface in the presence of H2O2, resulting in a significantly amplified EIS signal output for quantitative target analysis. As a result, the developed aptasensor showed a low detection limit of 7pM and a wide linear range of 0.01-20nM. Featured with high sensitivity and label-free capability, the proposed sensing scheme can thus offer new opportunities for achieving sensitive, selective and stable detection of different types of target proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

Spontaneous Facial Mimicry Is Enhanced by the Goal of Inferring Emotional States: Evidence for Moderation of “Automatic” Mimicry by Higher Cognitive Processes

PubMed Central

Murata, Aiko; Saito, Hisamichi; Schug, Joanna; Ogawa, Kenji; Kameda, Tatsuya

2016-01-01

A number of studies have shown that individuals often spontaneously mimic the facial expressions of others, a tendency known as facial mimicry. This tendency has generally been considered a reflex-like “automatic” response, but several recent studies have shown that the degree of mimicry may be moderated by contextual information. However, the cognitive and motivational factors underlying the contextual moderation of facial mimicry require further empirical investigation. In this study, we present evidence that the degree to which participants spontaneously mimic a target’s facial expressions depends on whether participants are motivated to infer the target’s emotional state. In the first study we show that facial mimicry, assessed by facial electromyography, occurs more frequently when participants are specifically instructed to infer a target’s emotional state than when given no instruction. In the second study, we replicate this effect using the Facial Action Coding System to show that participants are more likely to mimic facial expressions of emotion when they are asked to infer the target’s emotional state, rather than make inferences about a physical trait unrelated to emotion. These results provide convergent evidence that the explicit goal of understanding a target’s emotional state affects the degree of facial mimicry shown by the perceiver, suggesting moderation of reflex-like motor activities by higher cognitive processes. PMID:27055206

Selective extraction and determination of chlorogenic acids as combined quality markers in herbal medicines using molecularly imprinted polymers based on a mimic template.

PubMed

Ji, Wenhua; Zhang, Mingming; Yan, Huijiao; Zhao, Hengqiang; Mu, Yan; Guo, Lanping; Wang, Xiao

2017-12-01

We describe a solid-phase extraction adsorbent based on molecularly imprinted polymers (MIPs), prepared with use of a mimic template. The MIPs were used for the selective extraction and determination of three chlorogenic acids as combined quality markers for Lonicera japonica and Lianhua qingwen granules. The morphologies and surface groups of the MIPs were assessed by scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, and Fourier transform infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the MIPs were systematically compared with those of non-molecularly imprinted polymers. The MIPs showed high selectivity toward three structurally similar chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid). A procedure using molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography was established for the determination of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules. The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits of detection and limits of quantification for the three chlorogenic acids were 0.003 mg g -1 and 0.01 mg g -1 , respectively. The newly developed method is thus a promising technique for the enrichment and determination of chlorogenic acids from herbal medicines. Graphical Abstract Mimic molecularly imprinted polymers for the selective extraction of chlorogenic acids.

Tasting the difference: do multiple defence chemicals interact in Müllerian mimicry?

PubMed

Skelhorn, John; Rowe, Candy

2005-02-07

Müllerian mimicry, where two unpalatable species share a warning pattern, is classically believed to be a form of mutualism, where the species involved share the cost of predator education. The evolutionary dynamics of Müllerian mimicry have recently become a controversial subject, after mathematical models have shown that if minor alterations are made to assumptions about the way in which predators learn and forget about unpalatable prey, this textbook case of mutualism may not be mutualistic at all. An underlying assumption of these models is that Müllerian mimics possess the same defence chemical. However, some Müllerian mimics are known to possess different defence chemicals. Using domestic chicks as predators and coloured crumbs flavoured with either the same or different unpalatable chemicals as prey, we provide evidence that two defence chemicals can interact to enhance predator learning and memory. This indicates that Müllerian mimics that possess different defence chemicals are better protected than those that share a single defence chemical. These data provide insight into how multiple defence chemicals are perceived by birds,and how they influence the way birds learn and remember warningly coloured prey. They highlight the importance of considering how different toxins in mimicry rings can interact in the evolution and maintenance of Müllerian mimicry and could help to explain the remarkable variation in chemical defences found within and between species.

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats

PubMed Central

Chiang, Bing-Juin; Chen, Tien-Wen; Chung, Shiu-Dong; Lee, Way-Zen; Chien, Chiang-Ting

2017-01-01

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Transcystometrograms were performed in urethane-anesthetized rats. The in vitro and in vivo reactive oxygen species levels and pathological changes in formalin-fixed bladder sections were evaluated. Western blotting and immunohistochemistry elucidated the pathophysiological mechanisms of oxidative stress-induced apoptosis, autophagy, and pyroptosis. P-phenylenediamine increased voiding frequency, blood and urinary bladder levels of reactive oxygen species, and neutrophil and mast cell infiltration. It also upregulated biomarkers of autophagy (LC3 II), apoptosis (poly (ADP-ribose) polymerase), and pyroptosis (Caspase 1). WCT003 and WCT006 ameliorated reactive oxygen species production, inflammation, apoptosis, autophagy, pyroptosis, and bladder hyperactivity. P-phenylenediamine increased oxidative stress, inflammatory leukocytosis, autophagy, apoptosis, and pyroptosis formation within the urinary bladder. Novel synthetic nickel-containing superoxide dismutase mimics relieved p-phenylenediamine-induced bladder inflammation and voiding dysfunction. PMID:29285288

Selective mimics of strigolactone actions and their potential use for controlling damage caused by root parasitic weeds.

PubMed

Fukui, Kosuke; Ito, Shinsaku; Asami, Tadao

2013-01-01

Strigolactones (SLs) are a novel class of plant hormones and rhizosphere communication signals, although the molecular mechanisms underlying their activities have not yet been fully determined. Nor is their application in agriculture well developed. The importance of plant hormone agonists has been demonstrated in both basic and applied research, and chemicals that mimic strigolactone functions should greatly facilitate strigolactone research. Here, we report our discovery of a new phenoxyfuranone compound, 4-Br debranone (4BD), that shows similar activity to that of the major strigolactone (SL) analog GR24 in many aspects of a biological assay on plants. 4BD strongly inhibited tiller bud outgrowth in the SL-deficient rice mutant d10 at the same concentration as GR24, with no adverse effects, even during prolonged cultivation. This result was also observed in the Arabidopsis thaliana SL-deficient mutants max1, max3, and max4. However, the application of 4BD to the Arabidopsis SL-insensitive mutant max2 induced no morphological changes in it. The expression of SL biosynthetic genes was also reduced by 4BD treatment, probably via negative feedback regulation. However, in a seed germination assay on Striga hermonthica, a root parasitic plant, 4BD showed far less activity than GR24. These results suggest that 4BD is the first plant-specific strigolactone mimic.

Serotonin syndrome

MedlinePlus

... medicine). Drugs of abuse, such as ecstasy, LSD , cocaine , and amphetamines have also been associated with SS. ... can mimic those due to an overdose of cocaine, lithium, or an MAOI. If a person has ...

Bioluminescence.

