Mechanical response of common millet (Panicum miliaceum) seeds under quasi-static compression: Experiments and modeling.

Science.gov (United States)

Hasseldine, Benjamin P J; Gao, Chao; Collins, Joseph M; Jung, Hyun-Do; Jang, Tae-Sik; Song, Juha; Li, Yaning

2017-09-01

The common millet (Panicum miliaceum) seedcoat has a fascinating complex microstructure, with jigsaw puzzle-like epidermis cells articulated via wavy intercellular sutures to form a compact layer to protect the kernel inside. However, little research has been conducted on linking the microstructure details with the overall mechanical response of this interesting biological composite. To this end, an integrated experimental-numerical-analytical investigation was conducted to both characterize the microstructure and ascertain the microscale mechanical properties and to test the overall response of kernels and full seeds under macroscale quasi-static compression. Scanning electron microscopy (SEM) was utilized to examine the microstructure of the outer seedcoat and nanoindentation was performed to obtain the material properties of the seedcoat hard phase material. A multiscale computational strategy was applied to link the microstructure to the macroscale response of the seed. First, the effective anisotropic mechanical properties of the seedcoat were obtained from finite element (FE) simulations of a microscale representative volume element (RVE), which were further verified from sophisticated analytical models. Then, macroscale FE models of the individual kernel and full seed were developed. Good agreement between the compression experiments and FE simulations were obtained for both the kernel and the full seed. The results revealed the anisotropic property and the protective function of the seedcoat, and showed that the sutures of the seedcoat play an important role in transmitting and distributing loads in responding to external compression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Teaching the Common Aspects in Mechanical, Electromagnetic and Quantum Waves at Interfaces and Waveguides

Science.gov (United States)

Rojas, R.; Robles, P.

2011-01-01

We discuss common features in mechanical, electromagnetic and quantum systems, supporting identical results for the transmission and reflection coefficients of waves arriving perpendicularly at a plane interface. Also, we briefly discuss the origin of special notions such as refractive index in quantum mechanics, massive photons in wave guides and…

Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin.

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Vasyl V Mykuliak

2018-04-01

Full Text Available Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins.

Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders.

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Sgadò, Paola; Provenzano, Giovanni; Dassi, Erik; Adami, Valentina; Zunino, Giulia; Genovesi, Sacha; Casarosa, Simona; Bozzi, Yuri

2013-12-19

Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD.

An economic experiment reveals that humans prefer pool punishment to maintain the commons

Science.gov (United States)

Traulsen, Arne; Röhl, Torsten; Milinski, Manfred

2012-01-01

Punishment can stabilize costly cooperation and ensure the success of a common project that is threatened by free-riders. Punishment mechanisms can be classified into pool punishment, where the punishment act is carried out by a paid third party, (e.g. a police system or a sheriff), and peer punishment, where the punishment act is carried out by peers. Which punishment mechanism is preferred when both are concurrently available within a society? In an economic experiment, we show that the majority of subjects choose pool punishment, despite being costly even in the absence of defectors, when second-order free-riders, cooperators that do not punish, are also punished. Pool punishers are mutually enforcing their support for the punishment organization, stably trapping each other. Our experimental results show how organized punishment could have displaced individual punishment in human societies. PMID:22764167

Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

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Marcel eLevy Nogueira

2015-09-01

Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

Change is good: variations in common biological mechanisms in the epsilonproteobacterial genera Campylobacter and Helicobacter.

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Gilbreath, Jeremy J; Cody, William L; Merrell, D Scott; Hendrixson, David R

2011-03-01

Microbial evolution and subsequent species diversification enable bacterial organisms to perform common biological processes by a variety of means. The epsilonproteobacteria are a diverse class of prokaryotes that thrive in diverse habitats. Many of these environmental niches are labeled as extreme, whereas other niches include various sites within human, animal, and insect hosts. Some epsilonproteobacteria, such as Campylobacter jejuni and Helicobacter pylori, are common pathogens of humans that inhabit specific regions of the gastrointestinal tract. As such, the biological processes of pathogenic Campylobacter and Helicobacter spp. are often modeled after those of common enteric pathogens such as Salmonella spp. and Escherichia coli. While many exquisite biological mechanisms involving biochemical processes, genetic regulatory pathways, and pathogenesis of disease have been elucidated from studies of Salmonella spp. and E. coli, these paradigms often do not apply to the same processes in the epsilonproteobacteria. Instead, these bacteria often display extensive variation in common biological mechanisms relative to those of other prototypical bacteria. In this review, five biological processes of commonly studied model bacterial species are compared to those of the epsilonproteobacteria C. jejuni and H. pylori. Distinct differences in the processes of flagellar biosynthesis, DNA uptake and recombination, iron homeostasis, interaction with epithelial cells, and protein glycosylation are highlighted. Collectively, these studies support a broader view of the vast repertoire of biological mechanisms employed by bacteria and suggest that future studies of the epsilonproteobacteria will continue to provide novel and interesting information regarding prokaryotic cellular biology.

Comparative transcriptome analysis reveals the genetic basis of skin color variation in common carp.

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Yanliang Jiang

Full Text Available The common carp is an important aquaculture species that is widely distributed across the world. During the long history of carp domestication, numerous carp strains with diverse skin colors have been established. Skin color is used as a visual criterion to determine the market value of carp. However, the genetic basis of common carp skin color has not been extensively studied.In this study, we performed Illumina sequencing on two common carp strains: the reddish Xingguo red carp and the brownish-black Yellow River carp. A total of 435,348,868 reads were generated, resulting in 198,781 assembled contigs that were used as reference sequences. Comparisons of skin transcriptome files revealed 2,012 unigenes with significantly different expression in the two common carp strains, including 874 genes that were up-regulated in Xingguo red carp and 1,138 genes that were up-regulated in Yellow River carp. The expression patterns of 20 randomly selected differentially expressed genes were validated using quantitative RT-PCR. Gene pathway analysis of the differentially expressed genes indicated that melanin biosynthesis, along with the Wnt and MAPK signaling pathways, is highly likely to affect the skin pigmentation process. Several key genes involved in the skin pigmentation process, including TYRP1, SILV, ASIP and xCT, showed significant differences in their expression patterns between the two strains.In this study, we conducted a comparative transcriptome analysis of Xingguo red carp and Yellow River carp skins, and we detected key genes involved in the common carp skin pigmentation process. We propose that common carp skin pigmentation depends upon at least three pathways. Understanding fish skin color genetics will facilitate future molecular selection of the fish skin colors with high market values.

Comparative transcriptome analysis reveals the genetic basis of skin color variation in common carp.

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Jiang, Yanliang; Zhang, Songhao; Xu, Jian; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A; Sun, Xiaowen; Xu, Peng

2014-01-01

The common carp is an important aquaculture species that is widely distributed across the world. During the long history of carp domestication, numerous carp strains with diverse skin colors have been established. Skin color is used as a visual criterion to determine the market value of carp. However, the genetic basis of common carp skin color has not been extensively studied. In this study, we performed Illumina sequencing on two common carp strains: the reddish Xingguo red carp and the brownish-black Yellow River carp. A total of 435,348,868 reads were generated, resulting in 198,781 assembled contigs that were used as reference sequences. Comparisons of skin transcriptome files revealed 2,012 unigenes with significantly different expression in the two common carp strains, including 874 genes that were up-regulated in Xingguo red carp and 1,138 genes that were up-regulated in Yellow River carp. The expression patterns of 20 randomly selected differentially expressed genes were validated using quantitative RT-PCR. Gene pathway analysis of the differentially expressed genes indicated that melanin biosynthesis, along with the Wnt and MAPK signaling pathways, is highly likely to affect the skin pigmentation process. Several key genes involved in the skin pigmentation process, including TYRP1, SILV, ASIP and xCT, showed significant differences in their expression patterns between the two strains. In this study, we conducted a comparative transcriptome analysis of Xingguo red carp and Yellow River carp skins, and we detected key genes involved in the common carp skin pigmentation process. We propose that common carp skin pigmentation depends upon at least three pathways. Understanding fish skin color genetics will facilitate future molecular selection of the fish skin colors with high market values.

Characteristic Features of the Exotic Superconductors: Evidence for a Common Pairing Mechanism

International Nuclear Information System (INIS)

Brandow, B.

1999-01-01

We report on a comprehensive examination of the exotic superconductors (the materials so-labelled by Uemura and co-workers), to determine as far as possible the true systematics among their many anomalous features. In the crystal-chemistry aspects as well as in the electronic properties, we find features which appear to be universal for these materials, and also features which are clearly not universal but which are common enough to be considered typical for these materials. A number of implications are presented. It appears that all of these materials are sharing some ''new'' pairing mechanism, usually in addition to the conventional phonon mechanism

Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors

DEFF Research Database (Denmark)

Olsen, Jeppe A; Ahring, Philip K; Kastrup, Jette Sandholm Jensen

2014-01-01

Modulation of Cys loop receptor ion channels is a proven drug discovery strategy, but many underlying mechanisms of the mode of action are poorly understood. We report the x-ray structure of the acetylcholine-binding protein from Lymnaea stagnalis with NS9283, a stoichiometry selective positive...... on efficacy. The shared modulatory profile along with a binding site located in an extracellular subunit interface suggest that modulation via an agonist-like mechanism may be a common mechanism of action that potentially could apply to Cys loop receptors beyond the α4β2 nAChRs....... modulator that targets the α4-α4 interface of α4β2 nicotinic acetylcholine receptors (nAChRs). Together with homology modeling, mutational data, quantum mechanical calculations, and pharmacological studies on α4β2 nAChRs, the structure reveals a modulator binding mode that overlaps the α4-α4 interface...

Audits reveal ten common environmental problems

International Nuclear Information System (INIS)

Buys, M.W.

1992-01-01

The old saying that open-quotes an ounce of prevention is worth a pound of cureclose quotes rings particularly true in environmental matters in the 1990s. Environmental problems can potentially lead to expensive fines, costly cleanups, negative public relations, and even criminal sanctions against members of the corporation. A recurring pattern of problems has been noted during the performance of environmental disposition, acquisition, and compliance assessments of many different operators in most of the producing states. The ten most common problems found in oilfield audits are discussed here in an effort to enhance the awareness of operators

Transcriptome analysis reveals the time of the fourth round of genome duplication in common carp (Cyprinus carpio)

Science.gov (United States)

2012-01-01

Background Common carp (Cyprinus carpio) is thought to have undergone one extra round of genome duplication compared to zebrafish. Transcriptome analysis has been used to study the existence and timing of genome duplication in species for which genome sequences are incomplete. Large-scale transcriptome data for the common carp genome should help reveal the timing of the additional duplication event. Results We have sequenced the transcriptome of common carp using 454 pyrosequencing. After assembling the 454 contigs and the published common carp sequences together, we obtained 49,669 contigs and identified genes using homology searches and an ab initio method. We identified 4,651 orthologous pairs between common carp and zebrafish and found 129,984 paralogous pairs within the common carp. An estimation of the synonymous substitution rate in the orthologous pairs indicated that common carp and zebrafish diverged 120 million years ago (MYA). We identified one round of genome duplication in common carp and estimated that it had occurred 5.6 to 11.3 MYA. In zebrafish, no genome duplication event after speciation was observed, suggesting that, compared to zebrafish, common carp had undergone an additional genome duplication event. We annotated the common carp contigs with Gene Ontology terms and KEGG pathways. Compared with zebrafish gene annotations, we found that a set of biological processes and pathways were enriched in common carp. Conclusions The assembled contigs helped us to estimate the time of the fourth-round of genome duplication in common carp. The resource that we have built as part of this study will help advance functional genomics and genome annotation studies in the future. PMID:22424280

Common Factor Mechanisms in Clinical Practice and Their Relationship with Outcome.

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Gaitan-Sierra, Carolina; Hyland, Michael E

2015-01-01

This study investigates three common factor mechanisms that could affect outcome in clinical practice: response expectancy, the affective expectation model and motivational concordance. Clients attending a gestalt therapy clinic (30 clients), a sophrology (therapeutic technique) clinic (33 clients) and a homeopathy clinic (31 clients) completed measures of expectancy and the Positive Affect and Negative Affect Schedule (PANAS) before their first session. After 1 month, they completed PANAS and measures of intrinsic motivation, perceived effort and empowerment. Expectancy was not associated with better outcome and was no different between treatments. Although some of the 54 clients who endorsed highest expectations showed substantial improvement, others did not: 19 had no change or deteriorated in positive affect, and 18 had the same result for negative affect. Intrinsic motivation independently predicted changes in negative affect (β = -0.23). Intrinsic motivation (β = 0.24), effort (β = 0.23) and empowerment (β = 0.20) independently predicted positive affect change. Expectancy (β = -0.17) negatively affected changes in positive affect. Clients found gestalt and sophrology to be more intrinsically motivating, empowering and effortful compared with homeopathy. Greater improvement in mood was found for sophrology and gestalt than for homeopathy clients. These findings are inconsistent with response expectancy as a common factor mechanism in clinical practice. The results support motivational concordance (outcome influenced by the intrinsic enjoyment of the therapy) and the affective expectation model (high expectations can lead for some clients to worse outcome). When expectancy correlates with outcome in some other studies, this may be due to confound between expectancy and intrinsic enjoyment. Common factors play an important role in outcome. Intrinsic enjoyment of a therapeutic treatment is associated with better outcome. Active engagement with a

Revealing vilazodone's binding mechanism underlying its partial agonism to the 5-HT1A receptor in the treatment of major depressive disorder.

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Zheng, Guoxun; Xue, Weiwei; Yang, Fengyuan; Zhang, Yang; Chen, Yuzong; Yao, Xiaojun; Zhu, Feng

2017-11-01

It has been estimated that major depressive disorder (MDD) will become the second largest global burden among all diseases by 2030. Various types of drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonin receptor partial agonist/reuptake inhibitors (SPARIs), have been approved and become the primary or first-line medications prescribed for MDD. SPARI was expected to demonstrate more enhanced drug efficacy and a rapid onset of action as compared to SSRI and SNRI. As one of the most famous SPARIs, vilazodone was approved by the FDA for the treatment of MDD. Because of the great clinical importance of vilazodone, its binding mechanism underlying its partial agonism to the 5-HT 1A receptor (5-HT 1A R) could provide valuable information to SPARIs' drug-like properties. However, this mechanism has not been reported to date; consequently, the rational design of new efficacious SPARI-based MDD drugs is severely hampered. To explore the molecular mechanism of vilazodone, an integrated computational strategy was adopted in this study to reveal its binding mechanism and prospective structural feature at the agonist binding site of 5-HT 1A R. As a result, 22 residues of this receptor were identified as hotspots, consistently favoring the binding of vilazodone and its analogues, and a common binding mechanism underlying their partial agonism to 5-HT 1A R was, therefore, discovered. Moreover, three main interaction features between vilazodone and 5-HT 1A R have been revealed and schematically summarized. In summary, this newly identified binding mechanism will provide valuable information for medicinal chemists working in the field of rational design of novel SPARIs for MDD treatment.

MECHANISM TRANSFER PRICING AND THE NEED INTRODUCTION COMMON CONSOLIDATED CORPORATE INCOME TAX TRANSNATIONAL

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Gheorghe Grigorescu

2013-06-01

Full Text Available Transfer pricing mechanism is a tool commonly used to transfer the tax base in countries with high tax countries with lower taxation. In the European Union the financial operations generate tax revenue losses. In an attempt to limit manipulation by corporate tax systems, many public authorities have introduced transfer pricing rules, but these rules has shown limited efficacy, however, contribute to the increasing complexity of tax laws and the emergence of additional costs for companies. This paper deals with the concrete examples, the solution to solving the problem of transfer pricing in the European Union by the introduction of common consolidated corporate income tax.

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

International Nuclear Information System (INIS)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures

Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. I. Common molecular mechanisms

Energy Technology Data Exchange (ETDEWEB)

Borg, D.C.

1984-01-01

Some aspects of molecular mechanisms common to radiation and chemical carcinogenesis are discussed, particularly the DNA damage done by these agents. Emphasis is placed on epidemiological considerations and on dose-response models used in risk assessment to extrapolate from experimental data obtained at high doses to the effects from long-term, low-level exposures. 3 references, 6 figures. (ACR)

Measures and mechanisms of common ground: backchannels, conversational repair, and interactive alignmentin free and task-oriented social interactions

DEFF Research Database (Denmark)

Fusaroli, Riccardo; Tylén, Kristian; Madsen, Katrine Garly

A crucial aspect of everyday conversational interactions is our ability to establish and maintain common ground. Understanding the relevant mechanisms involved in such social coordination remains an important challenge for cognitive science. While common ground is often discussed in very general ...

Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators

Science.gov (United States)

Hubbard, Basil P.; Gomes, Ana P.; Dai, Han; Li, Jun; Case, April W.; Considine, Thomas; Riera, Thomas V.; Lee, Jessica E.; Sook Yen, E; Lamming, Dudley W.; Pentelute, Bradley L.; Schuman, Eli R.; Stevens, Linda A.; Ling, Alvin J. Y.; Armour, Sean M.; Michan, Shaday; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M.; Blum, Charles A.; Disch, Jeremy S.; Ng, Pui Yee; Howitz, Konrad T.; Rolo, Anabela P.; Hamuro, Yoshitomo; Moss, Joel; Perni, Robert B.; Ellis, James L.; Vlasuk, George P.; Sinclair, David A.

2013-01-01

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu230, located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs. PMID:23471411

Evidence for a common mechanism of SIRT1 regulation by allosteric activators.