ERIC Educational Resources Information Center

Jones, M. Gail

1993-01-01

Describes bioluminescence and the chemistry of how it occurs. Presents information for conducting the following classroom activities: (1) firefly mimic; (2) modeling deep-sea fish; (3) sea fireflies; and (4) the chemistry of light. (PR)

Presidential Green Chemistry Challenge: 2014 Greener Synthetic Pathways Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2014 award winner, Solazyme, engineered microalgae to produce oils tailored to customers’ needs that can mimic or enhance properties of traditional vegetable oils.

Development of an Arbitrary Waveform Membrane Stretcher for Dynamic Cell Culture

PubMed Central

Lau, Jason J.; Wang, Raymond M.; Black, Lauren D.

2014-01-01

In this paper, a novel cell stretcher design that mimics the real-time stretch of the heart wall is introduced. By culturing cells under stretched conditions that mimics the mechanical aspects of the native cardiac environment, better understanding on the role of biomechanical signaling on cell development can be achieved. The device utilizes a moving magnet linear actuator controlled through pulse-width modulated power combined with an automated closed loop feedback system for accurate generation of a designated mechanical stretch profile. The system’s capability to stretch a cell culture membrane and accuracy of the designated frequency and waveform production for cyclic stretching were evaluated. Temperature and degradation assessments as well as a scalable design demonstrated the system’s cell culture application for long term, in vitro studies. PMID:24473700

A strong and stretchable self-healing film with self-activated pressure sensitivity for potential artificial skin applications

PubMed Central

Hou, Chengyi; Huang, Tao; Wang, Hongzhi; Yu, Hao; Zhang, Qinghong; Li, Yaogang

2013-01-01

Artificial skin, which mimics the functions of natural skin, will be very important in the future for robots used by humans in daily life. However, combining skin's pressure sensitivity and mechanical self-healing properties in a man-made material remains a challenging task. Here, we show that graphene and polymers can be integrated into a thin film which mimics both the mechanical self-healing and pressure sensitivity behavior of natural skin without any external power supply. Its ultimate strain and tensile strength are even two and ten times larger than the corresponding values of human skin, respectively. It also demonstrates highly stable sensitivity to a very light touch (0.02 kPa), even in bending or stretching states. PMID:24190511

Lectins with anti-HIV activity: a review.

PubMed

Akkouh, Ouafae; Ng, Tzi Bun; Singh, Senjam Sunil; Yin, Cuiming; Dan, Xiuli; Chan, Yau Sang; Pan, Wenliang; Cheung, Randy Chi Fai

2015-01-06

Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.

An α‐Helix‐Mimicking 12,13‐Helix: Designed α/β/γ‐Foldamers as Selective Inhibitors of Protein–Protein Interactions

PubMed Central

Grison, Claire M.; Miles, Jennifer A.; Robin, Sylvie

2016-01-01

Abstract A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein–protein interactions (PPIs). In this work, trans‐2‐aminocyclobutanecarboxylic acid (tACBC) was used as the key β‐amino acid component in the design of α/β/γ‐peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild‐type α‐peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction. PMID:27467859

An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions.

PubMed

Grison, Claire M; Miles, Jennifer A; Robin, Sylvie; Wilson, Andrew J; Aitken, David J

2016-09-05

A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Multicomponent micropatterned sol-gel materials by capillary molding

NASA Astrophysics Data System (ADS)

Lochhead, Michael J.; Yager, Paul

1997-10-01

A physically and chemically benign method for patterning multiple sol-gel materials onto a single substrate is described. Structures are demonstrated for potential micro- optical chemical sensor, biosensor, and waveguiding applications. Fabrication is based on the micro molding in capillaries (MIMIC) approach. A novel mold design allows several sols to be cast simultaneously. Closely spaced, organically modified silica ridges containing fluorescent dyes are demonstrated. Ridges have cross sectional dimensions from one to 50 micrometers and are centimeters in length. Processing issues, particularly those related to mold filling, are discussed in detail. Because sol-gel MIMIC avoids the harsh physical and chemical environments normally associated with patterning, the approach allows full exploitation of sol- gel processing advantages, such as the ability to entrap sensitive organic dopant molecules in the sol-gel matrix.

The research of laryngeal joints to reconstruction and modeling.

PubMed

Zhang, Yi; Shi, Tingchun

2014-01-01

Larynx has a complex structure with joints and multiple functions. In order to study the artificial larynx and artificial auricle scaffold, a three-dimensional digital model of laryngeal joint is established in this paper using MIMICS with its biomechanical properties analyzed and calculated by using the finite element method. This model is based on the CT scanned images of 281 layers with an interlamellar spacing of 1.25 mm. The obtained data are denoised, segmented and smoothed before being loaded into MIMICS. By further optimizations, an accurate and complete 3D model can be obtained. Subsequently, a 3D FEM of the normal larynx joint is performed which allows observations from any dimensions and angles. Compared with natural laryngeal joint, this model has good geometric similarity and mechanically similar throat voicing functions.

The association of carotid cavernous fistula with Graves’ ophthalmopathy

PubMed Central

Celik, Ozlem; Buyuktas, Deram; Islak, Civan; Sarici, A Murat; Gundogdu, A Sadi

2013-01-01

Graves’ ophthalmopathy (GO) is one of the frequent manifestations of the disorder which is an inflammatory process due to fibroblast infiltration, fibroblast proliferation and accumulation of glycosaminoglycans. Eye irritation, dryness, excessive tearing, visual blurring, diplopia, pain, visual loss, retroorbital discomfort are the symptoms and they can mimic carotid cavernous fistulas. Carotid cavernous fistulas are abnormal communications between the carotid arterial system and the cavernous sinus. The clinical manifestations of GO can mimic the signs of carotid cavernous fistulas. Carotid cavernous fistulas should be considered in the differential diagnosis of the GO patients especially who are not responding to the standard treatment and when there is a unilateral or asymmetric eye involvement. Here we report the second case report with concurrent occurrence of GO and carotid cavernous fistula in the literature. PMID:23571267

Enhanced photocatalytic hydrogen production from an MCM-41-immobilized photosensitizer-[Fe-Fe] hydrogenase mimic dyad.

PubMed

Wang, Wen; Yu, Tianjun; Zeng, Yi; Chen, Jinping; Yang, Guoqiang; Li, Yi

2014-11-01

A covalently linked photosensitizer-catalytic center dyad Ps-Hy, consisting of two bis(2-phenylpyridine)(2,2'-bipyridine)iridium(iii) chromophores (Ps) and a diiron hydrogenase mimic (Hy) was constructed by using click reaction. Ps-Hy was incorporated into K(+)-exchanged molecular sieve MCM-41 to form a composite (Ps-Hy@MCM-41), which has been successfully applied to the photochemical production of hydrogen. The catalytic activity of Ps-Hy@MCM-41 is ∼3-fold higher as compared with that of Ps-Hy in the absence of MCM-41. The incorporation of Ps-Hy into MCM-41 stabilizes the catalyst, and consequently, advances the photocatalysis. The present study provides a potential strategy for improving catalytic efficiency of artificial photosynthesis systems using mesoporous molecular sieves.

Additively manufactured metallic porous biomaterials based on minimal surfaces: A unique combination of topological, mechanical, and mass transport properties.

PubMed

Bobbert, F S L; Lietaert, K; Eftekhari, A A; Pouran, B; Ahmadi, S M; Weinans, H; Zadpoor, A A

2017-04-15

Porous biomaterials that simultaneously mimic the topological, mechanical, and mass transport properties of bone are in great demand but are rarely found in the literature. In this study, we rationally designed and additively manufactured (AM) porous metallic biomaterials based on four different types of triply periodic minimal surfaces (TPMS) that mimic the properties of bone to an unprecedented level of multi-physics detail. Sixteen different types of porous biomaterials were rationally designed and fabricated using selective laser melting (SLM) from a titanium alloy (Ti-6Al-4V). The topology, quasi-static mechanical properties, fatigue resistance, and permeability of the developed biomaterials were then characterized. In terms of topology, the biomaterials resembled the morphological properties of trabecular bone including mean surface curvatures close to zero. The biomaterials showed a favorable but rare combination of relatively low elastic properties in the range of those observed for trabecular bone and high yield strengths exceeding those reported for cortical bone. This combination allows for simultaneously avoiding stress shielding, while providing ample mechanical support for bone tissue regeneration and osseointegration. Furthermore, as opposed to other AM porous biomaterials developed to date for which the fatigue endurance limit has been found to be ≈20% of their yield (or plateau) stress, some of the biomaterials developed in the current study show extremely high fatigue resistance with endurance limits up to 60% of their yield stress. It was also found that the permeability values measured for the developed biomaterials were in the range of values reported for trabecular bone. In summary, the developed porous metallic biomaterials based on TPMS mimic the topological, mechanical, and physical properties of trabecular bone to a great degree. These properties make them potential candidates to be applied as parts of orthopedic implants and/or as bone-substituting biomaterials. Bone-substituting biomaterials aim to mimic bone properties. Although mimicking some of bone properties is feasible, biomaterials that could simultaneously mimic all or most of the relevant bone properties are rare. We used rational design and additive manufacturing to develop porous metallic biomaterials that exhibit an interesting combination of topological, mechanical, and mass transport properties. The topology of the developed biomaterials resembles that of trabecular bone including a mean curvature close to zero. Moreover, the developed biomaterials show an unusual combination of low elastic modulus to avoid stress shielding and high strength to provide mechanical support. The fatigue resistance of the developed biomaterials is also exceptionally high, while their permeability is in the range of values reported for bone. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pseudotumor Cerebri

MedlinePlus

... bry) occurs when the pressure inside your skull (intracranial pressure) increases for no obvious reason. Symptoms mimic those ... obese. When no underlying cause for the increased intracranial pressure can be discovered, pseudotumor cerebri may also be ...

Structure of a High-Affinity

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

Saphire, E.O.; Montero, M.; Menendez, A.

2007-07-13

The human antibody b12 recognizes a discontinuous epitope on gp120 and is one of the rare monoclonal antibodies that neutralize a broad range of primary human immunodeficiency virus type 1 (HIV-1) isolates. We previously reported the isolation of B2.1, a dimeric peptide that binds with high specificity to b12 and competes with gp120 for b12 antibody binding. Here, we show that the affinity of B2.1 was improved 60-fold over its synthetic-peptide counterpart by fusing it to the N terminus of a soluble protein. This affinity, which is within an order of magnitude of that of gp120, probably more closely reflectsmore » the affinity of the phage-borne peptide. The crystal structure of a complex between Fab of b12 and B2.1 was determined at 1.8 Angstrom resolution. The structural data allowed the differentiation of residues that form critical contacts with b12 from those required for maintenance of the antigenic structure of the peptide, and revealed that three contiguous residues mediate B2.1's critical contacts with b12. This single region of critical contact between the B2.1 peptide and the b12 paratope is unlikely to mimic the discontinuous key binding residues involved in the full b12 epitope for gp120, as previously identified by alanine scanning substitutions on the gp120 surface. These structural observations are supported by experiments that demonstrate that B2.1 is an ineffective immunogenic mimic of the b12 epitope on gp120. Indeed, an extensive series of immunizations with B2.1 in various forms failed to produce gp120 cross-reactive sera. The functional and structural data presented here, however, suggest that the mechanism by which b12 recognizes the two antigens is very different. Here, we present the first crystal structure of peptide bound to an antibody that was originally raised against a discontinuous protein epitope. Our results highlight the challenge of producing immunogens that mimic discontinuous protein epitopes, and the necessity of combining complementary experimental approaches in analyzing the antigenic and immunogenic properties of putative molecular mimics.« less

Design and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation

PubMed Central

Wu, Xiao; Hayes, Don; Zwischenberger, Joseph B; Kuhn, Robert J; Mansour, Heidi M

2013-01-01

The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine. PMID:23403805

Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche.

PubMed

Aguado, Brian A; Caffe, Jordan R; Nanavati, Dhaval; Rao, Shreyas S; Bushnell, Grace G; Azarin, Samira M; Shea, Lonnie D

2016-03-01

Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM-coated poly(ε-caprolactone) (PCL) scaffolds as mimics of the pre-metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM-coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. The pre-metastatic niche consists partially of ECM proteins that promote metastatic cell colonization to a target organ. We present a biomaterials-based approach to mimic this niche and identify ECM mediators of colonization. Using murine breast cancer models, we implanted microporous PCL scaffolds to recruit colonizing tumor cells in vivo. As a strategy to modulate colonization, we coated scaffolds with various ECM proteins, including decellularized lung and liver matrix from tumor-bearing mice. After characterizing the organ matrices using proteomics, myeloperoxidase was identified as an ECM protein contributing to colonization and validated using our scaffold. Our scaffold provides a platform to identify novel contributors to colonization and allows for the capture of colonizing tumor cells for a variety of downstream clinical applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Artificial neural networks in models of specialization, guild evolution and sympatric speciation.

PubMed

Holmgren, Noél M A; Norrström, Niclas; Getz, Wayne M

2007-03-29

Sympatric speciation can arise as a result of disruptive selection with assortative mating as a pleiotropic by-product. Studies on host choice, employing artificial neural networks as models for the host recognition system in exploiters, illustrate how disruptive selection on host choice coupled with assortative mating can arise as a consequence of selection for specialization. Our studies demonstrate that a generalist exploiter population can evolve into a guild of specialists with an 'ideal free' frequency distribution across hosts. The ideal free distribution arises from variability in host suitability and density-dependent exploiter fitness on different host species. Specialists are less subject to inter-phenotypic competition than generalists and to harmful mutations that are common in generalists exploiting multiple hosts. When host signals used as cues by exploiters coevolve with exploiter recognition systems, our studies show that evolutionary changes may be continuous and cyclic. Selection changes back and forth between specialization and generalization in the exploiters, and weak and strong mimicry in the hosts, where non-defended hosts use the host investing in defence as a model. Thus, host signals and exploiter responses are engaged in a red-queen mimicry process that is ultimately cyclic rather then directional. In one phase, evolving signals of exploitable hosts mimic those of hosts less suitable for exploitation (i.e. the model). Signals in the model hosts also evolve through selection to escape the mimic and its exploiters. Response saturation constraints in the model hosts lead to the mimic hosts finally perfecting its mimicry, after which specialization in the exploiter guild is lost. This loss of exploiter specialization provides an opportunity for the model hosts to escape their mimics. Therefore, this cycle then repeats. We suggest that a species can readily evolve sympatrically when disruptive selection for specialization on hosts is the first step. In a sexual reproduction setting, partial reproductive isolation may first evolve by mate choice being confined to individuals on the same host. Secondly, this disruptive selection will favour assortative mate choice on genotype, thereby leading to increased reproductive isolation.