Science.gov (United States)

Hubbard, Basil P; Gomes, Ana P; Dai, Han; Li, Jun; Case, April W; Considine, Thomas; Riera, Thomas V; Lee, Jessica E; E, Sook Yen; Lamming, Dudley W; Pentelute, Bradley L; Schuman, Eli R; Stevens, Linda A; Ling, Alvin J Y; Armour, Sean M; Michan, Shaday; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M; Blum, Charles A; Disch, Jeremy S; Ng, Pui Yee; Howitz, Konrad T; Rolo, Anabela P; Hamuro, Yoshitomo; Moss, Joel; Perni, Robert B; Ellis, James L; Vlasuk, George P; Sinclair, David A

2013-03-08

A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1α and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.

Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

Science.gov (United States)

Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

2013-01-01

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

Energy Technology Data Exchange (ETDEWEB)

Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

2011-10-15

All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

Directory of Open Access Journals (Sweden)

Peter A. Bell

2013-06-01

Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

Science.gov (United States)

Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R

2013-06-18

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Integrative modelling reveals mechanisms linking productivity and plant species richness.

Science.gov (United States)

Grace, James B; Anderson, T Michael; Seabloom, Eric W; Borer, Elizabeth T; Adler, Peter B; Harpole, W Stanley; Hautier, Yann; Hillebrand, Helmut; Lind, Eric M; Pärtel, Meelis; Bakker, Jonathan D; Buckley, Yvonne M; Crawley, Michael J; Damschen, Ellen I; Davies, Kendi F; Fay, Philip A; Firn, Jennifer; Gruner, Daniel S; Hector, Andy; Knops, Johannes M H; MacDougall, Andrew S; Melbourne, Brett A; Morgan, John W; Orrock, John L; Prober, Suzanne M; Smith, Melinda D

2016-01-21

How ecosystem productivity and species richness are interrelated is one of the most debated subjects in the history of ecology. Decades of intensive study have yet to discern the actual mechanisms behind observed global patterns. Here, by integrating the predictions from multiple theories into a single model and using data from 1,126 grassland plots spanning five continents, we detect the clear signals of numerous underlying mechanisms linking productivity and richness. We find that an integrative model has substantially higher explanatory power than traditional bivariate analyses. In addition, the specific results unveil several surprising findings that conflict with classical models. These include the isolation of a strong and consistent enhancement of productivity by richness, an effect in striking contrast with superficial data patterns. Also revealed is a consistent importance of competition across the full range of productivity values, in direct conflict with some (but not all) proposed models. The promotion of local richness by macroecological gradients in climatic favourability, generally seen as a competing hypothesis, is also found to be important in our analysis. The results demonstrate that an integrative modelling approach leads to a major advance in our ability to discern the underlying processes operating in ecological systems.

The effects of common footwear on stance-phase mechanical properties of the prosthetic foot-shoe system.

Science.gov (United States)

Major, Matthew J; Scham, Joel; Orendurff, Michael

2018-04-01

Prosthetic feet are prescribed based on their mechanical function and user functional level. Subtle changes to the stiffness and hysteresis of heel, midfoot, and forefoot regions can influence the dynamics and economy of gait in prosthesis users. However, the user's choice of shoes may alter the prosthetic foot-shoe system mechanical characteristics, compromising carefully prescribed and rigorously engineered performance of feet. Observe the effects of footwear on the mechanical properties of the prosthetic foot-shoe system including commonly prescribed prosthetic feet. Repeated-measures, Mechanical characterization. The stiffness and energy return was measured using a hydraulic-driven materials test machine across combinations of five prosthetic feet and four common shoes as well as a barefoot condition. Heel energy return decreased by an average 4%-9% across feet in all shoes compared to barefoot, with a cushioned trainer displaying the greatest effect. Foot designs that may improve perceived stability by providing low heel stiffness and rapid foot-flat were compromised by the addition of shoes. Shoes altered prosthesis mechanical characteristics in the sagittal and frontal planes, suggesting that shoe type should be controlled or reported in research comparing prostheses. Understanding of how different shoes could alter certain gait-related characteristics of prostheses may aid decisions on footwear made by clinicians and prosthesis users. Clinical relevance Shoes can alter function of the prosthetic foot-shoe system in unexpected and sometimes undesirable ways, often causing similar behavior across setups despite differences in foot design, and prescribing clinicians should carefully consider these effects on prosthesis performance.

Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation

Science.gov (United States)

Meng, Guoyu; Spahich, Nicole; Kenjale, Roma; Waksman, Gabriel; St Geme, Joseph W

2011-01-01

Bacterial biofilms are complex microbial communities that are common in nature and are being recognized increasingly as an important determinant of bacterial virulence. However, the structural determinants of bacterial aggregation and eventual biofilm formation have been poorly defined. In Gram-negative bacteria, a major subgroup of extracellular proteins called self-associating autotransporters (SAATs) can mediate cell–cell adhesion and facilitate biofilm formation. In this study, we used the Haemophilus influenzae Hap autotransporter as a prototype SAAT to understand how bacteria associate with each other. The crystal structure of the H. influenzae HapS passenger domain (harbouring the SAAT domain) was determined to 2.2 Å by X-ray crystallography, revealing an unprecedented intercellular oligomerization mechanism for cell–cell interaction. The C-terminal SAAT domain folds into a triangular-prism-like structure that can mediate Hap–Hap dimerization and higher degrees of multimerization through its F1–F2 edge and F2 face. The intercellular multimerization can give rise to massive buried surfaces that are required for overcoming the repulsive force between cells, leading to bacterial cell–cell interaction and formation of complex microcolonies. PMID:21841773

Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

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Cassandra Collins

2017-09-01

Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

Opto-acoustic microscopy reveals adhesion mechanics of single cells

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Abi Ghanem, Maroun; Dehoux, Thomas; Liu, Liwang; Le Saux, Guillaume; Plawinski, Laurent; Durrieu, Marie-Christine; Audoin, Bertrand

2018-01-01

Laser-generated GHz-ultrasonic-based technologies have shown the ability to image single cell adhesion and stiffness simultaneously. Using this new modality, we here demonstrate quantitative indicators to investigate contact mechanics and adhesion processes of the cell. We cultured human cells on a rigid substrate, and we used an inverted pulsed opto-acoustic microscope to generate acoustic pulses containing frequencies up to 100 GHz in the substrate. We map the reflection of the acoustic pulses at the cell-substrate interface to obtain images of the acoustic impedance of the cell, Zc, as well as of the stiffness of the interface, K, with 1 μm lateral resolution. Our results show that the standard deviation ΔZc reveals differences between different cell types arising from the multiplicity of local conformations within the nucleus. From the distribution of K-values within the nuclear region, we extract a mean interfacial stiffness, Km, that quantifies the average contact force in areas of the cell displaying weak bonding. By analogy with classical contact mechanics, we also define the ratio of the real to nominal contact areas, Sr/St. We show that Km can be interpreted as a quantitative indicator of passive contact at metal-cell interfaces, while Sr/St is sensitive to active adhesive processes in the nuclear region. The ability to separate the contributions of passive and active adhesion processes should allow gaining insight into cell-substrate interactions, with important applications in tissue engineering.

Divergent regeneration-competent cells adopt a common mechanism for callus initiation in angiosperms.

Science.gov (United States)

Hu, Bo; Zhang, Guifang; Liu, Wu; Shi, Jianmin; Wang, Hua; Qi, Meifang; Li, Jiqin; Qin, Peng; Ruan, Ying; Huang, Hai; Zhang, Yijing; Xu, Lin

2017-06-01

In tissue culture, the formation of callus from detached explants is a key step in plant regeneration; however, the regenerative abilities in different species are variable. While nearly all parts of organs of the dicot Arabidopsis thaliana are ready for callus formation, mature regions of organs in monocot rice ( Oryza sativa ) and other cereals are extremely unresponsive to tissue culture. Whether there is a common molecular mechanism beyond these different regenerative phenomena is unclear. Here we show that the Arabidopsis and rice use different regeneration-competent cells to initiate callus, whereas the cells all adopt WUSCHEL-RELATED HOMEOBOX 11 ( WOX11 ) and WOX5 during cell fate transition. Different from Arabidopsis which maintains regeneration-competent cells in mature organs, rice exhausts those cells during organ maturation, resulting in regenerative inability in mature organs. Our study not only explains this old perplexity in agricultural biotechnology, but also provides common molecular markers for tissue culture of different angiosperm species.

On the common mechanism for initiation of different effects of low doses of ionizing radiations

International Nuclear Information System (INIS)

Ehjdus, L.Kh.

1996-01-01

Main regularities of different endpoints of ionizing radiation low dose effects (adaptive response, stimulation of proliferation, special radiosensitivity of lymphoid cells, and others) have been examined. It has been shown that these endpoints have a commonness for the dose interval, the shape of the dose-response curve, the reverse effect of dose rate, non-specificity toward initiating agents, and others. An explanation is suggested for the common mechanism of the initiation of all the studied low dose effects, basing on the theory of the non-specific reaction of cell to external influences. It is concluded that initiation of the low dose effects is conditioned by radiation induced damage of functions of plasmic and internal membranes

Opto-acoustic microscopy reveals adhesion mechanics of single cells.

Science.gov (United States)

Abi Ghanem, Maroun; Dehoux, Thomas; Liu, Liwang; Le Saux, Guillaume; Plawinski, Laurent; Durrieu, Marie-Christine; Audoin, Bertrand

2018-01-01

Laser-generated GHz-ultrasonic-based technologies have shown the ability to image single cell adhesion and stiffness simultaneously. Using this new modality, we here demonstrate quantitative indicators to investigate contact mechanics and adhesion processes of the cell. We cultured human cells on a rigid substrate, and we used an inverted pulsed opto-acoustic microscope to generate acoustic pulses containing frequencies up to 100 GHz in the substrate. We map the reflection of the acoustic pulses at the cell-substrate interface to obtain images of the acoustic impedance of the cell, Z c , as well as of the stiffness of the interface, K, with 1 μm lateral resolution. Our results show that the standard deviation ΔZ c reveals differences between different cell types arising from the multiplicity of local conformations within the nucleus. From the distribution of K-values within the nuclear region, we extract a mean interfacial stiffness, K m , that quantifies the average contact force in areas of the cell displaying weak bonding. By analogy with classical contact mechanics, we also define the ratio of the real to nominal contact areas, S r /S t . We show that K m can be interpreted as a quantitative indicator of passive contact at metal-cell interfaces, while S r /S t is sensitive to active adhesive processes in the nuclear region. The ability to separate the contributions of passive and active adhesion processes should allow gaining insight into cell-substrate interactions, with important applications in tissue engineering.

Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

Science.gov (United States)

Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

2016-07-01

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

Phaseolin expression in tobacco chloroplast reveals an autoregulatory mechanism in heterologous protein translation.

Science.gov (United States)

De Marchis, Francesca; Bellucci, Michele; Pompa, Andrea

2016-02-01

Plastid DNA engineering is a well-established research area of plant biotechnology, and plastid transgenes often give high expression levels. However, it is still almost impossible to predict the accumulation rate of heterologous protein in transplastomic plants, and there are many cases of unsuccessful transgene expression. Chloroplasts regulate their proteome at the post-transcriptional level, mainly through translation control. One of the mechanisms to modulate the translation has been described in plant chloroplasts for the chloroplast-encoded subunits of multiprotein complexes, and the autoregulation of the translation initiation of these subunits depends on the availability of their assembly partners [control by epistasy of synthesis (CES)]. In Chlamydomonas reinhardtii, autoregulation of endogenous proteins recruited in the assembly of functional complexes has also been reported. In this study, we revealed a self-regulation mechanism triggered by the accumulation of a soluble recombinant protein, phaseolin, in the stroma of chloroplast-transformed tobacco plants. Immunoblotting experiments showed that phaseolin could avoid this self-regulation mechanism when targeted to the thylakoids in transplastomic plants. To inhibit the thylakoid-targeted phaseolin translation as well, this protein was expressed in the presence of a nuclear version of the phaseolin gene with a transit peptide. Pulse-chase and polysome analysis revealed that phaseolin mRNA translation on plastid ribosomes was repressed due to the accumulation in the stroma of the same soluble polypeptide imported from the cytosol. We suggest that translation autoregulation in chloroplast is not limited to heteromeric protein subunits but also involves at least some of the foreign soluble recombinant proteins, leading to the inhibition of plastome-encoded transgene expression in chloroplast. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.

Science.gov (United States)

Ismail, Hanafy M; Barton, Victoria E; Panchana, Matthew; Charoensutthivarakul, Sitthivut; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

2016-05-23

In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.

Common and distinct neural mechanisms of attentional switching and response conflict.

Science.gov (United States)

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2012-08-21

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

Directory of Open Access Journals (Sweden)

Michael Schnoor

2015-01-01

Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

Mechanism of the Glycosidic Bond Cleavage of Mismatched Thymine in Human Thymine DNA Glycosylase Revealed by Classical Molecular Dynamics and Quantum Mechanical/Molecular Mechanical Calculations.

Science.gov (United States)

Kanaan, Natalia; Crehuet, Ramon; Imhof, Petra

2015-09-24

Base excision of mismatched or damaged nucleotides catalyzed by glycosylase enzymes is the first step of the base excision repair system, a machinery preserving the integrity of DNA. Thymine DNA glycosylase recognizes and removes mismatched thymine by cleaving the C1'-N1 bond between the base and the sugar ring. Our quantum mechanical/molecular mechanical calculations of this reaction in human thymine DNA glycosylase reveal a requirement for a positive charge in the active site to facilitate C1'-N1 bond scission: protonation of His151 significantly lowers the free energy barrier for C1'-N1 bond dissociation compared to the situation with neutral His151. Shuttling a proton from His151 to the thymine base further reduces the activation free energy for glycosidic bond cleavage. Classical molecular dynamics simulations of the H151A mutant suggest that the mutation to the smaller, neutral, residue increases the water accessibility of the thymine base, rendering direct proton transfer from the bulk feasible. Quantum mechanical/molecular mechanical calculations of the glycosidic bond cleavage reaction in the H151A mutant show that the activation free energy is slightly lower than in the wild-type enzyme, explaining the experimentally observed higher reaction rates in this mutant.

Revealing the Interface Structure and Bonding Mechanism of Coupling Agent Treated WPC

Directory of Open Access Journals (Sweden)

Jiuping Rao

2018-03-01

Full Text Available This paper presents the interfacial optimisation of wood plastic composites (WPC based on recycled wood flour and polyethylene by employing maleated and silane coupling agents. The effect of the incorporation of the coupling agents on the variation of chemical structure of the composites were investigated by Attenuated total reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR and Solid state 13C Nuclear Magnetic Resonance spectroscopy (NMR analyses. The results revealed the chemical reactions that occurred between the coupling agents and raw materials, which thus contributed to the enhancement of compatibility and interfacial adhesion between the constituents of WPC. NMR results also indicated that there existed the transformation of crystalline cellulose to an amorphous state during the coupling agent treatments, reflecting the inferior resonance of crystalline carbohydrates. Fluorescence Microscope (FM and Scanning Electron Microscope (SEM analyses showed the improvements of wood particle dispersion and wettability, compatibility of the constituents, and resin penetration, and impregnation of the composites after the coupling agent treatments. The optimised interface of the composites was attributed to interdiffusion, electrostatic adhesion, chemical reactions, and mechanical interlocking bonding mechanisms.

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche

Energy Technology Data Exchange (ETDEWEB)

Morin, Emmanuelle; Kohler, Annegret; Baker, Adam R.; Foulongne-Oriol, Marie; Lombard, Vincent; Nagy, Laszlo G.; Ohm, Robin A.; Patyshakuliyeva, Aleksandrina; Brun, Annick; Aerts, Andrea L.; Bailey, Andrew M.; Billette, Christophe; Coutinho, Pedro M.; Deakin, Greg; Doddapaneni, Harshavardhan; Floudas, Dimitrios; Grimwood, Jane; Hilden, Kristiina; Kues, Ursula; LaButti, Kurt M.; Lapidus, Alla; Lindquist, Erika A.; Lucas, Susan M.; Murat, Claude; Riley, Robert W.; Salamov, Asaf A.; Schmutz, Jeremy; Subramanian, Venkataramanan; Wosten, Han A. B.; Xu, Jianping; Eastwood, Daniel C.; Foster, Gary D.; Sonnenberg, Anton S. M.; Cullen, Dan; de Vries, Ronald P.; Lundell, Taina; Hibbett, David S.; Henrissat, Bernard; Burton, Kerry S.; Kerrigan, Richard W.; Challen, Michael P.; Grigoriev, Igor V.; Martin, Francis

2012-04-27

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the button mushroom forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics.

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche.

Science.gov (United States)

Morin, Emmanuelle; Kohler, Annegret; Baker, Adam R; Foulongne-Oriol, Marie; Lombard, Vincent; Nagy, Laszlo G; Ohm, Robin A; Patyshakuliyeva, Aleksandrina; Brun, Annick; Aerts, Andrea L; Bailey, Andrew M; Billette, Christophe; Coutinho, Pedro M; Deakin, Greg; Doddapaneni, Harshavardhan; Floudas, Dimitrios; Grimwood, Jane; Hildén, Kristiina; Kües, Ursula; Labutti, Kurt M; Lapidus, Alla; Lindquist, Erika A; Lucas, Susan M; Murat, Claude; Riley, Robert W; Salamov, Asaf A; Schmutz, Jeremy; Subramanian, Venkataramanan; Wösten, Han A B; Xu, Jianping; Eastwood, Daniel C; Foster, Gary D; Sonnenberg, Anton S M; Cullen, Dan; de Vries, Ronald P; Lundell, Taina; Hibbett, David S; Henrissat, Bernard; Burton, Kerry S; Kerrigan, Richard W; Challen, Michael P; Grigoriev, Igor V; Martin, Francis

2012-10-23

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and β-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics.