Quantifying the Interannual Variability in Global Carbon Fluxes from Heterotrophic Respiration using a Testbed and Pulse Response Modeling Approach.

NASA Astrophysics Data System (ADS)

Basile, S.; Wieder, W. R.; Hartman, M. D.; Keppel-Aleks, G.

2017-12-01

The atmospheric growth rate of carbon dioxide (CO2) varies interannually and is strongly correlated with climate factors, including temperature and drought. These climate drivers affect vegetation productivity and the rate of respiration of organic matter to CO2 (heterotrophic respiration). Here we quantified the interannual variability in global carbon fluxes from heterotrophic respiration and their relationship to climate drivers. We used a novel testbed approach to simulate respiration, then simulated the imprint that these modeled heterotrophic fluxes have on atmospheric CO2 using an idealized pulse response model. Two of the testbed formulations (MIMICS and CORPSE) are microbially explicit by incorporation of microbial physiological tradeoffs and microbial activity in soil near fine roots (rhizosphere soils), respectively, while the third model (CASA) uses a CENTURY-like microbially implicit framework. Modeled respiration exhibited subtle differences, with MIMICS showing the largest seasonal amplitude in the Northern Hemisphere and the strongest correlation with global temperature variations. At Mauna Loa (MLO) the simulated seasonal CO2 amplitude in response to global heterotrophic respiration ranged by a factor of 1.5 across the models with the MIMICS and CASA models producing the higher amplitude responses between 1987 and 2006. The seasonal CO2 amplitude at MLO varied by about 5% interannually, with the largest variation in the MIMICS model. In the Northern Hemisphere there was a similar response range in average peak-to-trough seasonal CO2 but all models showed slightly higher amplitude values. Comparatively in the Northern Hemisphere, the average seasonal CO2 amplitude in response to respiration ranged between 30%-41% of the seasonal CO2 amplitude in response to net primary productivity. We expect that exploring the imprint of heterotrophic respiration on atmospheric CO2 from these three different models will improve our understanding of the imprint that heterotrophic respiration imparts on atmospheric data. The aim of this work is to ultimately yield an approach for combining CO2 observations with remote sensing-based observations of terrestrial productivity to produce regional constraints on heterotrophic respiration.

Dry solution to a sticky problem

PubMed Central

KARP, JEFFREY M.; LANGER, ROBERT

2011-01-01

Sticking plasters revolutionized the protection of minor wounds, but they’re not ideal for fragile skin. A material that mimics the adhesive properties of certain beetles’ feet might provide a solution. PMID:21886155

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

DOE-funded research projects that are integrating cybersecurity controls with power systems principles Management, a hardware and software system that mimics the communications, power systems, and cybersecurity

The Design of Molecular Hosts, Guests, and Their Complexes.

ERIC Educational Resources Information Center

Cram, Donald J.

1988-01-01

Describes the origins, definitions, tools, and principles of host-guest chemistry. Gives examples of chiral recognition in complexation, of partial transacylase mimics, of caviplexes, and of a synthetic molecular cell. (Author/RT)

Infant Development: Milestones from 4 to 6 Months

MedlinePlus

... thought development. Your baby will soak in your words and might even mimic the sounds you make. Start with books featuring large, brightly colored pictures. Describe what's happening on each page. Point to ...

Abusive Head Trauma (Shaken Baby Syndrome)

MedlinePlus

... AHT are brought in for medical care as "silent injuries." In other words, parents or caregivers often ... for: S hushing (by using "white noise" or rhythmic sounds that mimic the constant whir of noise in ...

PHEOCHROMOCYTOMA: AN ENDOCRINE STRESS MIMICKING DISORDER

PubMed Central

Kantorovich, Vitaly; Eisenhofer, Graeme; Pacak, Karel

2008-01-01

Pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. PMID:19120142

Environmental and management injury in hardwood tree plantations

Treesearch

John Seifert; Keith Woeste

2005-01-01

The injuries described in this publication sometimes mimic those caused by animals, insects, and diseases. Some environmental and management-related ijuries can be treated, but it is best to prevent their recurrence.

EPA NRMRL green Infrastructure research

EPA Science Inventory

Green Infrastructure is an engineering approach to wet weather flow management that uses infiltration, evapotranspiration, capture and reuse to better mimic the natural drainage processes than traditional gray systems. Green technologies supplement gray infrastructure to red...

Delaying Your Period with Birth Control Pills

MedlinePlus

... the pill to have more control over your cycle. By Mayo Clinic Staff Are you interested in ... pills are designed to mimic a natural menstrual cycle. A traditional pill pack contains 28 pills, but ...

Mesenteric Lymphadenitis

MedlinePlus

... results from an intestinal infection. It mainly affects children and teens. This painful condition can mimic the warning signs ... see a doctor Abdominal pain is common in children and teens, and it can be hard to know when ...

3D Printed, Customized Cranial Implant for Surgical Planning

NASA Astrophysics Data System (ADS)

Bogu, Venkata Phanindra; Ravi Kumar, Yennam; Asit Kumar, Khanra

2018-06-01

The main objective of the present work is to model cranial implant and printed in FDM machine (printer model used: mojo). Actually this is peculiar case and the skull has been damaged in frontal, parietal and temporal regions and a small portion of frontal region damaged away from saggital plane, complexity is to fill this frontal region with proper curvature. The Patient CT-data (Number of slices was 381 and thickness of each slice is 0.488 mm) was processed in mimics14.1 software, mimics file was sent to 3-matic software and calculated thickness of skull at different sections where cranial implant is needed then corrected the edges of cranial implant to overcome CSF (cerebrospinal fluid) leakage and proper fitting. Finally the implant average thickness is decided as 2.5 mm and printed in FDM machine with ABS plastic.

Reduced graphene oxide aerogel networks with soft interfacial template for applications in bone tissue regeneration

NASA Astrophysics Data System (ADS)

Asha, S.; Ananth, A. Nimrodh; Jose, Sujin P.; Rajan, M. A. Jothi

2018-05-01

Reduced Graphene Oxide aerogels (A-RGO), functionalized with chitosan, were found to induce and/or accelerate the mineralization of hydroxyapatite. The functionalized chitosan acts as a soft interfacial template on the surface of A-RGO assisting the growth of hydroxyapatite particles. The mineralization on these soft aerogel networks was performed by soaking the aerogels in simulated body fluid, relative to time. Polymer-induced mineralization exhibited an ordered arrangement of hydroxyapatite particles on reduced graphene oxide aerogel networks with a higher crystalline index (IC) of 1.7, which mimics the natural bone formation indicating the importance of the polymeric interfacial template. These mineralized aerogels which mimic the structure and composition of natural bone exhibit relatively higher rate of cell proliferation, osteogenic differentiation and osteoid matrix formation proving it to be a potential scaffold for bone tissue regeneration.

Fractional Brownian motion run with a multi-scaling clock mimics diffusion of spherical colloids in microstructural fluids.

PubMed

Park, Moongyu; Cushman, John Howard; O'Malley, Dan

2014-09-30

The collective molecular reorientations within a nematic liquid crystal fluid bathing a spherical colloid cause the colloid to diffuse anomalously on a short time scale (i.e., as a non-Brownian particle). The deformations and fluctuations of long-range orientational order in the liquid crystal profoundly influence the transient diffusive regimes. Here we show that an anisotropic fractional Brownian process run with a nonlinear multiscaling clock effectively mimics this collective and transient phenomenon. This novel process has memory, Gaussian increments, and a multiscale mean square displacement that can be chosen independently from the fractal dimension of a particle trajectory. The process is capable of modeling multiscale sub-, super-, or classical diffusion. The finite-size Lyapunov exponents for this multiscaling process are defined for future analysis of related mixing processes.