Revealing the Differences Between Free and Complexed Enzyme Mechanisms and Factors Contributing to Cell Wall Recalcitrance

Energy Technology Data Exchange (ETDEWEB)

Resch, Michael G.; Donohoe, Byron; Ciesielski, Peter; Nill, Jennifer; McKinney, Kellene; Mittal, Ashutosh; Katahira, Rui; Himmel, Michael; Biddy, Mary; Beckham, Gregg; Decker, Steve

2014-09-08

Enzymatic depolymerization of polysaccharides is a key step in the production of fuels and chemicals from lignocellulosic biomass, and discovery of synergistic biomass-degrading enzyme paradigms will enable improved conversion processes. Historically, revealing insights into enzymatic saccharification mechanisms on plant cell walls has been hindered by uncharacterized substrates and low resolution.

Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).

Science.gov (United States)

Narla, S T; Lee, Y-W; Benson, C A; Sarder, P; Brennand, K J; Stachowiak, E K; Stachowiak, M K

2017-07-01

The watershed-hypothesis of schizophrenia asserts that over 200 different mutations dysregulate distinct pathways that converge on an unspecified common mechanism(s) that controls disease ontogeny. Consistent with this hypothesis, our RNA-sequencing of neuron committed cells (NCCs) differentiated from established iPSCs of 4 schizophrenia patients and 4 control subjects uncovered a dysregulated transcriptome of 1349 mRNAs common to all patients. Data reveals a global dysregulation of developmental genome, deconstruction of coordinated mRNA networks, and the formation of aberrant, new coordinated mRNA networks indicating a concerted action of the responsible factor(s). Sequencing of miRNA transcriptomes demonstrated an overexpression of 16 miRNAs and deconstruction of interactive miRNA-mRNA networks in schizophrenia NCCs. ChiPseq revealed that the nuclear (n) form of FGFR1, a pan-ontogenic regulator, is overexpressed in schizophrenia NCCs and overtargets dysregulated mRNA and miRNA genes. The nFGFR1 targeted 54% of all human gene promoters and 84.4% of schizophrenia dysregulated genes. The upregulated genes reside within major developmental pathways that control neurogenesis and neuron formation, whereas downregulated genes are involved in oligodendrogenesis. Our results indicate (i) an early (preneuronal) genomic etiology of schizophrenia, (ii) dysregulated genes and new coordinated gene networks are common to unrelated cases of schizophrenia, (iii) gene dysregulations are accompanied by increased nFGFR1-genome interactions, and (iv) modeling of increased nFGFR1 by an overexpression of a nFGFR1 lead to up or downregulation of selected genes as observed in schizophrenia NCCs. Together our results designate nFGFR1 signaling as a potential common dysregulated mechanism in investigated patients and potential therapeutic target in schizophrenia. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

International Nuclear Information System (INIS)

Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja; Roszak, Aleksander W.; Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel

2015-01-01

The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group

Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

Energy Technology Data Exchange (ETDEWEB)

Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Roszak, Aleksander W. [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel, E-mail: daniel.walker@glasgow.ac.uk [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

2015-06-30

The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.

Bell trajectories for revealing quantum control mechanisms

International Nuclear Information System (INIS)

Dennis, Eric; Rabitz, Herschel

2003-01-01

The dynamics induced while controlling quantum systems by optimally shaped laser pulses have often been difficult to understand in detail. A method is presented for quantifying the importance of specific sequences of quantum transitions involved in the control process. The method is based on a ''beable'' formulation of quantum mechanics due to John Bell that rigorously maps the quantum evolution onto an ensemble of stochastic trajectories over a classical state space. Detailed mechanism identification is illustrated with a model seven-level system. A general procedure is presented to extract mechanism information directly from closed-loop control experiments. Application to simulated experimental data for the model system proves robust with up to 25% noise

The Physical Mechanism of Frictional Aging Revealed by Nanoindentation Creep

Science.gov (United States)

Thom, C.; Carpick, R. W.; Goldsby, D. L.

2017-12-01

A classical observation from rock friction experiments is that friction increases linearly with the logarithm of the time of stationary contact, a phenomenon sometimes referred to as aging. Aging is most often attributed to an increase in the real area of contact due to asperity creep. However, recent atomic force microscopy (AFM) experiments and molecular dynamics simulations suggest that time-dependent siloxane (Si—O—Si) bonding gives rise to aging in silica-silica contacts in the absence of plastic deformation. Determining whether an increase in contact `quantity' (due to creep), contact `quality' (due to chemical bonding), or another unknown mechanism causes aging is a challenging experimental task, despite its importance for developing a physical basis for rate and state friction laws. An intriguing observation is that aging is absent in friction experiments on quartz rocks and gouge at humidities water on asperity creep (via hydrolytic weakening) or on the adhesive strength of contacts. To discern between these possibilities, we have conducted nanoindentation experiments on single crystals of quartz to measure their indentation hardness and creep behavior at humidities of 2% to 50%, and in vacuum. Samples were loaded at 1000 mN/s to a peak load of 15, 40, or 400 mN, which was then held constant for 10 s. After the peak load is reached, the tip sinks into the material with time due to creep of the indentation contact. Our experiments reveal that there is no effect of varying humidity on either indentation hardness or indentation creep behavior over the full range of humidities investigated. If asperity creep were the dominant mechanism of frictional aging for quartz in the experiments cited above, then significant increases in hardness and decreases in the growth rate of indentation contacts at low humidities is expected, in stark contrast with our nanoindentation data. Our experiments indicate that asperity creep cannot be the cause of aging in quartz

Spatiotemporal mechanical variation reveals critical role for rho kinase during primitive streak morphogenesis.

Science.gov (United States)

Henkels, Julia; Oh, Jaeho; Xu, Wenwei; Owen, Drew; Sulchek, Todd; Zamir, Evan

2013-02-01

Large-scale morphogenetic movements during early embryo development are driven by complex changes in biochemical and biophysical factors. Current models for amniote primitive streak morphogenesis and gastrulation take into account numerous genetic pathways but largely ignore the role of mechanical forces. Here, we used atomic force microscopy (AFM) to obtain for the first time precise biomechanical properties of the early avian embryo. Our data reveal that the primitive streak is significantly stiffer than neighboring regions of the epiblast, and that it is stiffer than the pre-primitive streak epiblast. To test our hypothesis that these changes in mechanical properties are due to a localized increase of actomyosin contractility, we inhibited actomyosin contractility via the Rho kinase (ROCK) pathway using the small-molecule inhibitor Y-27632. Our results using several different assays show the following: (1) primitive streak formation was blocked; (2) the time-dependent increase in primitive streak stiffness was abolished; and (3) convergence of epiblast cells to the midline was inhibited. Taken together, our data suggest that actomyosin contractility is necessary for primitive streak morphogenesis, and specifically, ROCK plays a critical role. To better understand the underlying mechanisms of this fundamental process, future models should account for the findings presented in this study.

Attention: Reaction Time and Accuracy Reveal Different Mechanisms

Science.gov (United States)

Prinzmetal, William; McCool, Christin; Park, Samuel

2005-01-01

The authors propose that there are 2 different mechanisms whereby spatial cues capture attention. The voluntary mechanism is the strategic allocation of perceptual resources to the location most likely to contain the target. The involuntary mechanism is a reflexive orienting response that occurs even when the spatial cue does not indicate the…

Cartilaginous Metabolomic Study Reveals Potential Mechanisms of Osteophyte Formation in Osteoarthritis.

Science.gov (United States)

Xu, Zhongwei; Chen, Tingmei; Luo, Jiao; Ding, Shijia; Gao, Sichuan; Zhang, Jian

2017-04-07

Osteophyte is one of the inevitable consequences of progressive osteoarthritis with the main characteristics of cartilage degeneration and endochondral ossification. The pathogenesis of osteophyte formation is not fully understood to date. In this work, metabolomic approaches were employed to explore potential mechanisms of osteophyte formation by detecting metabolic variations between extracts of osteophyte cartilage tissues (n = 32) and uninvolved control cartilage tissues (n = 34), based on the platform of ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, as well as the use of multivariate statistic analysis and univariate statistic analysis. The osteophyte group was significantly separated from the control group by the orthogonal partial least-squares discriminant analysis models, indicating that metabolic state of osteophyte cartilage had been changed. In total, 28 metabolic variations further validated by mass spectrum (MS) match, tandom mass spectrum (MS/MS) match, and standards match mainly included amino acids, sulfonic acids, glycerophospholipids, and fatty acyls. These metabolites were related to some specific physiological or pathological processes (collagen dissolution, boundary layers destroyed, self-restoration triggered, etc.) which might be associated with the procedure of osteophyte formation. Pathway analysis showed phenylalanine metabolism (PI = 0.168, p = 0.004) was highly correlative to this degenerative process. Our findings provided a direction for targeted metabolomic study and an insight into further reveal the molecular mechanisms of ostophyte formation.

Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

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M. Catarina Silva

2016-09-01

Full Text Available Frontotemporal dementia (FTD and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.

QCI Common

Energy Technology Data Exchange (ETDEWEB)

2016-11-18

There are many common software patterns and utilities for the ORNL Quantum Computing Institute that can and should be shared across projects. Otherwise we find duplication of code which adds unwanted complexity. This is a software product seeks to alleviate this by providing common utilities such as object factories, graph data structures, parameter input mechanisms, etc., for other software products within the ORNL Quantum Computing Institute. This work enables pure basic research, has no export controlled utilities, and has no real commercial value.

Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

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Silvia Sookoian

Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

Epitope mapping for monoclonal antibody reveals the activation mechanism for αVβ3 integrin.

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Tetsuji Kamata

Full Text Available Epitopes for a panel of anti-αVβ3 monoclonal antibodies (mAbs were investigated to explore the activation mechanism of αVβ3 integrin. Experiments utilizing αV/αIIb domain-swapping chimeras revealed that among the nine mAbs tested, five recognized the ligand-binding β-propeller domain and four recognized the thigh domain, which is the upper leg of the αV chain. Interestingly, the four mAbs included function-blocking as well as non-functional mAbs, although they bound at a distance from the ligand-binding site. The epitopes for these four mAbs were further determined using human-to-mouse αV chimeras. Among the four, P3G8 recognized an amino acid residue, Ser-528, located on the side of the thigh domain, while AMF-7, M9, and P2W7 all recognized a common epitope, Ser-462, that was located close to the α-genu, where integrin makes a sharp bend in the crystal structure. Fibrinogen binding studies for cells expressing wild-type αVβ3 confirmed that AMF-7, M9, and P2W7 were inhibitory, while P3G8 was non-functional. However, these mAbs were all unable to block binding when αVβ3 was constrained in its extended conformation. These results suggest that AMF-7, M9, and P2W7 block ligand binding allosterically by stabilizing the angle of the bend in the bent conformation. Thus, a switchblade-like movement of the integrin leg is indispensable for the affinity regulation of αVβ3 integrin.

Tumor necrosis factor antagonist mechanisms of action: a comprehensive review

NARCIS (Netherlands)

Tracey, Daniel; Klareskog, Lars; Sasso, Eric H.; Salfeld, Jochen G.; Tak, Paul P.

2008-01-01

During the past 30 years, elucidation of the pathogenesis of rheumatoid arthritis, Crohn's disease, psoriasis, psoriatic arthritis and ankylosing spondylitis at the cellular and molecular levels has revealed that these diseases share common mechanisms and are more closely related than was previously

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche

Science.gov (United States)

Morin, Emmanuelle; Kohler, Annegret; Baker, Adam R.; Foulongne-Oriol, Marie; Lombard, Vincent; Nagye, Laszlo G.; Ohm, Robin A.; Patyshakuliyeva, Aleksandrina; Brun, Annick; Aerts, Andrea L.; Bailey, Andrew M.; Billette, Christophe; Coutinho, Pedro M.; Deakin, Greg; Doddapaneni, Harshavardhan; Floudas, Dimitrios; Grimwood, Jane; Hildén, Kristiina; Kües, Ursula; LaButti, Kurt M.; Lapidus, Alla; Lindquist, Erika A.; Lucas, Susan M.; Murat, Claude; Riley, Robert W.; Salamov, Asaf A.; Schmutz, Jeremy; Subramanian, Venkataramanan; Wösten, Han A. B.; Xu, Jianping; Eastwood, Daniel C.; Foster, Gary D.; Sonnenberg, Anton S. M.; Cullen, Dan; de Vries, Ronald P.; Lundell, Taina; Hibbett, David S.; Henrissat, Bernard; Burton, Kerry S.; Kerrigan, Richard W.; Challen, Michael P.; Grigoriev, Igor V.; Martin, Francis

2012-01-01

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the “button mushroom” forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and β-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics. PMID:23045686

Impairment of leaf photosynthesis after insect herbivory or mechanical injury on common milkweed, Asclepias syriaca.

Science.gov (United States)

Delaney, K J; Haile, F J; Peterson, R K D; Higley, L G

2008-10-01

Insect herbivory has variable consequences on plant physiology, growth, and reproduction. In some plants, herbivory reduces photosynthetic rate (Pn) activity on remaining tissue of injured leaves. We sought to better understand the influence of leaf injury on Pn of common milkweed, Asclepias syriaca (Asclepiadaceae), leaves. Initially, we tested whether Pn reductions occurred after insect herbivory or mechanical injury. We also (1) examined the duration of photosynthetic recovery, (2) compared mechanical injury with insect herbivory, (3) studied the relationship between leaf Pn with leaf injury intensity, and (4) considered uninjured leaf compensatory Pn responses neighboring an injured leaf. Leaf Pn was significantly reduced on mechanically injured or insect-fed leaves in all reported experiments except one, so some factor(s) (cardiac glycoside induction, reproductive investment, and water stress) likely interacts with leaf injury to influence whether Pn impairment occurs. Milkweed tussock moth larval herbivory, Euchaetes egle L. (Arctiidae), impaired leaf Pn more severely than mechanical injury in one experiment. Duration of Pn impairment lasted > 5 d to indicate high leaf Pn sensitivity to injury, but Pn recovery occurred within 13 d in one experiment. The degree of Pn reduction was more severe from E. egle herbivory than similar levels of mechanical tissue removal. Negative linear relationships characterized leaf Pn with percentage tissue loss from single E. egle-fed leaves and mechanically injured leaves and suggested that the signal to trigger leaf Pn impairment on remaining tissue of an injured leaf was amplified by additional tissue loss. Finally, neighboring uninjured leaves to an E. egle-fed leaf had a small (approximately 10%) degree of compensatory Pn to partly offset tissue loss and injured leaf Pn impairment.

Do reflex seizures and spontaneous seizures form a continuum? - triggering factors and possible common mechanisms.

Science.gov (United States)

Irmen, Friederike; Wehner, Tim; Lemieux, Louis

2015-02-01

Recent changes in the understanding and classification of reflex seizures have fuelled a debate on triggering mechanisms of seizures and their conceptual organization. Previous studies and patient reports have listed extrinsic and intrinsic triggers, albeit their multifactorial and dynamic nature is poorly understood. This paper aims to review literature on extrinsic and intrinsic seizure triggers and to discuss common mechanisms among them. Among self-reported seizure triggers, emotional stress is most frequently named. Reflex seizures are typically associated with extrinsic sensory triggers; however, intrinsic cognitive or proprioceptive triggers have also been assessed. The identification of a trigger underlying a seizure may be more difficult if it is intrinsic and complex, and if triggering mechanisms are multifactorial. Therefore, since observability of triggers varies and triggers are also found in non-reflex seizures, the present concept of reflex seizures may be questioned. We suggest the possibility of a conceptual continuum between reflex and spontaneous seizures rather than a dichotomy and discuss evidence to the notion that to some extent most seizures might be triggered. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Revealing −1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods

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Kai-Chun Chang

2012-01-01

Full Text Available Programmed ribosomal frameshifting (PRF serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.

Herbarium specimens reveal a historical shift in phylogeographic structure of common ragweed during native range disturbance.

Science.gov (United States)

Martin, Michael D; Zimmer, Elizabeth A; Olsen, Morten T; Foote, Andrew D; Gilbert, M Thomas P; Brush, Grace S

2014-04-01

Invasive plants provide ample opportunity to study evolutionary shifts that occur after introduction to novel environments. However, although genetic characters pre-dating introduction can be important determinants of later success, large-scale investigations of historical genetic structure have not been feasible. Common ragweed (Ambrosia artemisiifolia L.) is an invasive weed native to North America that is known for its allergenic pollen. Palynological records from sediment cores indicate that this species was uncommon before European colonization of North America, and ragweed populations expanded rapidly as settlers deforested the landscape on a massive scale, later becoming an aggressive invasive with populations established globally. Towards a direct comparison of genetic structure now and during intense anthropogenic disturbance of the late 19th century, we sampled 45 natural populations of common ragweed across its native range as well as historical herbarium specimens collected up to 140 years ago. Bayesian clustering analyses of 453 modern and 473 historical samples genotyped at three chloroplast spacer regions and six nuclear microsatellite loci reveal that historical ragweed's spatial genetic structure mirrors both the palaeo-record of Ambrosia pollen deposition and the historical pattern of agricultural density across the landscape. Furthermore, for unknown reasons, this spatial genetic pattern has changed substantially in the intervening years. Following on previous work relating morphology and genetic expression between plants collected from eastern North America and Western Europe, we speculate that the cluster associated with humans' rapid transformation of the landscape is a likely source of these aggressive invasive populations. © 2014 John Wiley & Sons Ltd.

Informal payments and the quality of health care: Mechanisms revealed by Tanzanian health workers.

Science.gov (United States)

Mæstad, Ottar; Mwisongo, Aziza

2011-02-01

Informal payments for health services are common in many transitional and developing countries. The aim of this paper is to investigate the nature of informal payments in the health sector of Tanzania and to identify mechanisms through which informal payments may affect the quality of health care. Our focus is on the effect of informal payments on health worker behaviours, in particular the interpersonal dynamics among health workers at their workplaces. We organised eight focus groups with 58 health workers representing different cadres and levels of care in one rural and one urban district in Tanzania. We found that health workers at all levels receive informal payments in a number of different contexts. Health workers sometimes share the payments received, but only partially, and more rarely within the cadre than across cadres. Our findings indicate that health workers are involved in 'rent-seeking' activities, such as creating artificial shortages and deliberately lowering the quality of service, in order to extract extra payments from patients or to bargain for a higher share of the payments received by their colleagues. The discussions revealed that many health workers think that the distribution of informal payments is grossly unfair. The findings suggest that informal payments can impact negatively on the quality of health care through rent-seeking behaviours and through frustrations created by the unfair allocation of payments. Interestingly, the presence of corruption may also induce non-corrupt workers to reduce the quality of care. Positive impacts can occur because informal payments may induce health workers to increase their efforts, and maybe more so if there is competition among health workers about receiving the payments. Moreover, informal payments add to health workers' incomes and might thus contribute to retention of health workers within the health sector. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

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Kristina Kirschner

2015-03-01

Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

Immune Mechanisms in Myelodysplastic Syndrome

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Andreas Glenthøj

2016-06-01

Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

What Protein Charging (and Supercharging) Reveal about the Mechanism of Electrospray Ionization

Science.gov (United States)

Ogorzalek Loo, Rachel R.; Lakshmanan, Rajeswari; Loo, Joseph A.

2014-10-01

Understanding the charging mechanism of electrospray ionization is central to overcoming shortcomings such as ion suppression or limited dynamic range, and explaining phenomena such as supercharging. Towards that end, we explore what accumulated observations reveal about the mechanism of electrospray. We introduce the idea of an intermediate region for electrospray ionization (and other ionization methods) to account for the facts that solution charge state distributions (CSDs) do not correlate with those observed by ESI-MS (the latter bear more charge) and that gas phase reactions can reduce, but not increase, the extent of charging. This region incorporates properties (e.g., basicities) intermediate between solution and gas phase. Assuming that droplet species polarize within the high electric field leads to equations describing ion emission resembling those from the equilibrium partitioning model. The equations predict many trends successfully, including CSD shifts to higher m/z for concentrated analytes and shifts to lower m/z for sprays employing smaller emitter opening diameters. From this view, a single mechanism can be formulated to explain how reagents that promote analyte charging ("supercharging") such as m-NBA, sulfolane, and 3-nitrobenzonitrile increase analyte charge from "denaturing" and "native" solvent systems. It is suggested that additives' Brønsted basicities are inversely correlated to their ability to shift CSDs to lower m/z in positive ESI, as are Brønsted acidities for negative ESI. Because supercharging agents reduce an analyte's solution ionization, excess spray charge is bestowed on evaporating ions carrying fewer opposing charges. Brønsted basicity (or acidity) determines how much ESI charge is lost to the agent (unavailable to evaporating analyte).

Fluorescence In Situ Hybridization (FISH-Based Karyotyping Reveals Rapid Evolution of Centromeric and Subtelomeric Repeats in Common Bean (Phaseolus vulgaris and Relatives

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Aiko Iwata-Otsubo

2016-04-01

Full Text Available Fluorescence in situ hybridization (FISH-based karyotyping is a powerful cytogenetics tool to study chromosome organization, behavior, and chromosome evolution. Here, we developed a FISH-based karyotyping system using a probe mixture comprised of centromeric and subtelomeric satellite repeats, 5S rDNA, and chromosome-specific BAC clones in common bean, which enables one to unambiguously distinguish all 11 chromosome pairs. Furthermore, we applied the karyotyping system to several wild relatives and landraces of common bean from two distinct gene pools, as well as other related Phaseolus species, to investigate repeat evolution in the genus Phaseolus. Comparison of karyotype maps within common bean indicates that chromosomal distribution of the centromeric and subtelomeric satellite repeats is stable, whereas the copy number of the repeats was variable, indicating rapid amplification/reduction of the repeats in specific genomic regions. In Phaseolus species that diverged approximately 2–4 million yr ago, copy numbers of centromeric repeats were largely reduced or diverged, and chromosomal distributions have changed, suggesting rapid evolution of centromeric repeats. We also detected variation in the distribution pattern of subtelomeric repeats in Phaseolus species. The FISH-based karyotyping system revealed that satellite repeats are actively and rapidly evolving, forming genomic features unique to individual common bean accessions and Phaseolus species.

GWAS signals across the HLA regions: revealing a clue for common etiology underlying infectious tumors and other immunity diseases

Institute of Scientific and Technical Information of China (English)

Yin Yao Shugart; Ying Wang; Wei-Hua Jia; Yi-Xin Zeng

2011-01-01

Increasing evidence suggests that multiple genes in the human leukocyte antigen (HLA) regions play an important role in development of cancers and immunity disorders. However, the biological mechanisms of the HLA associations are not well understood. We recently conducted a survey of all genome-wide association studies (GWAS) with significant findings in the HLA regions and concluded that diseases such as cancer and immune disorders are more likely to be associated with genetic variants located in the HLA regions than other diseases. This finding is suggestive for testing a hypothesis of a common etiology of infectious tumors and other immunity diseases.

Epitope-dependent mechanisms of CD27 neutralization revealed by X-ray crystallography

Energy Technology Data Exchange (ETDEWEB)

Obmolova, Galina; Teplyakov, Alexey; Malia, Thomas J.; Wunderler, Nicole; Kwok, Deborah; Barone, Linda; Sweet, Raymond; Ort, Tatiana; Scully, Michael; Gilliland, Gary L. (Janssen)

2017-03-01

CD27 is a T and B cell co-stimulatory protein of the TNF receptor superfamily dependent on the availability of the TNF-like ligand CD70. Two anti-CD27 neutralizing monoclonal antibodies were obtained from mouse hybridoma and subsequently humanized and optimized for binding the target. The two antibodies are similar in terms of their CD27-binding affinity and ability to block NF-κB signaling, however their clearance rates in monkeys are very different. The pharmacokinetics profiles could be epitope dependent. To identify the epitopes, we determined the crystal structure of the ternary complex between CD27 and the Fab fragments of these non-competing antibodies. The structure reveals the binding modes of the antibodies suggesting that their mechanisms of action are distinctly different and provides a possible explanation of the in vivo data.

Mechanism of the superior mechanical strength of nanometer-sized metal single crystals revealed

KAUST Repository

Afify, N. D.; Salem, H. G.; Yavari, A.; El Sayed, Tamer S.

2013-01-01

Clear understanding of the superior mechanical strength of nanometer-sized metal single crystals is required to derive advanced mechanical components retaining such superiority. Although high quality studies have been reported on nano

Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid.

Directory of Open Access Journals (Sweden)

Edward D Bonnevie

Full Text Available When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

Trophic cascades triggered by overfishing reveal possible mechanisms of ecosystem regime shifts.

Science.gov (United States)

Daskalov, Georgi M; Grishin, Alexander N; Rodionov, Sergei; Mihneva, Vesselina

2007-06-19

Large-scale transitions between alternative states in ecosystems are known as regime shifts. Once described as healthy and dominated by various marine predators, the Black Sea ecosystem by the late 20th century had experienced anthropogenic impacts such as heavy fishing, cultural eutrophication, and invasions by alien species. We studied changes related to these "natural experiments" to reveal the mechanisms of regime shifts. Two major shifts were detected, the first related to a depletion of marine predators and the second to an outburst of the alien comb jelly Mnemiopsis leidyi; both shifts were triggered by intense fishing resulting in system-wide trophic cascades. The complex nature of ecosystem responses to human activities calls for more elaborate approaches than currently provided by traditional environmental and fisheries management. This implies challenging existing practices and implementing explanatory models of ecosystem interactions that can better reconcile conservation and ecosystem management ideals.

Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

Science.gov (United States)

Ikegami, Keisuke; Yoshimura, Takashi

2016-02-01

Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Understanding the Mechanism behind Maternal Imprisonment and Adolescent School Dropout

Science.gov (United States)

Cho, Rosa M.

2011-01-01

This study empirically tested 3 mechanisms commonly suggested to disadvantage youths whose mothers are incarcerated in prison. An event history analysis of school dropout was conducted on a sample of 6,008 adolescents in a large city created by merging several Illinois state administrative data. Findings revealed that adolescents are indeed at…

The elastic network model reveals a consistent picture on intrinsic functional dynamics of type II restriction endonucleases

International Nuclear Information System (INIS)

Uyar, A; Kurkcuoglu, O; Doruker, P; Nilsson, L

2011-01-01

The vibrational dynamics of various type II restriction endonucleases, in complex with cognate/non-cognate DNA and in the apo form, are investigated with the elastic network model in order to reveal common functional mechanisms in this enzyme family. Scissor-like and tong-like motions observed in the slowest modes of all enzymes and their complexes point to common DNA recognition and cleavage mechanisms. Normal mode analysis further points out that the scissor-like motion has an important role in differentiating between cognate and non-cognate sequences at the recognition site, thus implying its catalytic relevance. Flexible regions observed around the DNA-binding site of the enzyme usually concentrate on the highly conserved β-strands, especially after DNA binding. These β-strands may have a structurally stabilizing role in functional dynamics for target site recognition and cleavage. In addition, hot spot residues based on high-frequency modes reveal possible communication pathways between the two distant cleavage sites in the enzyme family. Some of these hot spots also exist on the shortest path between the catalytic sites and are highly conserved

Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves.

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Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun

2016-03-08

Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves.

Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits

Science.gov (United States)

Marcelletti, Simone; Scortichini, Marco

2015-01-01

The European hazelnut (Corylus avellana) is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches. PMID:26147218

Meta-analysis reveals host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia

KAUST Repository

Cui, Guoxin

2018-02-22

The metabolic symbiosis with photosynthetic algae of the genus Symbiodinium allows corals to thrive in the oligotrophic environments of tropical seas. Many aspects of this relationship have been investigated using transcriptomic analyses in the emerging model organism Aiptasia. However, previous studies identified thousands of putatively symbiosis-related genes, making it difficult to disentangle symbiosis-induced responses from undesired experimental parameters. Using a meta-analysis approach, we identified a core set of 731 high-confidence symbiosis-associated genes that reveal host-dependent recycling of waste ammonium and amino acid synthesis as central processes in this relationship. Combining transcriptomic and metabolomic analyses, we show that symbiont-derived carbon enables host recycling of ammonium into nonessential amino acids. We propose that this provides a regulatory mechanism to control symbiont growth through a carbon-dependent negative feedback of nitrogen availability to the symbiont. The dependence of this mechanism on symbiont-derived carbon highlights the susceptibility of this symbiosis to changes in carbon translocation, as imposed by environmental stress.

Comparative genomic analysis of isoproturon-mineralizing sphingomonads reveals the isoproturon catabolic mechanism.

Science.gov (United States)

Yan, Xin; Gu, Tao; Yi, Zhongquan; Huang, Junwei; Liu, Xiaowei; Zhang, Ji; Xu, Xihui; Xin, Zhihong; Hong, Qing; He, Jian; Spain, Jim C; Li, Shunpeng; Jiang, Jiandong

2016-12-01

The worldwide use of the phenylurea herbicide, isoproturon (IPU), has resulted in considerable concern about its environmental fate. Although many microbial metabolites of IPU are known and IPU-mineralizing bacteria have been isolated, the molecular mechanism of IPU catabolism has not been elucidated yet. In this study, complete genes that encode the conserved IPU catabolic pathway were revealed, based on comparative analysis of the genomes of three IPU-mineralizing sphingomonads and subsequent experimental validation. The complete genes included a novel hydrolase gene ddhA, which is responsible for the cleavage of the urea side chain of the IPU demethylated products; a distinct aniline dioxygenase gene cluster adoQTA1A2BR, which has a broad substrate range; and an inducible catechol meta-cleavage pathway gene cluster adoXEGKLIJC. Furthermore, the initial mono-N-demethylation genes pdmAB were further confirmed to be involved in the successive N-demethylation of the IPU mono-N-demethylated product. These IPU-catabolic genes were organized into four transcription units and distributed on three plasmids. They were flanked by multiple mobile genetic elements and highly conserved among IPU-mineralizing sphingomonads. The elucidation of the molecular mechanism of IPU catabolism will enhance our understanding of the microbial mineralization of IPU and provide insights into the evolutionary scenario of the conserved IPU-catabolic pathway. © 2016 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Electrophysiological potentials reveal cortical mechanisms for mental imagery, mental simulation, and grounded (embodied cognition

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Haline E. Schendan

2012-09-01

Full Text Available Grounded cognition theory proposes that cognition, including meaning, is grounded in sensorimotor processing. The mechanism for grounding cognition is mental simulation, which is a type of mental imagery that re-enacts modal processing. To reveal top-down, cortical mechanisms for mental simulation of shape, event-related potentials were recorded to face and object pictures preceded by mental imagery of a picture. Mental imagery of the identical face or object (congruous condition facilitated not only categorical perception (VPP/N170 but also later visual knowledge (N3[00] complex and linguistic knowledge (N400 for faces more than objects, and strategic semantic analysis (late positive complex between 200 and 700 ms. The later effects resembled semantic congruity effects with pictures. Mental imagery also facilitated category decisions, as a P3(00 peaked earlier for congruous than incongruous (other category pictures, resembling the case when identical pictures repeat immediately. Thus mental imagery mimics semantic congruity and immediate repetition priming processes with pictures. Perception control results showed the opposite for faces and were in the same direction for objects: Perceptual repetition adapts (and so impairs processing of perceived faces from categorical perception onwards, but primes processing of objects during categorical perception, visual knowledge processes, and strategic semantic analysis. For both imagery and perception, differences between faces and objects support domain-specificity and indicate that cognition is grounded in modal processing. Altogether, this direct neural evidence reveals that top-down processes of mental imagery sustain an imagistic representation that mimics perception well enough to prime subsequent perception and cognition. This also suggests that automatic mental simulation of the visual shape of faces and objects operates between 200 and 400 ms, and strategic mental simulation operates between

Mechanism of the superior mechanical strength of nanometer-sized metal single crystals revealed

KAUST Repository

Afify, N. D.

2013-10-01

Clear understanding of the superior mechanical strength of nanometer-sized metal single crystals is required to derive advanced mechanical components retaining such superiority. Although high quality studies have been reported on nano-crystalline metals, the superiority of small single crystals has neither been fundamentally explained nor quantified to this date. Here we present a molecular dynamics study of aluminum single crystals in the size range from 4.1 nm to 40.5 nm. We show that the ultimate mechanical strength deteriorates exponentially as the single crystal size increases. The small crystals superiority is explained by their ability to continuously form vacancies and to recover them. © 2013 Published by Elsevier B.V.

Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis

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Ruffing Anne M

2012-02-01

Full Text Available Abstract Background The ability to synthesize exopolysaccharides (EPS is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

Science.gov (United States)

Fehr, Thorsten; Code, Chris; Herrmann, Manfred

2007-10-03

The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

Science.gov (United States)

Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

2016-01-01

To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

Directory of Open Access Journals (Sweden)

Roussos Charis

2009-12-01

expression profile. Promoter analysis in a representative cluster revealed shared putative cis-elements suggesting a common regulatory transcription mechanism. Conclusions Present results provide novel evidence on the molecular basis of tumor growth inhibition mediated by mastic oil and set a rational basis for application of genomics and bioinformatic methodologies in the screening of natural compounds with potential cancer chemopreventive activities.

Mechanical influences on morphogenesis of the knee joint revealed through morphological, molecular and computational analysis of immobilised embryos.

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Karen A Roddy

2011-02-01

Full Text Available Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.

Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

Science.gov (United States)

Roddy, Karen A.; Prendergast, Patrick J.; Murphy, Paula

2011-01-01

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint. PMID:21386908

Revealing Atomic-Level Mechanisms of Protein Allostery with Molecular Dynamics Simulations.

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Samuel Hertig

2016-06-01

Full Text Available Molecular dynamics (MD simulations have become a powerful and popular method for the study of protein allostery, the widespread phenomenon in which a stimulus at one site on a protein influences the properties of another site on the protein. By capturing the motions of a protein's constituent atoms, simulations can enable the discovery of allosteric binding sites and the determination of the mechanistic basis for allostery. These results can provide a foundation for applications including rational drug design and protein engineering. Here, we provide an introduction to the investigation of protein allostery using molecular dynamics simulation. We emphasize the importance of designing simulations that include appropriate perturbations to the molecular system, such as the addition or removal of ligands or the application of mechanical force. We also demonstrate how the bidirectional nature of allostery-the fact that the two sites involved influence one another in a symmetrical manner-can facilitate such investigations. Through a series of case studies, we illustrate how these concepts have been used to reveal the structural basis for allostery in several proteins and protein complexes of biological and pharmaceutical interest.

The common marmoset monkey: avenues for exploring the prenatal, placental, and postnatal mechanisms in developmental programming of pediatric obesity.