Cooperative interplay of let-7 mimic and HuR with MYC RNA.

PubMed

Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew C J; Wilce, Jacqueline A

2015-01-01

Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites.

Benchmark results in the 2D lattice Thirring model with a chemical potential

NASA Astrophysics Data System (ADS)

Ayyar, Venkitesh; Chandrasekharan, Shailesh; Rantaharju, Jarno

2018-03-01

We study the two-dimensional lattice Thirring model in the presence of a fermion chemical potential. Our model is asymptotically free and contains massive fermions that mimic a baryon and light bosons that mimic pions. Hence, it is a useful toy model for QCD, especially since it, too, suffers from a sign problem in the auxiliary field formulation in the presence of a fermion chemical potential. In this work, we formulate the model in both the world line and fermion-bag representations and show that the sign problem can be completely eliminated with open boundary conditions when the fermions are massless. Hence, we are able accurately compute a variety of interesting quantities in the model, and these results could provide benchmarks for other methods that are being developed to solve the sign problem in QCD.

3D Printed, Customized Cranial Implant for Surgical Planning

NASA Astrophysics Data System (ADS)

Bogu, Venkata Phanindra; Ravi Kumar, Yennam; Asit Kumar, Khanra

2016-06-01

The main objective of the present work is to model cranial implant and printed in FDM machine (printer model used: mojo). Actually this is peculiar case and the skull has been damaged in frontal, parietal and temporal regions and a small portion of frontal region damaged away from saggital plane, complexity is to fill this frontal region with proper curvature. The Patient CT-data (Number of slices was 381 and thickness of each slice is 0.488 mm) was processed in mimics14.1 software, mimics file was sent to 3-matic software and calculated thickness of skull at different sections where cranial implant is needed then corrected the edges of cranial implant to overcome CSF (cerebrospinal fluid) leakage and proper fitting. Finally the implant average thickness is decided as 2.5 mm and printed in FDM machine with ABS plastic.

A Photoisomerizing Rhodopsin Mimic Observed at Atomic Resolution.

PubMed

Nosrati, Meisam; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James H

2016-07-20

The members of the rhodopsin family of proteins are involved in many essential light-dependent processes in biology. Specific photoisomerization of the protein-bound retinylidene PSB at a specified wavelength range of light is at the heart of all of these systems. Nonetheless, it has been difficult to reproduce in an engineered system. We have developed rhodopsin mimics, using intracellular lipid binding protein family members as scaffolds, to study fundamental aspects of protein/chromophore interactions. Herein we describe a system that specifically isomerizes the retinylidene protonated Schiff base both thermally and photochemically. This isomerization has been characterized at atomic resolution by quantitatively interconverting the isomers in the crystal both thermally and photochemically. This event is accompanied by a large pKa change of the imine similar to the pKa changes observed in bacteriorhodopsin and visual opsins during isomerization.

Electrospun nanofibres to mimic natural hierarchical structure of tissues: application in musculoskeletal regeneration.

PubMed

Sankar, Sharanya; Sharma, Chandra S; Rath, Subha N; Ramakrishna, Seeram

2018-01-01

Biomimetic scaffolds mimicking the natural hierarchical structure of tissues have recently attracted the interest of researchers and provide a promising strategy to resemble the nonhomogeneous property of tissues. This review provides an overview of the various hierarchical length scales in the native tissues of the musculoskeletal system. It further focuses on electrospinning as a technique to mimic the tissue structures with specific emphasis on bone. The effect of cellular alignment, infiltration, vascularisation, and differentiation in these nanostructures has also been discussed. An outline of the various additive manufacturing techniques in combination with electrospinning has been elaborated. The review concludes with the challenges and future directions to understand the intricacies of bottom-up approach to engineer the systems at a macroscale. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A pseudoatom in a cage: trimetallofullerene Y(3)@C(80) mimics y(3)n@c(80) with nitrogen substituted by a pseudoatom.

PubMed

Popov, Alexey A; Zhang, Lin; Dunsch, Lothar

2010-02-23

Y(3)C(80) obtained in the synthesis of nitride clusterfullerenes Y(3)N@C(2n) (2n = 80-88) by the reactive atmosphere method is found to be a genuine trimetallofullerene, Y(3)@C(80), with low ionization potential and divalent state of yttrium atoms. DFT studies of the electronic structure of Y(3)@C(80) show that this molecule mimics Y(3)N@C(80) with the pseudoatom (PA) instead of the nitrogen atom. Topology analysis of the electron density and electron localization function show that yttrium atoms form Y-PA bonds rather than direct Y-Y bonds. Molecular dynamics simulations show that the Y(3)PA cluster is as rigid as Y(3)N and rotates inside the fullerene cage as a single entity.

New daily persistent headache.

PubMed

Evans, Randolph W

2003-08-01

New daily persistent headache (NDPH), which is the acute onset of headache within 3 days and is persistent for 15 days or more each month for at least 3 months, is a predominantly female heterogeneous subtype of chronic daily headache, typically with migraine features of unknown etiology. NDPH may be a presentation of other primary headaches such as new onset migraine, tension, or benign thunderclap headache. The headaches can be difficult to treat. The diagnosis is one of excluding the many secondary types or NDPH mimics, which is especially critical early in the course of the disease when a secondary etiology is more likely. NDPH mimics include postmeningitis headache, NDPH with medication rebound, neoplasms, temporal arteritis, chronic meningitis, chronic subdural hematoma, post-traumatic headaches, sphenoid sinusitis, hypertension, subarachnoid hemorrhage, low cerebrospinal fluid pressure syndrome, cervical artery dissections, pseudotumor cerebri without papilledema, and cerebral venous thrombosis.

Nanocomposites for bone tissue regeneration.

PubMed

Sahoo, Nanda Gopal; Pan, Yong Zheng; Li, Lin; He, Chao Bin

2013-04-01

Natural bone tissue possesses a nanocomposite structure that provides appropriate physical and biological properties. For bone tissue regeneration, it is crucial for the biomaterial to mimic living bone tissue. Since no single type of material is able to mimic the composition, structure and properties of native bone, nanocomposites are the best choice for bone tissue regeneration as they can provide the appropriate matrix environment, integrate desirable biological properties, and provide controlled, sequential delivery of multiple growth factors for the different stages of bone tissue regeneration. This article reviews the composition, structure and properties of advanced nanocomposites for bone tissue regeneration. It covers aspects of interest such as the biomimetic synthesis of bone-like nanocomposites, guided bone regeneration from inert biomaterials and bioactive nanocomposites, and nanocomposite scaffolds for bone tissue regeneration. The design, fabrication, and in vitro and in vivo characterization of such nanocomposites are reviewed.

Hybrid Elastin-like Polypeptide–Polyethylene Glycol (ELP-PEG) Hydrogels with Improved Transparency and Independent Control of Matrix Mechanics and Cell Ligand Density

PubMed Central

2015-01-01

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP’s lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell–matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics. PMID:25111283

Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density.