Science.gov (United States)

Riesche, Laren; Tardif, Suzette D; Ross, Corinna N; deMartelly, Victoria A; Ziegler, Toni; Rutherford, Julienne N

2018-05-01

Animal models have been critical in building evidence that the prenatal experience and intrauterine environment are capable of exerting profound and permanent effects on metabolic health through developmental programming of obesity. However, despite physiological and evolutionary similarities, nonhuman primate models are relatively rare. The common marmoset monkey ( Callithrix jacchus) is a New World monkey that has been used as a biomedical model for well more than 50 years and has recently been framed as an appropriate model for exploring early-life impacts on later health and disease. The spontaneous, multifactorial, and early-life development of obesity in the common marmoset make it a valuable research model for advancing our knowledge about the role of the prenatal and placental mechanisms involved in developmental programming of obesity. This paper provides a brief overview of obesity in the common marmoset, followed by a discussion of marmoset reproduction and placental characteristics. We then discuss the occurrence and utility of variable intrauterine environments in developmental programming in marmosets. Evidence of developmental programming of obesity will be given, and finally, we put forward future directions and innovations for including the placenta in developmental programming of obesity in the common marmoset.

Revealing the reaction mechanisms of Li–O2 batteries using environmental transmission electron microscopy

Energy Technology Data Exchange (ETDEWEB)

Luo, Langli; Liu, Bin; Song, Shidong; Xu, Wu; Zhang, Ji-Guang; Wang, Chongmin

2017-03-27

The capacity, Coulombic efficiency, rate, and cyclability of a Li-O2 battery critically depend on the electrode reaction mechanism and the structure/morphology of the reaction product as well as their spatial and temporal evolution1-8, which are all further complicated by the choice of different electrolyte. For the case of aprotic cell, the discharge product, Li2O2, is formed through solution and surface mechanisms9,10, but little is known on the formation mechanism of the perplexing morphology of the reaction product11-15. For the case of Li-O2 battery using solid electrolyte, neither electrode reaction mechanism nor the nature of the reaction production is known. Herein, we reveal the full cycle reaction pathway for Li-O2 batteries and its correlation with the nature of the reaction product. Using an aberration-corrected environmental TEM under oxygen environment, we captured, for the first time, the morphology and phase evolution on the carbon nanotube (CNT) cathode of a working solid-state Li-O2 nano-battery16 and directly correlated these features with electrochemical reaction. We found that the oxygen reduction reaction on CNTs initially produces LiO2, which subsequently evolves to Li2O2 and O2 through disproportionation reaction. Surprisingly it is just the releasing of O2 that inflates the particles to a hollow structure with a Li2O outer surface layer and Li2O2 inner-shell, demonstrating that, in general, accommodation of the released O2 coupled with the Li+ ion diffusion and electron transport paths across both spatial and temporal scales critically governs the morphology of the discharging/charging product in Li-O2 system. We anticipate that the direct observation of Li-O2 reaction mechanisms and their correlation with the morphology of the reaction product set foundation for quantitative understanding/modeling of the electrochemical processes in the Li-O2 system, enabling rational design of both solid-state and aprotic Li-O2 batteries.

Comparative analyses reveal discrepancies among results of commonly used methods for Anopheles gambiaemolecular form identification

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Pinto João

2011-08-01

Full Text Available Abstract Background Anopheles gambiae M and S molecular forms, the major malaria vectors in the Afro-tropical region, are ongoing a process of ecological diversification and adaptive lineage splitting, which is affecting malaria transmission and vector control strategies in West Africa. These two incipient species are defined on the basis of single nucleotide differences in the IGS and ITS regions of multicopy rDNA located on the X-chromosome. A number of PCR and PCR-RFLP approaches based on form-specific SNPs in the IGS region are used for M and S identification. Moreover, a PCR-method to detect the M-specific insertion of a short interspersed transposable element (SINE200 has recently been introduced as an alternative identification approach. However, a large-scale comparative analysis of four widely used PCR or PCR-RFLP genotyping methods for M and S identification was never carried out to evaluate whether they could be used interchangeably, as commonly assumed. Results The genotyping of more than 400 A. gambiae specimens from nine African countries, and the sequencing of the IGS-amplicon of 115 of them, highlighted discrepancies among results obtained by the different approaches due to different kinds of biases, which may result in an overestimation of MS putative hybrids, as follows: i incorrect match of M and S specific primers used in the allele specific-PCR approach; ii presence of polymorphisms in the recognition sequence of restriction enzymes used in the PCR-RFLP approaches; iii incomplete cleavage during the restriction reactions; iv presence of different copy numbers of M and S-specific IGS-arrays in single individuals in areas of secondary contact between the two forms. Conclusions The results reveal that the PCR and PCR-RFLP approaches most commonly utilized to identify A. gambiae M and S forms are not fully interchangeable as usually assumed, and highlight limits of the actual definition of the two molecular forms, which might

Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

KAUST Repository

Mu, Huawei; Sun, Jin; Cheung, Siu Gin; Fang, Ling; Zhou, Haiyun; Luan, Tiangang; Zhang, Huoming; Wong, Chris K.C.; Qiu, Jian-Wen

2017-01-01

Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

Comparative proteomics and codon substitution analysis reveal mechanisms of differential resistance to hypoxia in congeneric snails

KAUST Repository

Mu, Huawei

2017-11-06

Although high-throughput proteomics has been widely applied to study mechanisms of environmental adaptation, the conclusions from studies that are based on one species can be confounded by phylogeny. We compare the freshwater snail Pomacea canaliculata (a notorious invasive species) and its congener Pomacea diffusa (a non-invasive species) to understand the molecular mechanisms of their differential resistance to hypoxia. A 72-h acute exposure experiment showed that P. canaliculata is more tolerant to hypoxia than P. diffusa. The two species were then exposed to three levels of dissolved oxygen (6.7, 2.0 and 1.0mgL−1) for 8h, and their gill proteins were analyzed using iTRAQ-coupled LC-MS/MS. The two species showed striking differences in protein expression profiles, with the more hypoxia tolerant P. canaliculata having more up-regulated proteins in signal transduction and down-regulated proteins in glycolysis and the tricarboxylic acid cycle. Evolutionary analysis revealed five orthologous genes encoding differentially expressed proteins having clear signal of positive selection, indicating selection has acted on some of the hypoxia responsive genes. Our case study has highlighted the potential of integrated proteomics and comparative evolutionary analysis for understanding the genetic basis of adaptation to global environmental change in non-model species. SignificanceRapid globalization in recent decades has greatly facilitated species introduction around the world. Successfully established introduced species, so-called invasive species, have threatened the invaded ecosystems. There has been substantial interest in studying how invasive species respond to extreme environmental conditions because the results can help not only predict their range of expansion and manage their impact, but also may reveal the adaptive mechanisms underlying their invasiveness. Our study has adopted a comparative approach to study the differential physiological and proteomic

Increased BRAF Heterodimerization Is the Common Pathogenic Mechanism for Noonan Syndrome-Associated RAF1 Mutants

Science.gov (United States)

Wu, Xue; Yin, Jiani; Simpson, Jeremy; Kim, Kyoung-Han; Gu, Shengqing; Hong, Jenny H.; Bayliss, Peter; Backx, Peter H.

2012-01-01

Noonan syndrome (NS) is a relatively common autosomal dominant disorder characterized by congenital heart defects, short stature, and facial dysmorphia. NS is caused by germ line mutations in several components of the RAS–RAF–MEK–extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway, including both kinase-activating and kinase-impaired alleles of RAF1 (∼3 to 5%), which encodes a serine-threonine kinase for MEK1/2. To investigate how kinase-impaired RAF1 mutants cause NS, we generated knock-in mice expressing Raf1D486N. Raf1D486N/+ (here D486N/+) female mice exhibited a mild growth defect. Male and female D486N/D486N mice developed concentric cardiac hypertrophy and incompletely penetrant, but severe, growth defects. Remarkably, Mek/Erk activation was enhanced in Raf1D486N-expressing cells compared with controls. RAF1D486N, as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK/ERK activation. Furthermore, kinase-activating RAF1 mutants also required heterodimerization to enhance MEK/ERK activation. Our results suggest that an increased heterodimerization ability is the common pathogenic mechanism for NS-associated RAF1 mutations. PMID:22826437

Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key Msn2 control mechanism.

Science.gov (United States)

Sunnåker, Mikael; Zamora-Sillero, Elias; Dechant, Reinhard; Ludwig, Christina; Busetto, Alberto Giovanni; Wagner, Andreas; Stelling, Joerg

2013-05-28

Predictive dynamical models are critical for the analysis of complex biological systems. However, methods to systematically develop and discriminate among systems biology models are still lacking. We describe a computational method that incorporates all hypothetical mechanisms about the architecture of a biological system into a single model and automatically generates a set of simpler models compatible with observational data. As a proof of principle, we analyzed the dynamic control of the transcription factor Msn2 in Saccharomyces cerevisiae, specifically the short-term mechanisms mediating the cells' recovery after release from starvation stress. Our method determined that 12 of 192 possible models were compatible with available Msn2 localization data. Iterations between model predictions and rationally designed phosphoproteomics and imaging experiments identified a single-circuit topology with a relative probability of 99% among the 192 models. Model analysis revealed that the coupling of dynamic phenomena in Msn2 phosphorylation and transport could lead to efficient stress response signaling by establishing a rate-of-change sensor. Similar principles could apply to mammalian stress response pathways. Systematic construction of dynamic models may yield detailed insight into nonobvious molecular mechanisms.

Philosophy vs the common sense

OpenAIRE

V. V. Chernyshov

2017-01-01

The paper deals with the antinomy of philosophy and the common sense. Philosophy emerges as a way of specifically human knowledge, which purposes analytics of the reality of subjective experience. The study reveals that in order to alienate philosophy from the common sense it was essential to revise the understanding of wisdom. The new, philosophical interpretation of wisdom – offered by Pythagoras – has laid the foundation of any future philosophy. Thus, philosophy emerges, alienating itself...

Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

Science.gov (United States)

Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

2016-08-01

A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

Meta-analysis reveals association between most common class II haplotype in full-heritage Native Americans and rheumatoid arthritis.

Science.gov (United States)

Williams, R C; Jacobsson, L T; Knowler, W C; del Puente, A; Kostyu, D; McAuley, J E; Bennett, P H; Pettitt, D J

1995-01-01

The association of RA with the alleles at the HLA system was tested among Pima and Tohono O'odham Indians (Pimans) of the Gila River Indian Community of Arizona. Serologic class I (HLA-A, -B, and -C) alleles were typed in 51 individuals with RA and in 302 without RA. Serologic class II (HLA-DR, DQ; DR52 DR53) alleles were typed in a subset of 47 with RA and 147 without RA. Molecular subtypes of DR3X6, DRB1*1402, and *1406 were determined in 29 individuals, 16 with RA and 13 without RA. Among the cases with RA, 46 of 47 had the serologic antigen HLA-DR3X6, as did 140 of 147 of those without the disease. However, this association was not statistically significant because of the high prevalence of the antigen in the controls. Data from Pimans were analyzed with similar results from the Tlingit and Yakima Indians. A meta-analysis employing the Mantel-Haenszel procedure, stratified by tribe, revealed a statistically significant association between the most common haplotype, DRB1*1402 DQA1*0501 DQB1*0301 DRB3*0101, and RA (summary odds ratio = 2.63, 95% confidence interval = 1.08, 6.46). There was also a statistically significant difference in the genotype distributions of one class I locus, HLA-C, between those with and without RA (chi 2 = 12.4, 5 df; p = 0.03). It is concluded that the association with the most common class II haplotype in full-heritage Native Americans might help explain their high prevalence of RA.

Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

Energy Technology Data Exchange (ETDEWEB)

Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

2010-06-14

IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

Energy Technology Data Exchange (ETDEWEB)

Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

2010-07-19

IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

Measuring Value in the Commons-Based Ecosystem: Bridging the Gap Between the Commons and the Market

OpenAIRE

De Filippi , Primavera; Hassan , Samer

2014-01-01

International audience; Commons-based peer-production (CBPP) constitutes today an important driver for innovation and cultural development, both online and offline. This led to the establishment of an alternative, Commons-based ecosystem, based on peer-production and collaboration of peers contributing to a common good. Yet, to the extent that this operates outside of the market economy, we cannot rely on traditional market mechanisms (such as pricing) to estimate the value of CBPP. We presen...

Phylogenetic Analysis Reveals Common Antimicrobial Resistant Campylobacter coli Population in Antimicrobial-Free (ABF) and Commercial Swine Systems

Science.gov (United States)

Quintana-Hayashi, Macarena P.; Thakur, Siddhartha

2012-01-01

The objective of this study was to compare the population biology of antimicrobial resistant (AR) Campylobacter coli isolated from swine reared in the conventional and antimicrobial-free (ABF) swine production systems at farm, slaughter and environment. A total of 200 C. coli isolates selected from fecal, environmental, and carcass samples of ABF (n = 100) and conventional (n = 100) swine production systems were typed by multilocus sequence typing (MLST). Sequence data from seven housekeeping genes was analyzed for the identification of allelic profiles, sequence types (STs) and clonal complex determination. Phylogenetic trees were generated to establish the relationships between the genotyped isolates. A total of 51 STs were detected including two novel alleles (glnA 424 and glyA 464) and 14 novel STs reported for the first time. The majority of the C. coli isolates belonged to ST-854 (ABF: 31, conventional: 17), and were grouped in clonal complex ST-828 (ABF: 68%, conventional: 66%). The mean genetic diversity (H) for the ABF (0.3963+/−0.0806) and conventional (0.4655+/−0.0714) systems were similar. The index of association () for the ABF ( = 0.1513) and conventional ( = 0.0991) C. coli populations were close to linkage equilibrium, indicative of a freely recombining population. Identical STs were detected between the pigs and their environment both at farm and slaughter. A minimum spanning tree revealed the close clustering of C. coli STs that originated from swine and carcass with those from the environment. In conclusion, our study reveals a genotypic diverse C. coli population that shares a common ancestry in the conventional and ABF swine production systems. This could potentially explain the high prevalence of antimicrobial resistant C. coli in the ABF system in the absence of antimicrobial selection pressure. PMID:22984540

The Cost Effectiveness of the U.S. Export Enhancement Program Bonus Allocation Mechanism

OpenAIRE

Humei Wang; Richard J. Sexton

2004-01-01

The U.S. Export Enhancement Program is evaluated from the perspective of the cost effectiveness of its bonus allocation mechanism. The current mechanism resembles a discriminatory-price, common-value auction. However, auction theory suggests that a discriminatory auction may not be optimal in this setting for several reasons. This article evaluates the current format relative to an alternative, uniform-price auction. Estimation results reveal evidence of strategic bidder behavior under the cu...

Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

DEFF Research Database (Denmark)

Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana

2008-01-01

Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p...... penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML.......42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete...

A dominant-negative mutant inhibits multiple prion variants through a common mechanism.

Directory of Open Access Journals (Sweden)

Fen Pei

2017-10-01

Full Text Available Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.

Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.

Science.gov (United States)

Sikirzhytski, Vitali; Topilina, Natalya I; Takor, Gaius A; Higashiya, Seiichiro; Welch, John T; Uversky, Vladimir N; Lednev, Igor K

2012-05-14

Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.

Common Arterial Trunk in a 3-Day-Old Alpaca Cria

Directory of Open Access Journals (Sweden)

Tsumugi Anne Kurosawa

2016-01-01

Full Text Available A 3-day-old alpaca cria presented for progressive weakness and dyspnea since birth. Complete bloodwork, thoracic radiographs, and endoscopic examination of the nasal passages and distal trachea revealed no significant findings. Echocardiogram and contrast study revealed a single artery overriding a large ventricular septal defect (VSD. A small atrial septal defect or patent foramen ovale was also noted. Color flow Doppler and an agitated saline contrast study revealed bidirectional but primarily right to left flow through the VSD and bidirectional shunting through the atrial defect. Differential diagnosis based on echocardiographic findings included common arterial trunk, Tetralogy of Fallot, and pulmonary atresia with a VSD. Postmortem examination revealed a large common arterial trunk with a quadricuspid valve overriding a VSD. Additionally, defect in the atrial septum was determined to be a patent foramen ovale. A single pulmonary trunk arose from the common arterial trunk and bifurcated to the left and right pulmonary artery, consistent with a Collet and Edwards’ type I common arterial trunk with aortic predominance. Although uncommon, congenital cardiac defects should be considered in animals presenting with clinical signs of hypoxemia, dyspnea, or failure to thrive.

Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs).

Science.gov (United States)

Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

2013-01-01

Polyhydroxyalkanoates (PHAs) have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

NARCIS (Netherlands)

Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; Maloney, Cliona M.; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P. R.; Mehta, Amar; van Iperen, Erik P. A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M. A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; de Boer, Anthonius; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E. K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; Meyer, Nuala J.; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszewski, Maciej; Tomaszweski, Maciej; Verschuren, W. M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I. W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; Christie, Jason D.; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F. A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

2011-01-01

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

Directory of Open Access Journals (Sweden)

Claudio Franceschi

2018-03-01

Full Text Available Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs and geriatric syndromes (GSs, is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are

Tracking planets and moons: mechanisms of object tracking revealed with a new paradigm.

Science.gov (United States)

Tombu, Michael; Seiffert, Adriane E

2011-04-01

People can attend to and track multiple moving objects over time. Cognitive theories of this ability emphasize location information and differ on the importance of motion information. Results from several experiments have shown that increasing object speed impairs performance, although speed was confounded with other properties such as proximity of objects to one another. Here, we introduce a new paradigm to study multiple object tracking in which object speed and object proximity were manipulated independently. Like the motion of a planet and moon, each target-distractor pair rotated about both a common local point as well as the center of the screen. Tracking performance was strongly affected by object speed even when proximity was controlled. Additional results suggest that two different mechanisms are used in object tracking--one sensitive to speed and proximity and the other sensitive to the number of distractors. These observations support models of object tracking that include information about object motion and reject models that use location alone.

Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions

Science.gov (United States)

Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G.; Módos, Károly; Kardos, József; Liliom, Károly

2010-01-01

Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin–sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well.—Kovacs, E., Harmat, V., Tóth, J., Vértessy, B. G., Módos, K., Kardos, J., Liliom, K. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions. PMID:20522785

"Gear mechanism" of bariatric interventions revealed by untargeted metabolomics.

Science.gov (United States)

Samczuk, Paulina; Luba, Magdalena; Godzien, Joanna; Mastrangelo, Annalaura; Hady, Hady Razak; Dadan, Jacek; Barbas, Coral; Gorska, Maria; Kretowski, Adam; Ciborowski, Michal

2018-03-20

Mechanisms responsible for metabolic gains after bariatric surgery are not entirely clear. The purpose of this study was evaluation of metabolic changes after laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy in semi-annual follow up. The study participants were selected from obese patients with T2DM who underwent one of the mentioned bariatric procedures. Serum metabolic fingerprinting by use of liquid and gas chromatography with mass spectrometry detection was performed on samples obtained from studied patients before, one, and six months post-surgery. Performed analyses resulted in 49 significant and identified metabolites. Comparison of the two described procedures has allowed to detect metabolites linked with numerous pathways, processes and diseases. Based on the metabolites detected and pathways affected, we propose a "gear mechanism" showing molecular changes evoked by both bariatric procedures. Critical evaluation of clinical data and obtained metabolomics results enables us to conclude that both procedures are very similar in terms of general clinical outcome, but they strongly differ from each other in molecular mechanisms leading to the final effect. For the first time general metabolic effect of bariatric procedures is described. New hypotheses concerning molecular mechanisms induced by bariatric surgeries and new gut microbiota modulations are presented. Copyright © 2018 Elsevier B.V. All rights reserved.

The mechanics of anaphase B in a basidiomycete as revealed by laser microbeam microsurgery

International Nuclear Information System (INIS)

Bayles, C.J.; Aist, J.R.; Berns, M.W.

1993-01-01

Bayles, C. J., Aist, J. R., and Berns, M. W. 1993. The mechanics of anaphase B in a basidiomycete as revealed by laser microbeam microsurgery. Experimental Mycology 17, 191-199. Cytoplasmic forces were found to be actively pulling on the spindle pole bodies during anaphase B in the dikaryotic, basidiomycete fungus, Helicobasidium mompa. When the spindle of one nucleus was severed with a laser microbeam at mid anaphase B, its two spindle pole bodies separated at a much faster rate than did those of the intact spindle in the other nucleus of the same cell. Since astral microtubule populations apparently reach their maximum during anaphase B in this fungus, we suggest that these microtubules may be involved in the cytoplasmic pulling forces. The spindle appears to act primarily as a governor, regulating the rate at which the spindle pole bodies are separated

Structure of a prokaryotic sodium channel pore reveals essential gating elements and an outer ion binding site common to eukaryotic channels.

Science.gov (United States)

Shaya, David; Findeisen, Felix; Abderemane-Ali, Fayal; Arrigoni, Cristina; Wong, Stephanie; Nurva, Shailika Reddy; Loussouarn, Gildas; Minor, Daniel L

2014-01-23

Voltage-gated sodium channels (NaVs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial NaV (BacNaV) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of NaVAe1p, a pore-only BacNaV derived from NaVAe1, a BacNaV from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNaVs show that two elements defined by the NaVAe1p structure, an S6 activation gate position and the cytoplasmic tail "neck", are central to BacNaV gating. The structure also reveals the selectivity filter ion entry site, termed the "outer ion" site. Comparison with mammalian voltage-gated calcium channel (CaV) selectivity filters, together with functional studies, shows that this site forms a previously unknown determinant of CaV high-affinity calcium binding. Our findings underscore commonalities between BacNaVs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily. © 2013. Published by Elsevier Ltd. All rights reserved.

Mechanism of crack healing at room temperature revealed by atomistic simulations

International Nuclear Information System (INIS)

Li, J.; Fang, Q.H.; Liu, B.; Liu, Y.; Liu, Y.W.; Wen, P.H.

2015-01-01

Three dimensional molecular dynamics (MD) simulations are systematically carried out to reveal the mechanism of the crack healing at room temperature, in terms of the dislocation shielding and the atomic diffusion to control the crack closure, in a copper (Cu) plate suffering from a shear loading. The results show that the process of the crack healing is actualized through the dislocation emission at a crack tip accompanied with intrinsic stacking faults ribbon forming in the crack tip wake, the dislocation slipping in the matrix and the dislocation annihilation in the free surface. Dislocation included stress compressing the crack tip is examined from the MD simulations and the analytical models, and then the crack closes rapidly due to the assistance of the atomic diffusion induced by the thermal activation when the crack opening displacement is less than a threshold value. This phenomenon is very different from the previous results for the crack propagation under the external load applied because of the crack healing (advancing) largely dependent on the crystallographic orientations of crack and the directions of external loading. Furthermore, based on the energy characteristic and considering the crack size effect, a theoretical model is established to predict the relationships between the crack size and the shear stress which qualitatively agree well with that obtained in the MD simulations

Are common names becoming less common? The rise in uniqueness and individualism in Japan.

Science.gov (United States)

Ogihara, Yuji; Fujita, Hiroyo; Tominaga, Hitoshi; Ishigaki, Sho; Kashimoto, Takuya; Takahashi, Ayano; Toyohara, Kyoko; Uchida, Yukiko

2015-01-01

We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual's psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common

Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

Directory of Open Access Journals (Sweden)

Huizheng Wang

Full Text Available Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

Proteomic analysis reveals resistance mechanism against biofuel hexane in Synechocystis sp. PCC 6803

Directory of Open Access Journals (Sweden)

Liu Jie

2012-09-01

Full Text Available Abstract Background Recent studies have demonstrated that photosynthetic cyanobacteria could be an excellent cell factory to produce renewable biofuels and chemicals due to their capability to utilize solar energy and CO2 as the sole energy and carbon sources. Biosynthesis of carbon-neutral biofuel alkanes with good chemical and physical properties has been proposed. However, to make the process economically feasible, one major hurdle to improve the low cell tolerance to alkanes needed to be overcome. Results Towards the goal to develop robust and high-alkane-tolerant hosts, in this study, the responses of model cyanobacterial Synechocystis PCC 6803 to hexane, a representative of alkane, were investigated using a quantitative proteomics approach with iTRAQ - LC-MS/MS technologies. In total, 1,492 unique proteins were identified, representing about 42% of all predicted protein in the Synechocystis genome. Among all proteins identified, a total of 164 and 77 proteins were found up- and down-regulated, respectively. Functional annotation and KEGG pathway enrichment analyses showed that common stress responses were induced by hexane in Synechocystis. Notably, a large number of transporters and membrane-bound proteins, proteins against oxidative stress and proteins related to sulfur relay system and photosynthesis were induced, suggesting that they are possibly the major protection mechanisms against hexane toxicity. Conclusion The study provided the first comprehensive view of the complicated molecular mechanism employed by cyanobacterial model species, Synechocystis to defend against hexane stress. The study also provided a list of potential targets to engineer Synechocystis against hexane stress.

Is there a Common Genetic Basis for Autoimmune Diseases?

Directory of Open Access Journals (Sweden)

Juan-Manuel Anaya

2006-01-01

Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

Micro-mechanics of ionic electroactive polymer actuators

Science.gov (United States)

Punning, Andres; Põldsalu, Inga; Kaasik, Friedrich; Vunder, Veiko; Aabloo, Alvo

2015-04-01

Commonly, modeling of the bending behavior of the ionic electroactive polymer (IEAP) actuators is based on the classical mechanics of cantilever beam. It is acknowledged, that the actuation of the ionic electroactive polymer (IEAP) actuators is symmetric about the centroid - the convex side of the actuator is expanding and the concave side is contracting for exactly the same amount, while the thickness of the actuator remains invariant. Actuating the IEAP actuators and sensors under scanning electron microscope (SEM), in situ, reveals that for some types of them this approach is incorrect. Comparison of the SEM micrographs using the Digital Image Correction (DIC) method results with the precise strain distribution of the IEAP actuators in two directions: in the axial direction, and in the direction of thickness. This information, in turn, points to the physical processes taking place within the electrodes as well as membrane of the trilayer laminate of sub-millimeter thickness. Comparison of the EAP materials, engaged as an actuator as well as a sensor, reveals considerable differences between the micro-mechanics of the two modes.

Atomic force microscopy stiffness tomography on living Arabidopsis thaliana cells reveals the mechanical properties of surface and deep cell-wall layers during growth.

Science.gov (United States)

Radotić, Ksenija; Roduit, Charles; Simonović, Jasna; Hornitschek, Patricia; Fankhauser, Christian; Mutavdžić, Dragosav; Steinbach, Gabor; Dietler, Giovanni; Kasas, Sandor

2012-08-08

Cell-wall mechanical properties play a key role in the growth and the protection of plants. However, little is known about genuine wall mechanical properties and their growth-related dynamics at subcellular resolution and in living cells. Here, we used atomic force microscopy (AFM) stiffness tomography to explore stiffness distribution in the cell wall of suspension-cultured Arabidopsis thaliana as a model of primary, growing cell wall. For the first time that we know of, this new imaging technique was performed on living single cells of a higher plant, permitting monitoring of the stiffness distribution in cell-wall layers as a function of the depth and its evolution during the different growth phases. The mechanical measurements were correlated with changes in the composition of the cell wall, which were revealed by Fourier-transform infrared (FTIR) spectroscopy. In the beginning and end of cell growth, the average stiffness of the cell wall was low and the wall was mechanically homogenous, whereas in the exponential growth phase, the average wall stiffness increased, with increasing heterogeneity. In this phase, the difference between the superficial and deep wall stiffness was highest. FTIR spectra revealed a relative increase in the polysaccharide/lignin content. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Phenotyping common beans for adaptation to drought

Science.gov (United States)

Beebe, Stephen E.; Rao, Idupulapati M.; Blair, Matthew W.; Acosta-Gallegos, Jorge A.

2013-01-01

Common beans (Phaseolus vulgaris L.) originated in the New World and are the grain legume of greatest production for direct human consumption. Common bean production is subject to frequent droughts in highland Mexico, in the Pacific coast of Central America, in northeast Brazil, and in eastern and southern Africa from Ethiopia to South Africa. This article reviews efforts to improve common bean for drought tolerance, referring to genetic diversity for drought response, the physiology of drought tolerance mechanisms, and breeding strategies. Different races of common bean respond differently to drought, with race Durango of highland Mexico being a major source of genes. Sister species of P. vulgaris likewise have unique traits, especially P. acutifolius which is well adapted to dryland conditions. Diverse sources of tolerance may have different mechanisms of plant response, implying the need for different methods of phenotyping to recognize the relevant traits. Practical considerations of field management are discussed including: trial planning; water management; and field preparation. PMID:23507928

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van IJcken, W.; Bartke, A.; Spindler, S.R.; Hoeijmakers, J.H.J.; van der Horst, G.T.J.; Garinis, G.A.

2008-01-01

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the

Delayed and accelerated aging share common longevity assurance mechanisms

NARCIS (Netherlands)

B. Schumacher (Björn); I. van der Pluijm (Ingrid); M.J. Moorhouse (Michael); T. Kosteas (Theodore); A.R. Robinson (Andria Rasile); Y. Suh (Yousin); T.M. Breit (Timo); H. van Steeg (Harry); L.J. Niedernhofer (Laura); W.F.J. van IJcken (Wilfred); A. Bartke (Andrzej); S.R. Spindler (Stephen); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); G.A. Garinis (George)

2008-01-01

textabstractMutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between

Azadirachtin(A) distinctively modulates subdomain 2 of actin - novel mechanism to induce depolymerization revealed by molecular dynamics study.

Science.gov (United States)

Pravin Kumar, R; Roopa, L; Sudheer Mohammed, M M; Kulkarni, Naveen

2016-12-01

Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. The mechanism by which AZA induces actin depolymerization is not clearly understood. Therefore, different computational experiments were conducted to delineate the precise mechanism of AZA-induced actin depolymerization. Molecular dynamics studies showed that AZA strongly interacted with subdomain 2 and destabilized the interactions between subdomain 2 of one actin and subdomains 1 and 4 of the adjacent actin, causing the separation of actin subunits. The separation was observed between subdomain 3 of subunit n and subdomain 4 of subunit n + 2. However, the specific triggering point for the separation of the subunits was the destabilization of direct interactions between subdomain 2 of subunit n (Arg39, Val45, Gly46 and Arg62) and subdomain 4 of subunit n + 2 (Asp286, Ile287, Asp288, Ile289, Asp244 and Lys291). These results reveal a unique mechanism of an actin filament modulator that induces depolymerization. This mechanism of AZA can be used to design similar molecules against mammalian actins for cancer therapy.

A combined cryo-EM and molecular dynamics approach reveals the mechanism of ErmBL-mediated translation arrest

Science.gov (United States)

Arenz, Stefan; Bock, Lars V.; Graf, Michael; Innis, C. Axel; Beckmann, Roland; Grubmüller, Helmut; Vaiana, Andrea C.; Wilson, Daniel N.

2016-07-01

Nascent polypeptides can induce ribosome stalling, regulating downstream genes. Stalling of ErmBL peptide translation in the presence of the macrolide antibiotic erythromycin leads to resistance in Streptococcus sanguis. To reveal this stalling mechanism we obtained 3.6-Å-resolution cryo-EM structures of ErmBL-stalled ribosomes with erythromycin. The nascent peptide adopts an unusual conformation with the C-terminal Asp10 side chain in a previously unseen rotated position. Together with molecular dynamics simulations, the structures indicate that peptide-bond formation is inhibited by displacement of the peptidyl-tRNA A76 ribose from its canonical position, and by non-productive interactions of the A-tRNA Lys11 side chain with the A-site crevice. These two effects combine to perturb peptide-bond formation by increasing the distance between the attacking Lys11 amine and the Asp10 carbonyl carbon. The interplay between drug, peptide and ribosome uncovered here also provides insight into the fundamental mechanism of peptide-bond formation.

Recombination rate plasticity: revealing mechanisms by design

Science.gov (United States)

Sefick, Stephen; Rushton, Chase

2017-01-01

For over a century, scientists have known that meiotic recombination rates can vary considerably among individuals, and that environmental conditions can modify recombination rates relative to the background. A variety of external and intrinsic factors such as temperature, age, sex and starvation can elicit ‘plastic’ responses in recombination rate. The influence of recombination rate plasticity on genetic diversity of the next generation has interesting and important implications for how populations evolve. Further, many questions remain regarding the mechanisms and molecular processes that contribute to recombination rate plasticity. Here, we review 100 years of experimental work on recombination rate plasticity conducted in Drosophila melanogaster. We categorize this work into four major classes of experimental designs, which we describe via classic studies in D. melanogaster. Based on these studies, we highlight molecular mechanisms that are supported by experimental results and relate these findings to studies in other systems. We synthesize lessons learned from this model system into experimental guidelines for using recent advances in genotyping technologies, to study recombination rate plasticity in non-model organisms. Specifically, we recommend (1) using fine-scale genome-wide markers, (2) collecting time-course data, (3) including crossover distribution measurements, and (4) using mixed effects models to analyse results. To illustrate this approach, we present an application adhering to these guidelines from empirical work we conducted in Drosophila pseudoobscura. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109222

Electrochemistry and capillary condensation theory reveal the mechanism of corrosion in dense porous media.

Science.gov (United States)

Stefanoni, Matteo; Angst, Ueli M; Elsener, Bernhard

2018-05-09

Corrosion in carbonated concrete is an example of corrosion in dense porous media of tremendous socio-economic and scientific relevance. The widespread research endeavors to develop novel, environmentally friendly cements raise questions regarding their ability to protect the embedded steel from corrosion. Here, we propose a fundamentally new approach to explain the scientific mechanism of corrosion kinetics in dense porous media. The main strength of our model lies in its simplicity and in combining the capillary condensation theory with electrochemistry. This reveals that capillary condensation in the pore structure defines the electrochemically active steel surface, whose variability upon changes in exposure relative humidity is accountable for the wide variability in measured corrosion rates. We performed experiments that quantify this effect and find good agreement with the theory. Our findings are essential to devise predictive models for the corrosion performance, needed to guarantee the safety and sustainability of traditional and future cements.

Flavonoids and Melanins: a common strategy across two kingdoms.

Science.gov (United States)

Carletti, Giorgia; Nervo, Giuseppe; Cattivelli, Luigi

2014-01-01

Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.

The Mechanisms of Aberrant Protein Aggregation

Science.gov (United States)

Cohen, Samuel; Vendruscolo, Michele; Dobson, Chris; Knowles, Tuomas

2012-02-01

We discuss the development of a kinetic theory for understanding the aberrant loss of solubility of proteins. The failure to maintain protein solubility results often in the assembly of organized linear structures, commonly known as amyloid fibrils, the formation of which is associated with over 50 clinical disorders including Alzheimer's and Parkinson's diseases. A true microscopic understanding of the mechanisms that drive these aggregation processes has proved difficult to achieve. To address this challenge, we apply the methodologies of chemical kinetics to the biomolecular self-assembly pathways related to protein aggregation. We discuss the relevant master equation and analytical approaches to studying it. In particular, we derive the underlying rate laws in closed-form using a self-consistent solution scheme; the solutions that we obtain reveal scaling behaviors that are very generally present in systems of growing linear aggregates, and, moreover, provide a general route through which to relate experimental measurements to mechanistic information. We conclude by outlining a study of the aggregation of the Alzheimer's amyloid-beta peptide. The study identifies the dominant microscopic mechanism of aggregation and reveals previously unidentified therapeutic strategies.