PubMed

Wang, Huiyuan; Cai, Lei; Paul, Alexandra; Enejder, Annika; Heilshorn, Sarah C

2014-09-08

Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin-like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP's lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP-polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 °C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell-matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics.

MLH1 as a direct target of MiR-155 and a potential predictor of favorable prognosis in pancreatic cancer.

PubMed

Liu, Wen-Jing; Zhao, Yu-Pei; Zhang, Tai-Ping; Zhou, Li; Cui, Quan-Cai; Zhou, Wei-Xun; You, Lei; Chen, Ge; Shu, Hong

2013-08-01

The regulation of Mut L homologue 1 (MLH1) expression by microRNA (miR)-155 and its prognostic significance in pancreatic cancer (PC) remain to be elucidated. This study aimed to address the issues. MiR-155 mimics and inhibitor were transfected to PC cell lines, Panc-1 and Capan-1. Expression of MLH1 was subsequently evaluated. Then, luciferase activity was detected after miR-155 mimics and pRL-TK plasmids containing wild-type and mutant 3'UTRs of MLH1 mRNA were co-transfected. Finally, immunohistochemical staining for MLH1 was performed in PC samples. Transfection of miR-155 mimics and inhibitor led to reversely altered protein expressions of miR-155 and MLH1, whereas the corresponding mRNA expressions were similar. A significant decrease in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid was shown in contrast to those transfected with the mutant one. In addition, MLH1 was less expressed in tumor than in para-tumor tissues of PC. Extensive MLH1 expression was significantly associated with favorable differentiation and less lymph node metastasis. MLH1 expression was found to be a prognosticator in univariate analysis, and being of marginally significant impact in multivariate test. MLH1 might serve as a direct target of miR-155 and a potential prognosis predictor in PC.

Engineered three-dimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment.

PubMed

Hockemeyer, K; Janetopoulos, C; Terekhov, A; Hofmeister, W; Vilgelm, A; Costa, Lino; Wikswo, J P; Richmond, A

2014-07-01

Stromal cells in the tumor microenvironment play a key role in the metastatic properties of a tumor. It is recognized that cancer-associated fibroblasts (CAFs) and endothelial cells secrete factors capable of influencing tumor cell migration into the blood or lymphatic vessels. We developed a microfluidic device that can be used to image the interactions between stromal cells and tumor cell spheroids in a three dimensional (3D) microenvironment while enabling external control of interstitial flow at an interface, which supports endothelial cells. The apparatus couples a 200-μm channel with a semicircular well to mimic the interface of a blood vessel with the stroma, and the design allows for visualization of the interactions of interstitial flow, endothelial cells, leukocytes, and fibroblasts with the tumor cells. We observed that normal tissue-associated fibroblasts (NAFs) contribute to the "single file" pattern of migration of tumor cells from the spheroid in the 3D microenvironment. In contrast, CAFs induce a rapid dispersion of tumor cells out of the spheroid with migration into the 3D matrix. Moreover, treatment of tumor spheroid cultures with the chemokine CXCL12 mimics the effect of the CAFs, resulting in similar patterns of dispersal of the tumor cells from the spheroid. Conversely, addition of CXCL12 to co-cultures of NAFs with tumor spheroids did not mimic the effects observed with CAF co-cultures, suggesting that NAFs produce factors that stabilize the tumor spheroids to reduce their migration in response to CXCL12.

Ubiquitous Release Of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells

PubMed Central

Kanlikilicer, Pinar; Rashed, Mohammed H.; Bayraktar, Recep; Mitra, Rahul; Ivan, Cristina; Aslan, Burcu; Zhang, Xinna; Filant, Justyna; Silva, Andreia M.; Rodriguez-Aguayo, Cristian; Bayraktar, Emine; Pichler, Martin; Ozpolat, Bulent; Calin, George A.; Sood, Anil K.; Lopez-Berestein, Gabriel

2017-01-01

Cancer cells actively promote their tumorigenic behavior by reprogramming gene expression. Loading intraluminal vesicles with specific miRNAs and releasing them into the tumor microenvironment as exosomes is one mechanism of reprogramming whose regulation remains to be elucidated. Here, we report that miR-6126 is ubiquitously released in high abundance from both chemosensitive and chemoresistant ovarian cancer cells via exosomes. Overexpression of miR-6126 was confirmed in healthy ovarian tissue compared to ovarian cancer patient samples and correlated with better overall survival in high-grade serous ovarian cancer patients. miR-6126 acted as a tumor suppressor by directly targeting integrin β1, a key regulator of cancer cell metastasis. miR-6126 mimic treatment of cancer cells resulted in increased miR-6126 and decreased integrin β1 mRNA levels in the exosome. Functional analysis showed that treatment of endothelial cells with miR-6126 mimic significantly reduced tube formation as well as invasion and migration capacities of ovarian cancer cells in vitro. Administration of miR-6126 mimic in an orthotopic mouse model of ovarian cancer elicited a relative reduction in tumor growth, proliferating cells and microvessel density. miR-6126 inhibition promoted oncogenic behavior by leading ovarian cancer cells to release more exosomes. Our findings provide new insights into the role of exosomal miRNA-mediated tumor progression and suggest a new therapeutic approach to disrupt oncogenic phenotypes in tumors. PMID:27742688

Reconstituting redox active centers of heme-containing proteins with biomineralized gold toward peroxidase mimics with strong intrinsic catalysis and electrocatalysis for H2O2 detection.

PubMed

Zhang, Liyan; Li, Shuai; Dong, Minmin; Jiang, Yao; Li, Ru; Zhang, Shuo; Lv, Xiaoxia; Chen, Lijun; Wang, Hua

2017-01-15

A facile and efficient enzymatic reconstitution methodology has been proposed for high-catalysis peroxidase mimics by remolding the redox active centers of heme-containing proteins with the in-site biomineralized gold using hemoglobin (Hb) as a model. Catalytic hemin (Hem) was extracted from the active centers of Hb for the gold biomineralization and then reconstituted into apoHb to yield the Hem-Au@apoHb nanocomposites showing dramatically improved intrinsic catalysis and electrocatalysis over natural Hb and Hem. The biomineralized gold, on the one hand, would act as "nanowires" to promote the electron transferring of the nanocomposites. On the other hand, it would create a reactivity pathway to pre-organize and accumulate more substrates towards the active sites of the peroxidase mimics. Steady-state kinetics studies indicate that Hem-Au@apoHb could present much higher substrate affinity (lower Michaelis constants) and intrinsic catalysis even than some natural peroxidases. Moreover, the application feasibility of the prepared artificial enzymes was demonstrated by colorimetric assays and direct electrocatalysis for H 2 O 2 sensing, showing a detection limitation low as 0.45μM. Importantly, such a catalysis active-center reconstitution protocol may circumvent the substantial improvement of the intrinsic catalysis and electrocatalysis of diverse heme-containing proteins or enyzmes toward the extensive applications in the chemical, enviromental, and biomedical catalysis fields. Copyright © 2016 Elsevier B.V. All rights reserved.

The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro

PubMed Central

Serfiotis-Mitsa, Dimitra; Herbert, Andrew P.; Roberts, Gareth A.; Soares, Dinesh C.; White, John H.; Blakely, Garry W.; Uhrín, Dušan; Dryden, David T. F.

2010-01-01

Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic. PMID:20007596

Functional Somatic Symptoms Across Cultures: Perceptual and Health Care Issues.