Component Commonality and Its Cost Implications - Increasing the Commonality of the Right Components

DEFF Research Database (Denmark)

Lyly-Yrjänäinen, Jouni; Suomala, Petri; Israelsen, Poul

Component commonality (Labro 2004, Zhou & Gruppström 2004) can be defined as the use of the same version of a component across multiple products. It is usually seen as a means to manage costs without sacrificing product variety. However, when managing costs with component commonality, the managers...... constructions was identified as the most important bottleneck for the delivery process causing many indirect costs, especially with respect to project-management-related activities. Interestingly, by eliminating the need for mechanical engineering, the context starts to approach assembly-to-order context, also...... should be able to identify rather rapidly which group of components would enable the most significant cost reductions. Unfortunately, the existing literature lacks profound discussion of how to identify the right components for increased component commonality. The objective of the paper is to discuss how...

Spores of most common airborne fungi reveal no ice nucleation activity

Science.gov (United States)

Pummer, B. G.; Atanasova, L.; Bauer, H.; Bernardi, J.; Druzhinina, I. S.; Grothe, H.

2013-06-01

Fungal spores are ubiquitous biological aerosols, which are considered to show ice nucleation (IN) activity. In this study the respective IN activity was tested in oil emulsion in the immersion freezing mode. The focus was laid on species of economical, ecological or sanitary significance. For the first time, not only common moulds, but also edible mushrooms (Basidiomycota, Agaricomycetes) were investigated, as they contribute massively to the total amount of fungal spores in the atmosphere. Only Fusarium avenaceum showed freezing events at low subzero-temperatures, while the other investigated fungal spores showed no significant IN activity. Furthermore, we selected a set of fungal strains from different sites and exposed them to occasional freezing stress during cultivation. Although the total protein expression was altered by this treatment, it had no significant impact on the IN activity.

Efficient prion disease transmission through common environmental materials.

Science.gov (United States)

Pritzkow, Sandra; Morales, Rodrigo; Lyon, Adam; Concha-Marambio, Luis; Urayama, Akihiko; Soto, Claudio

2018-03-02

Prion diseases are a group of fatal neurodegenerative diseases associated with a protein-based infectious agent, termed prion. Compelling evidence suggests that natural transmission of prion diseases is mediated by environmental contamination with infectious prions. We hypothesized that several natural and man-made materials, commonly found in the environments of wild and captive animals, can bind prions and may act as vectors for disease transmission. To test our hypothesis, we exposed surfaces composed of various common environmental materials ( i.e. wood, rocks, plastic, glass, cement, stainless steel, aluminum, and brass) to hamster-adapted 263K scrapie prions and studied their attachment and retention of infectivity in vitro and in vivo Our results indicated that these surfaces, with the sole exception of brass, efficiently bind, retain, and release prions. Prion replication was studied in vitro using the protein misfolding cyclic amplification technology, and infectivity of surface-bound prions was analyzed by intracerebrally challenging hamsters with contaminated implants. Our results revealed that virtually all prion-contaminated materials transmitted the disease at high rates. To investigate a more natural form of exposure to environmental contamination, we simply housed animals with large contaminated spheres made of the different materials under study. Strikingly, most of the hamsters developed classical clinical signs of prion disease and typical disease-associated brain changes. Our findings suggest that prion contamination of surfaces commonly present in the environment can be a source of disease transmission, thus expanding our understanding of the mechanisms for prion spreading in nature. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Patterned biofilm formation reveals a mechanism for structural heterogeneity in bacterial biofilms.

Science.gov (United States)

Gu, Huan; Hou, Shuyu; Yongyat, Chanokpon; De Tore, Suzanne; Ren, Dacheng

2013-09-03

Bacterial biofilms are ubiquitous and are the major cause of chronic infections in humans and persistent biofouling in industry. Despite the significance of bacterial biofilms, the mechanism of biofilm formation and associated drug tolerance is still not fully understood. A major challenge in biofilm research is the intrinsic heterogeneity in the biofilm structure, which leads to temporal and spatial variation in cell density and gene expression. To understand and control such structural heterogeneity, surfaces with patterned functional alkanthiols were used in this study to obtain Escherichia coli cell clusters with systematically varied cluster size and distance between clusters. The results from quantitative imaging analysis revealed an interesting phenomenon in which multicellular connections can be formed between cell clusters depending on the size of interacting clusters and the distance between them. In addition, significant differences in patterned biofilm formation were observed between wild-type E. coli RP437 and some of its isogenic mutants, indicating that certain cellular and genetic factors are involved in interactions among cell clusters. In particular, autoinducer-2-mediated quorum sensing was found to be important. Collectively, these results provide missing information that links cell-to-cell signaling and interaction among cell clusters to the structural organization of bacterial biofilms.

Talaromyces marneffei Genomic, Transcriptomic, Proteomic and Metabolomic Studies Reveal Mechanisms for Environmental Adaptations and Virulence

Directory of Open Access Journals (Sweden)

Susanna K. P. Lau

2017-06-01

Full Text Available Talaromyces marneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus. Among the 14 Mp1p homologs, only Mp1p is a virulence factor binding a variety of host proteins, fatty acids and lipids. There are 23 polyketide synthase genes, one for melanin and two for mitorubrinic acid/mitorubrinol biosynthesis, which are virulence factors. Another polyketide synthase is for biogenesis of the diffusible red pigment, which consists of amino acid conjugates of monascorubin and rubropunctatin. Novel microRNA-like RNAs (milRNAs and processing proteins are present. The dicer protein, dcl-2, is required for biogenesis of two milRNAs, PM-milR-M1 and PM-milR-M2, which are more highly expressed in hyphal cells. Comparative transcriptomics showed that tandem repeat-containing genes were overexpressed in yeast phase, generating protein polymorphism among cells, evading host’s immunity. Comparative proteomics between yeast and hyphal cells revealed that glyceraldehyde-3-phosphate dehydrogenase, up-regulated in hyphal cells, is an adhesion factor for conidial attachment.

Quantum mechanics, common sense and the black hole information paradox

CERN Document Server

Danielsson, U H; Danielsson, Ulf H.; Schiffer, Marcelo

1993-01-01

The purpose of this paper is to analyse, in the light of information theory and with the arsenal of (elementary) quantum mechanics (EPR correlations, copying machines, teleportation, mixing produced in sub-systems owing to a trace operation, etc.) the scenarios available on the market to resolve the so-called black-hole information paradox. We shall conclude that the only plausible ones are those where either the unitary evolution of quantum mechanics is given up, in which information leaks continuously in the course of black-hole evaporation through non-local processes, or those in which the world is polluted by an infinite number of meta-stable remnants.

Systematic analysis of phloem-feeding insect-induced transcriptional reprogramming in Arabidopsis highlights common features and reveals distinct responses to specialist and generalist insects.

Science.gov (United States)

Foyer, Christine H; Verrall, Susan R; Hancock, Robert D

2015-02-01

Phloem-feeding insects (PFIs), of which aphids are the largest group, are major agricultural pests causing extensive damage to crop plants. In contrast to chewing insects, the nature of the plant response to PFIs remains poorly characterized. Scrutiny of the literature concerning transcriptional responses of model and crop plant species to PFIs reveals surprisingly little consensus with respect to the transcripts showing altered abundance following infestation. Nevertheless, core features of the transcriptional response to PFIs can be defined in Arabidopsis thaliana. This comparison of the PFI-associated transcriptional response observed in A. thaliana infested by the generalists Myzus persicae and Bemisia tabaci with the specialist Brevicoryne brassicae highlights the importance of calcium-dependent and receptor kinase-associated signalling. We discuss these findings within the context of the complex cross-talk between the different hormones regulating basal immune response mechanisms in plants. We identify PFI-responsive genes, highlighting the importance of cell wall-associated kinases in plant-PFI interactions, as well as the significant role of kinases containing the domain of unknown function 26. A common feature of plant-PFI interaction is enhanced abundance of transcripts encoding WRKY transcription factors. However, significant divergence was observed with respect to secondary metabolism dependent upon the insect attacker. Transcripts encoding enzymes and proteins associated with glucosinolate metabolism were decreased following attack by the generalist M. persicae but not by the specialist B. brassicae. This analysis provides a comprehensive overview of the molecular patterns associated with the plant response to PFIs and suggests that plants recognize and respond to perturbations in the cell wall occurring during PFI infestation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights

Commoning in the periphery – The role of the commons for understanding rural continuities and change

Directory of Open Access Journals (Sweden)

Emil Sandström

2017-03-01

Full Text Available This paper explores how commons reproduce over time and introduces the concept of commoning to discuss rural continuities and change. The point of departure is that commons are essential for local community development in that they have an important role for mediating social change and for local identity production. Through an ethnographic and historical study of a number of commons systems from the village of Ängersjö in the Midwest of Sweden, the paper argues for a more historically and socially grounded understanding of how commons evolve. The paper examines Ängersjö’s commons within two broad historical time frames – the pre-industrial (4th to 20th century and the post-industrial time periods (20th century to the present – in order to understand commons, not just as arenas for resource extraction and resource struggles, but also as important contexts for identity formation, local mobilisation and for shaping rural change. The paper reveals how the commons have co-evolved with changes in society at large and how the meanings and functions of the commons have changed throughout history – from being important economic resources – to cultural and symbolic resources that have created new avenues for collective action.

Are common names becoming less common? The rise in uniqueness and individualism in Japan

Directory of Open Access Journals (Sweden)

Yuji eOgihara

2015-10-01

Full Text Available We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual’s psyche and behavior outside the head; e.g., advertising can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by

Are common names becoming less common? The rise in uniqueness and individualism in Japan

Science.gov (United States)

Ogihara, Yuji; Fujita, Hiroyo; Tominaga, Hitoshi; Ishigaki, Sho; Kashimoto, Takuya; Takahashi, Ayano; Toyohara, Kyoko; Uchida, Yukiko

2015-01-01

We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. However, much of the past research did not account for the fact that culture is changing. Indeed, archival data on behavior (e.g., divorce rates) suggest a rise in individualism in the U.S. and Japan. In addition to archival data, cultural products (which express an individual’s psyche and behavior outside the head; e.g., advertising) can also reveal cultural change. However, little research has investigated the changes in individualism in East Asia using cultural products. To reveal the dynamic aspects of culture, it is important to present temporal data across cultures. In this study, we examined baby names as a cultural product. If Japanese culture has become more individualistic, parents would be expected to give their children unique names. Using two databases, we calculated the rate of popular baby names between 2004 and 2013. Both databases released the rankings of popular names and their rates within the sample. As Japanese names are generally comprised of both written Chinese characters and their pronunciations, we analyzed these two separately. We found that the rate of popular Chinese characters increased, whereas the rate of popular pronunciations decreased. However, only the rate of popular pronunciations was associated with a previously validated collectivism index. Moreover, we examined the pronunciation variation of common combinations of Chinese characters and the written form variation of common pronunciations. We found that the variation of written forms decreased, whereas the variation of pronunciations increased over time. Taken together, these results showed that parents are giving their children unique names by pairing common

Deciding where to attend: Large-scale network mechanisms underlying attention and intention revealed by graph-theoretic analysis.

Science.gov (United States)

Liu, Yuelu; Hong, Xiangfei; Bengson, Jesse J; Kelley, Todd A; Ding, Mingzhou; Mangun, George R

2017-08-15

The neural mechanisms by which intentions are transformed into actions remain poorly understood. We investigated the network mechanisms underlying spontaneous voluntary decisions about where to focus visual-spatial attention (willed attention). Graph-theoretic analysis of two independent datasets revealed that regions activated during willed attention form a set of functionally-distinct networks corresponding to the frontoparietal network, the cingulo-opercular network, and the dorsal attention network. Contrasting willed attention with instructed attention (where attention is directed by external cues), we observed that the dorsal anterior cingulate cortex was allied with the dorsal attention network in instructed attention, but shifted connectivity during willed attention to interact with the cingulo-opercular network, which then mediated communications between the frontoparietal network and the dorsal attention network. Behaviorally, greater connectivity in network hubs, including the dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and the inferior parietal lobule, was associated with faster reaction times. These results, shown to be consistent across the two independent datasets, uncover the dynamic organization of functionally-distinct networks engaged to support intentional acts. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo time-resolved microtomography reveals the mechanics of the blowfly flight motor.

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Simon M Walker

2014-03-01

Full Text Available Dipteran flies are amongst the smallest and most agile of flying animals. Their wings are driven indirectly by large power muscles, which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge. Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles acting directly on the wing articulations. Collectively the steering muscles account for <3% of total flight muscle mass, raising the question of how they can modulate the vastly greater output of the power muscles during manoeuvres. Here we present the results of a synchrotron-based study performing micrometre-resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies. These data represent the first four-dimensional visualizations of an organism's internal movements on sub-millisecond and micrometre scales. This technique allows us to visualize and measure the three-dimensional movements of five of the largest steering muscles, and to place these in the context of the deforming thoracic mechanism that the muscles actuate. Our visualizations show that the steering muscles operate through a diverse range of nonlinear mechanisms, revealing several unexpected features that could not have been identified using any other technique. The tendons of some steering muscles buckle on every wingbeat to accommodate high amplitude movements of the wing hinge. Other steering muscles absorb kinetic energy from an oscillating control linkage, which rotates at low wingbeat amplitude but translates at high wingbeat amplitude. Kinetic energy is distributed differently in these two modes of oscillation, which may play a role in asymmetric power management during flight control. Structural flexibility is known to be important to the aerodynamic efficiency of insect wings, and to the function of their indirect power muscles. We show that it is integral also to the operation of the steering muscles, and so to the functional flexibility of the

In vivo time-resolved microtomography reveals the mechanics of the blowfly flight motor.

Science.gov (United States)

Walker, Simon M; Schwyn, Daniel A; Mokso, Rajmund; Wicklein, Martina; Müller, Tonya; Doube, Michael; Stampanoni, Marco; Krapp, Holger G; Taylor, Graham K

2014-03-01

Dipteran flies are amongst the smallest and most agile of flying animals. Their wings are driven indirectly by large power muscles, which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge. Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles acting directly on the wing articulations. Collectively the steering muscles account for flight muscle mass, raising the question of how they can modulate the vastly greater output of the power muscles during manoeuvres. Here we present the results of a synchrotron-based study performing micrometre-resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies. These data represent the first four-dimensional visualizations of an organism's internal movements on sub-millisecond and micrometre scales. This technique allows us to visualize and measure the three-dimensional movements of five of the largest steering muscles, and to place these in the context of the deforming thoracic mechanism that the muscles actuate. Our visualizations show that the steering muscles operate through a diverse range of nonlinear mechanisms, revealing several unexpected features that could not have been identified using any other technique. The tendons of some steering muscles buckle on every wingbeat to accommodate high amplitude movements of the wing hinge. Other steering muscles absorb kinetic energy from an oscillating control linkage, which rotates at low wingbeat amplitude but translates at high wingbeat amplitude. Kinetic energy is distributed differently in these two modes of oscillation, which may play a role in asymmetric power management during flight control. Structural flexibility is known to be important to the aerodynamic efficiency of insect wings, and to the function of their indirect power muscles. We show that it is integral also to the operation of the steering muscles, and so to the functional flexibility of the insect flight motor.

The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

Directory of Open Access Journals (Sweden)

Qun Liu

2012-01-01

Full Text Available Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale. In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.

Comparative genomics of neuroglobin reveals its early origins.

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Jasmin Dröge

Full Text Available Neuroglobin (Ngb is a hexacoordinated globin expressed mainly in the central and peripheral nervous system of vertebrates. Although several hypotheses have been put forward regarding the role of neuroglobin, its definite function remains uncertain. Ngb appears to have a neuro-protective role enhancing cell viability under hypoxia and other types of oxidative stress. Ngb is phylogenetically ancient and has a substitution rate nearly four times lower than that of other vertebrate globins, e.g. hemoglobin. Despite its high sequence conservation among vertebrates Ngb seems to be elusive in invertebrates.We determined candidate orthologs in invertebrates and identified a globin of the placozoan Trichoplax adhaerens that is most likely orthologous to vertebrate Ngb and confirmed the orthologous relationship of the polymeric globin of the sea urchin Strongylocentrotus purpuratus to Ngb. The putative orthologous globin genes are located next to genes orthologous to vertebrate POMT2 similarly to localization of vertebrate Ngb. The shared syntenic position of the globins from Trichoplax, the sea urchin and of vertebrate Ngb strongly suggests that they are orthologous. A search for conserved transcription factor binding sites (TFBSs in the promoter regions of the Ngb genes of different vertebrates via phylogenetic footprinting revealed several TFBSs, which may contribute to the specific expression of Ngb, whereas a comparative analysis with myoglobin revealed several common TFBSs, suggestive of regulatory mechanisms common to globin genes.Identification of the placozoan and echinoderm genes orthologous to vertebrate neuroglobin strongly supports the hypothesis of the early evolutionary origin of this globin, as it shows that neuroglobin was already present in the placozoan-bilaterian last common ancestor. Computational determination of the transcription factor binding sites repertoire provides on the one hand a set of transcriptional factors that are

Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms.