PubMed

Löwe, Bernd; Gerloff, Christian

2018-06-01

Functional neurological disorders are conceptualized as patterns of neurological symptoms that cannot be attributed to a clear organic etiology. The study by Wilkins et al. in this issue of Psychosomatic Medicine reveals that 8.2% of patients who were initially presented with suspected stroke were later diagnosed with functional disorders, i.e., "functional stroke mimics." However, the percentage of functional stroke mimics varied substantially with patients' nationality, age, and sex. In this editorial comment, we discuss potential reasons for the intercultural variation of the frequency of functional stroke mimics.The current models of symptom perception, in which symptom perception is guided by top-down processes of the central nervous system, are helpful in explaining the intercultural variation of functional symptoms. According to these models, cultural beliefs, previous illnesses, and stressful life situations influence patients' expectations, sensory input, and finally the perception of somatic symptoms. In addition, differences in insurance status, health literacy, and health care experiences are strong predictors of health care use in patients who experience somatic symptoms.This article provides a conceptual model that integrates sociocultural factors with symptom perception and health care use relevant to the different rates of functional somatic symptoms in emergency departments across nationalities. Considering these factors, future attempts to improve care for patients with functional disorders should enhance access to effective treatment for all patient groups, empower patients through education and early participation in the treatment process, and foster interdisciplinary collaboration among specialists from somatic and mental health disciplines.

A Multiple Indicators Multiple Causes (MIMIC) model of internal barriers to drug treatment in China.

PubMed

Qi, Chang; Kelly, Brian C; Liao, Yanhui; He, Haoyu; Luo, Tao; Deng, Huiqiong; Liu, Tieqiao; Hao, Wei; Wang, Jichuan

2015-03-01

Although evidence exists for distinct barriers to drug abuse treatment (BDATs), investigations of their inter-relationships and the effect of individual characteristics on the barrier factors have been sparse, especially in China. A Multiple Indicators Multiple Causes (MIMIC) model is applied for this target. A sample of 262 drug users were recruited from three drug rehabilitation centers in Hunan Province, China. We applied a MIMIC approach to investigate the effect of gender, age, marital status, education, primary substance use, duration of primary drug use, and drug treatment experience on the internal barrier factors: absence of problem (AP), negative social support (NSS), fear of treatment (FT), and privacy concerns (PC). Drug users of various characteristics were found to report different internal barrier factors. Younger participants were more likely to report NSS (-0.19, p=0.038) and PC (-0.31, p<0.001). Compared to other drug users, ice users were more likely to report AP (0.44, p<0.001) and NSS (0.25, p=0.010). Drug treatment experiences related to AP (0.20, p=0.012). In addition, differential item functioning (DIF) occurred in three items when participant from groups with different duration of drug use, ice use, or marital status. Individual characteristics had significant effects on internal barriers to drug treatment. On this basis, BDAT perceived by different individuals could be assessed before tactics were utilized to successfully remove perceived barriers to drug treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells

PubMed Central

Pickard, Mark R.; Williams, Gwyn T.

2016-01-01

Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and –insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies. PMID:26862727

Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides ☆

PubMed Central

Lee, Michelle W.; Chakraborty, Saswata; Schmidt, Nathan W.; Murgai, Rajan; Gellman, Samuel H.; Wong, Gerard C.L.

2015-01-01

Novel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. PMID:24743021

A direct biocombinatorial strategy toward next generation, mussel-glue inspired saltwater adhesives.

PubMed

Wilke, Patrick; Helfricht, Nicolas; Mark, Andreas; Papastavrou, Georg; Faivre, Damien; Börner, Hans G

2014-09-10

Biological materials exhibit remarkable, purpose-adapted properties that provide a source of inspiration for designing new materials to meet the requirements of future applications. For instance, marine mussels are able to attach to a broad spectrum of hard surfaces under hostile conditions. Controlling wet-adhesion of synthetic macromolecules by analogue processes promises to strongly impact materials sciences by offering advanced coatings, adhesives, and glues. The de novo design of macromolecules to mimic complex aspects of mussel adhesion still constitutes a challenge. Phage display allows material scientists to design specifically interacting molecules with tailored affinity to material surfaces. Here, we report on the integration of enzymatic processing steps into phage display biopanning to expand the biocombinatorial procedure and enable the direct selection of enzymatically activable peptide adhesion domains. Adsorption isotherms and single molecule force spectroscopy show that those de novo peptides mimic complex aspects of bioadhesion, such as enzymatic activation (by tyrosinase), the switchability from weak to strong binders, and adsorption under hostile saltwater conditions. Furthermore, peptide-poly(ethylene oxide) conjugates are synthesized to generate protective coatings, which possess anti-fouling properties and suppress irreversible interactions with blood-plasma protein cocktails. The extended phage display procedure provides a generic way to non-natural peptide adhesion domains, which not only mimic nature but also improve biological sequence sections extractable from mussel-glue proteins. The de novo peptides manage to combine several tasks in a minimal 12-mer sequence and thus pave the way to overcome major challenges of technical wet glues.

Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

PubMed Central

Miras, A D; le Roux, C W

2014-01-01

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals. PMID:24213310

Estimating dermal transfer from PCB-contaminated porous surfaces.

PubMed

Slayton, T M; Valberg, P A; Wait, A D

1998-06-01

Health risks posed by dermal contact with PCB-contaminated porous surfaces have not been directly demonstrated and are difficult to estimate indirectly. Surface contamination by organic compounds is commonly assessed by collecting wipe samples with hexane as the solvent. However, for porous surfaces, hexane wipe characterization is of limited direct use when estimating potential human exposure. Particularly for porous surfaces, the relationship between the amount of organic material collected by hexane and the amount actually picked up by, for example, a person's hand touch is unknown. To better mimic PCB pickup by casual hand contact with contaminated concrete surfaces, we used alternate solvents and wipe application methods that more closely mimic casual dermal contact. Our sampling results were compared to PCB pickup using hexane-wetted wipes and the standard rubbing protocol. Dry and oil-wetted samples, applied without rubbing, picked up less than 1% of the PCBs picked up by the standard hexane procedure; with rubbing, they picked up about 2%. Without rubbing, saline-wetted wipes picked up 2.5%; with rubbing, they picked up about 12%. While the nature of dermal contact with a contaminated surface cannot be perfectly reproduced with a wipe sample, our results with alternate wiping solvents and rubbing methods more closely mimic hand contact than the standard hexane wipe protocol. The relative pickup estimates presented in this paper can be used in conjunction with site-specific PCB hexane wipe results to estimate dermal pickup rates at sites with PCB-contaminated concrete.

Potentiation of a functional autoantibody in narcolepsy by a cholinesterase inhibitor.

PubMed

Jackson, Michael W; Spencer, Nicolas J; Reed, Joanne H; Smith, Anthony J F; Gordon, Tom P

2009-12-01

We have recently reported the presence of an immunoglobulin G (IgG) autoantibody (Ab) in patients with narcolepsy with cataplexy that abolishes spontaneous colonic migrating motor complexes (CMMCs) and increases smooth muscle tension and atropine-sensitive phasic contractions in a physiological assay of an isolated colon. In this study, we used the cholinesterase inhibitor, neostigmine, to explore the mechanism of the narcoleptic IgG-mediated disruption of enteric motor function in four patients with narcolepsy with cataplexy and to identify a pharmacological mimic of the Ab. Neostigmine potentiated the narcoleptic IgG-mediated increase in smooth muscle resting tension and phasic smooth muscle contractions by an atropine-sensitive mechanism but exerted no effect on resting tension in the presence of control IgG. Decreased frequency of CMMCs mediated by IgG with anti-M3R activity was reversed by neostigmine. Therefore, a challenge with a cholinesterase inhibitor improves the specificity of the CMMC assay for narcoleptic IgG. Tetrodotoxin (TTX), a neuronal sodium channel blocker, also abolished CMMCs and increased resting tone, and a similar potentiation was observed with neostigmine; thus, TTX is a mimic of the functional effects of the narcoleptic IgG in this bioassay. These findings provide a link to pharmacological studies of canine narcolepsy and are consistent with a functional blockade of both excitatory and inhibitory motor neurons by the narcoleptic Ab, similar to the TTX mimic, presumably by binding to an autoantigenic target expressed in both populations of neurons.

3D in vitro technology for drug discovery.

PubMed

Hosseinkhani, Hossein

2012-02-01

Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure and function in vivo, will be of great benefit for a variety of biological applications from basic biology to toxicity testing and drug discovery. There have been several attempts to generate 3D tissue models but most of these models require costly equipment, and the most serious disadvantage in them is that they are too far from the mature human organs in vivo. Because of these problems, research and development in drug discovery, toxicity testing and biotech industries are highly expensive, and involve sacrifice of countless animals and it takes several years to bring a single drug/product to the market or to find the toxicity or otherwise of chemical entities. Our group has been actively working on several alternative models by merging biomaterials science, nanotechnology and biological principles to generate 3D in vitro living organs, to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to reduce animal testing and clinical trials. We have fabricated a novel type of mechanically and biologically bio-mimicking collagen-based hydrogel that would provide for interconnected mini-wells in which 3D cell/organ culture of human samples in a manner similar to human organs with extracellular matrix (ECM) molecules would be possible. These products mimic the physical, chemical, and biological properties of natural organs and tissues at different scales. This paper will review the outcome of our several experiments so far in this direction and the future perspectives.

Crying wolf to a predator: deceptive vocal mimicry by a bird protecting young

PubMed Central

Igic, Branislav; McLachlan, Jessica; Lehtinen, Inkeri; Magrath, Robert D.

2015-01-01

Animals often mimic dangerous or toxic species to deter predators; however, mimicry of such species may not always be possible and mimicry of benign species seems unlikely to confer anti-predator benefits. We reveal a system in which a bird mimics the alarm calls of harmless species to fool a predator 40 times its size and protect its offspring against attack. Our experiments revealed that brown thornbills (Acanthiza pusilla) mimic a chorus of other species' aerial alarm calls, a cue of an Accipiter hawk in flight, when predators attack their nest. The absence of any flying predators in this context implies that these alarms convey deceptive information about the type of danger present. Experiments on the primary nest predators of thornbills, pied currawongs (Strepera graculina), revealed that the predators treat these alarms as if they themselves are threatened by flying hawks, either by scanning the sky for danger or fleeing, confirming a deceptive function. In turn, these distractions delay attack and provide thornbill nestlings with an opportunity to escape. This sophisticated defence strategy exploits the complex web of interactions among multiple species across several trophic levels, and in particular exploits a predator's ability to eavesdrop on and respond appropriately to heterospecific alarm calls. Our findings demonstrate that prey can fool predators by deceptively mimicking alarm calls of harmless species, suggesting that defensive mimicry could be more widespread because of indirect effects on predators within a web of eavesdropping. PMID:26041353

Substituted Phthalimide AC94377 Is a Selective Agonist of the Gibberellin Receptor GID11[OPEN

PubMed Central

Otani, Masato; Shimotakahara, Hiroaki; Yoon, Jung-Min; Park, Seung-Hyun; Miyaji, Tomoko; Nakano, Takeshi; Nakamura, Hidemitsu; Nakajima, Masatoshi

2017-01-01

Gibberellin (GA) is a major plant hormone that regulates plant growth and development and is widely used as a plant growth regulator in agricultural production. There is an increasing demand for function-limited GA mimics due to the limitations on the agronomical application of GA to crops, including GA’s high cost of producing and its leading to the crops’ lodging. AC94377, a substituted phthalimide, is a chemical that mimics the growth-regulating activity of GAs in various plants, despite its structural difference. Although AC94377 is widely studied in many weeds and crops, its mode of action as a GA mimic is largely unknown. In this study, we confirmed that AC94377 displays GA-like activities in Arabidopsis (Arabidopsis thaliana) and demonstrated that AC94377 binds to the Arabidopsis GIBBERELLIN INSENSITIVE DWARF1 (GID1) receptor (AtGID1), forms the AtGID1-AC94377-DELLA complex, and induces the degradation of DELLA protein. Our results also indicated that AC94377 is selective for a specific subtype among three AtGID1s and that the selectivity of AC94377 is attributable to a single residue at the entrance to the hydrophobic pocket of GID1. We conclude that AC94377 is a GID1 agonist with selectivity for a specific subtype of GID1, which could be further developed and used as a function-limited regulator of plant growth in both basic study and agriculture. PMID:27899534

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

PubMed

Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

2016-01-01

In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Antiproliferative efficacy of curcumin mimics through microtubule destabilization.

PubMed

Khwaja, Sadiya; Fatima, Kaneez; Hasanain, Mohammad; Behera, Chittaranjan; Kour, Avneet; Singh, Arjun; Luqman, Suaib; Sarkar, Jayanta; Chanda, Debabrata; Shanker, Karuna; Gupta, A K; Mondhe, D M; Negi, Arvind S

2018-05-10

Curcumin possesses an attractive chemical structure with highly conjugated diferuloylmethane core. Curcumin mimics have been designed and prepared with an additional bridged phenyl ring in conjugation. Fourteen diverse analogues were evaluated against a panel of human cancer cell lines. The best analogue of the series i.e. compound 6a exhibited potent cytotoxicity against A431, epidermoid carcinoma cell line (IC 50  = 1.5 μM) and DLD1, colorectal adenocarcinoma cell line (IC 50  = 6.9 μM). In tubulin kinetics experiment, compound 6a destabilized polymerisation process (IC 50  = 4.68 μM). In cell cycle analysis, compound 6a exerted G2/M phase arrest in A431 cells and induced apoptosis. In Ehrlich Ascites Carcinoma in Swiss-albino mice, compound 6a showed 78.6% tumour reduction at 80 mg/kg dose and 57% solid tumour reduction at 150 mg/kg dose. Further, in acute-oral toxicity experiment in rodent model, compound 6a was given in three different oral doses to Swiss albino mice. There were non-significant changes in various biochemical parameters and major body organs studied, including their absolute and relative weights. It was tolerable up to 300 mg/kg dose in Swiss-albino mice. The present study shows that the novel curcumin mimic 6a is a safe and efficacious anticancer compound. However, it needs to be optimized for better efficacy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX

DOE PAGES

Pinard, Melissa A.; Aggarwal, Mayank; Mahon, Brian P.; ...

2015-09-23

Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO 2to HCO 3 $-$, thereby playing a role in pH regulation. The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-basedmore » drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5 Å, anR cryst of 18.0% and anR free of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less