Science.gov (United States)

Kanoski, S E; Ong, Z Y; Fortin, S M; Schlessinger, E S; Grill, H J

2015-03-01

To investigate the behavioural and intracellular mechanisms by which the glucagon like peptide-1 (GLP-1) receptor agonist, liraglutide, and leptin in combination enhance the food intake inhibitory and weight loss effects of either treatment alone. We examined the effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (s.c.) or to the third ventricle, respectively, on cumulative intake, meal patterns and hypothalamic expression of intracellular signalling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] in lean rats. A low-dose combination of liraglutide (25 µg/kg) and leptin (0.75 µg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75 µg/kg) and leptin (4 µg), examined separately, each reduced meal frequency, cumulative food intake and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot analysis showed elevated pSTAT3 in the hypothalamic tissue after liraglutide-leptin co-treatment, an effect which was greater than that of leptin treatment alone. In addition, s.c. liraglutide reduced the expression of PTP1B (a negative regulator of leptin receptor signalling), revealing a potential mechanism for the enhanced pSTAT3 response after liraglutide-leptin co-administration. Collectively, these results show novel behavioural and molecular mechanisms underlying the additive reduction in food intake and body weight after liraglutide-leptin combination treatment. © 2014 John Wiley & Sons Ltd.

Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

KAUST Repository

Bagchi, Samik

2016-06-20

Granules enriched with anammox bacteria are essential in enhancing the treatment of ammonia-rich wastewater, but little is known about how anammox bacteria grow and multiply inside granules. Here, we combined metatranscriptomics, quantitative PCR and 16S rRNA gene sequencing to study the changes in community composition, metabolic gene content and gene expression in a granular anammox reactor with the objective of understanding the molecular mechanism of anammox growth and multiplication that led to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all the essential transcripts for anammox metabolism. During the later stage of reactor operation, higher expression of ammonia and nitrite transport proteins and key metabolic enzymes mainly in the bottom large granules facilitated anammox bacteria activity. The high activity resulted in higher growth and multiplication of anammox bacteria and expanded the size of the granules. This conceptual model for large granule formation proposed here may assist in the future design of anammox processes for mainstream wastewater treatment.

The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

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Lorant Janosi

Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

Organising pneumonia in common variable immunodeficiency.

Science.gov (United States)

Boujaoude, Ziad; Arya, Rohan; Rafferty, William; Dammert, Pedro

2013-06-07

Common variable immunodeficiency (CVID) is the most common of the primary immunodeficiency disorders. Pulmonary manifestations are characterised by recurrent rhinosinusitis, respiratory tract infections and bronchiectasis. Less commonly the lung may be affected by lymphoid disorders and sarcoid-like granulomas. Organising pneumonia (OP) is a rare pulmonary manifestation. We report the case of a 32-year-old woman with CVID who presented with fever, dyspnoea and persistent lung infiltrates despite antibiotic therapy. CT of the chest showed bilateral patchy alveolar infiltrates. Pulmonary function tests revealed moderate restriction and reduction in diffusion capacity. Initial bronchoscopy with transbronchial biopsies did not yield a diagnosis but surgical lung biopsies identified OP. Significant clinical, radiographic and physiological improvement was achieved after institution of corticosteroid therapy.

The complete genome and proteome of Laribacter hongkongensis reveal potential mechanisms for adaptations to different temperatures and habitats.

Science.gov (United States)

Woo, Patrick C Y; Lau, Susanna K P; Tse, Herman; Teng, Jade L L; Curreem, Shirly O T; Tsang, Alan K L; Fan, Rachel Y Y; Wong, Gilman K M; Huang, Yi; Loman, Nicholas J; Snyder, Lori A S; Cai, James J; Huang, Jian-Dong; Mak, William; Pallen, Mark J; Lok, Si; Yuen, Kwok-Yung

2009-03-01

Laribacter hongkongensis is a newly discovered Gram-negative bacillus of the Neisseriaceae family associated with freshwater fish-borne gastroenteritis and traveler's diarrhea. The complete genome sequence of L. hongkongensis HLHK9, recovered from an immunocompetent patient with severe gastroenteritis, consists of a 3,169-kb chromosome with G+C content of 62.35%. Genome analysis reveals different mechanisms potentially important for its adaptation to diverse habitats of human and freshwater fish intestines and freshwater environments. The gene contents support its phenotypic properties and suggest that amino acids and fatty acids can be used as carbon sources. The extensive variety of transporters, including multidrug efflux and heavy metal transporters as well as genes involved in chemotaxis, may enable L. hongkongensis to survive in different environmental niches. Genes encoding urease, bile salts efflux pump, adhesin, catalase, superoxide dismutase, and other putative virulence factors-such as hemolysins, RTX toxins, patatin-like proteins, phospholipase A1, and collagenases-are present. Proteomes of L. hongkongensis HLHK9 cultured at 37 degrees C (human body temperature) and 20 degrees C (freshwater habitat temperature) showed differential gene expression, including two homologous copies of argB, argB-20, and argB-37, which encode two isoenzymes of N-acetyl-L-glutamate kinase (NAGK)-NAGK-20 and NAGK-37-in the arginine biosynthesis pathway. NAGK-20 showed higher expression at 20 degrees C, whereas NAGK-37 showed higher expression at 37 degrees C. NAGK-20 also had a lower optimal temperature for enzymatic activities and was inhibited by arginine probably as negative-feedback control. Similar duplicated copies of argB are also observed in bacteria from hot springs such as Thermus thermophilus, Deinococcus geothermalis, Deinococcus radiodurans, and Roseiflexus castenholzii, suggesting that similar mechanisms for temperature adaptation may be employed by other

Innate immune response against an oomycete pathogen Aphanomyces invadans in common carp (Cyprinus carpio), a fish resistant to epizootic ulcerative syndrome.

Science.gov (United States)

Yadav, Manoj K; Pradhan, Pravata K; Sood, Neeraj; Chaudhary, Dharmendra K; Verma, Dev K; Chauhan, U K; Punia, Peyush; Jena, Joy K

2016-03-01

Infection with Aphanomyces invadans, also known as epizootic ulcerative syndrome, is a destructive disease of freshwater and brackishwater fishes. Although more than 130 species of fish have been confirmed to be susceptible to this disease, some of the commercially important fish species like common carp, milk fish and tilapia are reported to be resistant. Species that are naturally resistant to a particular disease, provide a potential model to study the mechanisms of resistance against that disease. In the present study, following experimental infection with A. invadans in common carp Cyprinus carpio, sequential changes in various innate immune parameters and histopathological alterations were monitored. Some of the studied innate immunity parameters viz. respiratory burst, alternative complement and total antiproteases activities of the infected common carp were higher compared to control fish, particularly at early stages of infection. On the other hand, some parameters such as myeloperoxidase, lysozyme and alpha-2 macroglobulin activities were not altered. Histopathological examination of the muscle at the site of injection revealed well developed granulomas at 12 days post infection, with subsequent regeneration of muscle fibers. From the results, it could be inferred that innate defense mechanisms of common carp are able to neutralize the virulence factors secreted by A. invadans, thereby, preventing its invasive spread and containing the infection. The results obtained here will help to better understand the mechanisms underlying resistance against A. invadans infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Common cause failures of reactor pressure components

International Nuclear Information System (INIS)

Mankamo, T.

1978-01-01

The common cause failure is defined as a multiple failure event due to a common cause. The existence of common failure causes may ruin the potential advantages of applying redundancy for reliability improvement. Examples relevant to large mechanical components are presented. Preventive measures against common cause failures, such as physical separation, equipment diversity, quality assurance, and feedback from experience are discussed. Despite the large number of potential interdependencies, the analysis of common cause failures can be done within the framework of conventional reliability analysis, utilizing, for example, the method of deriving minimal cut sets from a system fault tree. Tools for the description and evaluation of dependencies between components are discussed: these include the model of conditional failure causes that are common to many components, and evaluation of the reliability of redundant components subjected to a common load. (author)

Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

Energy Technology Data Exchange (ETDEWEB)

Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria; Chiorazzo, Michael G.; Taylor, Ronald K.; Kull, F. Jon (Dartmouth)

2010-03-04

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.

Network Analysis Reveals a Common Host–Pathogen Interaction Pattern in Arabidopsis Immune Responses

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Hong Li

2017-05-01

Full Text Available Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein–protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs. We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant–pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

Science.gov (United States)

Hancks, Dustin C; Hartley, Melissa K; Hagan, Celia; Clark, Nathan L; Elde, Nels C

2015-05-01

A diverse subset of pattern recognition receptors (PRRs) detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS) was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA) from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1), a PRR that detects double-stranded RNA (dsRNA), despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system have adapted

Overlapping Patterns of Rapid Evolution in the Nucleic Acid Sensors cGAS and OAS1 Suggest a Common Mechanism of Pathogen Antagonism and Escape.

Directory of Open Access Journals (Sweden)

Dustin C Hancks

2015-05-01

Full Text Available A diverse subset of pattern recognition receptors (PRRs detects pathogen-associated nucleic acids to initiate crucial innate immune responses in host organisms. Reflecting their importance for host defense, pathogens encode various countermeasures to evade or inhibit these immune effectors. PRRs directly engaged by pathogen inhibitors often evolve under recurrent bouts of positive selection that have been described as molecular 'arms races.' Cyclic GMP-AMP synthase (cGAS was recently identified as a key PRR. Upon binding cytoplasmic double-stranded DNA (dsDNA from various viruses, cGAS generates the small nucleotide secondary messenger cGAMP to signal activation of innate defenses. Here we report an evolutionary history of cGAS with recurrent positive selection in the primate lineage. Recent studies indicate a high degree of structural similarity between cGAS and 2'-5'-oligoadenylate synthase 1 (OAS1, a PRR that detects double-stranded RNA (dsRNA, despite low sequence identity between the respective genes. We present comprehensive comparative evolutionary analysis of cGAS and OAS1 primate sequences and observe positive selection at nucleic acid binding interfaces and distributed throughout both genes. Our data revealed homologous regions with strong signatures of positive selection, suggesting common mechanisms employed by unknown pathogen encoded inhibitors and similar modes of evasion from antagonism. Our analysis of cGAS diversification also identified alternately spliced forms missing multiple sites under positive selection. Further analysis of selection on the OAS family in primates, which comprises OAS1, OAS2, OAS3 and OASL, suggests a hypothesis where gene duplications and domain fusion events result in paralogs that provide another means of escaping pathogen inhibitors. Together our comparative evolutionary analysis of cGAS and OAS provides new insights into distinct mechanisms by which key molecular sentinels of the innate immune system

Transgenic Analysis of the Leishmania MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability

DEFF Research Database (Denmark)

Cayla, M.; Rachidi, N.; Leclercq, O.

2014-01-01

Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying parasite development remain largely elusive even...... though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10). Using a transgenic approach, we demonstrate that MPK10 is stage...... at position 395 that could be implicated in kinase regulation. Finally, we uncovered a feedback loop that limits MPK10 activity through dephosphorylation of the tyrosine residue of the TxY motif. Together our data reveal novel aspects of protein kinase regulation in Leishmania, and propose MPK10...

Cycles and Common Cycles in Property and Related Sectors

OpenAIRE

Peijie Wang

2003-01-01

This paper examines cycles and common cycles in the property market and the economy. While focusing on common cycles, the study also incorporates common trends in the meantime, so it covers the whole spectrum of dynamic analysis. It has been found that property shares common cycles, particularly with those sectors that are the user markets of property. The mechanisms of common cycles and the relative magnitudes of cycles of the sectors related to property are discussed to shed light on proper...

Mechanical stop mechanism for overcoming MEMS fabrication tolerances

International Nuclear Information System (INIS)

Hussein, Hussein; Bourbon, Gilles; Le Moal, Patrice; Lutz, Philippe; Haddab, Yassine

2017-01-01

A mechanical stop mechanism is developed in order to compensate MEMS fabrication tolerances in discrete positioning. The mechanical stop mechanism is designed to be implemented on SOI wafers using a common DRIE etching process. The various fabrication tolerances obtained due to the etching process are presented and discussed in the paper. The principle and design of the mechanism are then presented. Finally, experiments on microfabricated positioning prototypes show accurate steps unaffected by the fabrication tolerances. (technical note)

Common Visual Preference for Curved Contours in Humans and Great Apes.

Science.gov (United States)

Munar, Enric; Gómez-Puerto, Gerardo; Call, Josep; Nadal, Marcos

2015-01-01

Among the visual preferences that guide many everyday activities and decisions, from consumer choices to social judgment, preference for curved over sharp-angled contours is commonly thought to have played an adaptive role throughout human evolution, favoring the avoidance of potentially harmful objects. However, because nonhuman primates also exhibit preferences for certain visual qualities, it is conceivable that humans' preference for curved contours is grounded on perceptual and cognitive mechanisms shared with extant nonhuman primate species. Here we aimed to determine whether nonhuman great apes and humans share a visual preference for curved over sharp-angled contours using a 2-alternative forced choice experimental paradigm under comparable conditions. Our results revealed that the human group and the great ape group indeed share a common preference for curved over sharp-angled contours, but that they differ in the manner and magnitude with which this preference is expressed behaviorally. These results suggest that humans' visual preference for curved objects evolved from earlier primate species' visual preferences, and that during this process it became stronger, but also more susceptible to the influence of higher cognitive processes and preference for other visual features.

Common variable immunodeficiency in a horse.

Science.gov (United States)

Flaminio, M Julia B F; LaCombe, Veronique; Kohn, Catherine W; Antczak, Douglas F

2002-11-01

A 12-year-old Quarter Horse mare that was nonresponsive to medical treatment was evaluated for chronic respiratory disease and hepatobiliary disease. Serum immunoglobulin concentrations were measured by use of radial immunodiffusion that revealed trace to nondetectable concentrations of IgG, IgG(T), IgM, and IgA. Use of serum protein electrophoresis confirmed agammaglobulinemia by the absence of the expected peak in the gamma region. In addition, vaccination with tetanus toxoid did not result in specific immunoglobulin production. Flow cytometric analysis of blood lymphocyte subpopulations revealed the absence of B cells in blood. Immunohistochemical analysis of tissue sections revealed the absence of B lymphocytes in bone marrow and spleen, with occasional B cells in the peripheral lymph nodes. Blood lymphocyte proliferation assays revealed weak responses to pokeweed mitogen and no response to stimulation with lipopolysaccharide. Considering the age and sex of the horse, results of the immunologic tests suggested a diagnosis of common variable immunodeficiency.

Genome-wide maps of alkylation damage, repair, and mutagenesis in yeast reveal mechanisms of mutational heterogeneity.

Science.gov (United States)

Mao, Peng; Brown, Alexander J; Malc, Ewa P; Mieczkowski, Piotr A; Smerdon, Michael J; Roberts, Steven A; Wyrick, John J

2017-10-01

DNA base damage is an important contributor to genome instability, but how the formation and repair of these lesions is affected by the genomic landscape and contributes to mutagenesis is unknown. Here, we describe genome-wide maps of DNA base damage, repair, and mutagenesis at single nucleotide resolution in yeast treated with the alkylating agent methyl methanesulfonate (MMS). Analysis of these maps revealed that base excision repair (BER) of alkylation damage is significantly modulated by chromatin, with faster repair in nucleosome-depleted regions, and slower repair and higher mutation density within strongly positioned nucleosomes. Both the translational and rotational settings of lesions within nucleosomes significantly influence BER efficiency; moreover, this effect is asymmetric relative to the nucleosome dyad axis and is regulated by histone modifications. Our data also indicate that MMS-induced mutations at adenine nucleotides are significantly enriched on the nontranscribed strand (NTS) of yeast genes, particularly in BER-deficient strains, due to higher damage formation on the NTS and transcription-coupled repair of the transcribed strand (TS). These findings reveal the influence of chromatin on repair and mutagenesis of base lesions on a genome-wide scale and suggest a novel mechanism for transcription-associated mutation asymmetry, which is frequently observed in human cancers. © 2017 Mao et al.; Published by Cold Spring Harbor Laboratory Press.

Comparative proteomic and metabolomic analysis reveal the antiosteoporotic molecular mechanism of icariin from Epimedium brevicornu maxim.

Science.gov (United States)

Xue, Liming; Jiang, Yiping; Han, Ting; Zhang, Naidan; Qin, Luping; Xin, Hailiang; Zhang, Qiaoyan

2016-11-04

Icariin, a principal flavonoid glycoside of Epimedium brevicornu Maxim, has been widely proved to possess antiosteoporotic activity with promoting bone formation and decreasing bone resorption. However, the involving mechanisms remain unclear. To clear a global insight of signal pathways involved in anti-osteoporotic mechanism of icariin at proteins and metabolites level by integrating the proteomics and NMR metabonomics, in a systems biology approach. Mice were divided into sham, OVX model and icariin-treated OVX group, after 90 days treatment, difference gel electrophoresis combined with MALDI-TOF/TOF proteomics analysis on bone femur and serum metabolomics were carried out for monitor intracellular processes and elucidate anti-osteoporotic mechanism of icariin. Osteoblast and osteoclast were applied to evaluate the potential signal pathways. Twenty three proteins in bone femur, and 8 metabolites in serum, were significantly altered and identified, involving in bone remodeling, energy metabolism, cytoskeleton, lipid metabolism, MAPK signaling, Ca 2+ signaling et, al. Furthermore, animal experiment show icariin could enhance the BMD and BMC, decrease CTX-I level in ovariectomized mice. The mitochondrial membrane potential and the intracellular ATP levels were increased significantly, and the cytoskeleton were improved in icariin-treatment osteoblast and osteoclast. Icariin also increased mRNA expression of Runx2 and osterix of OB, decreased CTR and CAII mRNA expression and protein expression of P38 and JNK. However, icariin did not reveal any inhibition of the collagenolytic activity of cathepsin K, mRNA expression of MMP-9 and protein expression of ERK in osteoclast. we consider icariin as multi-targeting compounds for treating with osteoporosis, involve initiating osteoblastogenesis, inhibiting adipogenesis, and preventing osteoclast differentiation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Subsurface damage mechanism of high speed grinding process in single crystal silicon revealed by atomistic simulations

International Nuclear Information System (INIS)

Li, Jia; Fang, Qihong; Zhang, Liangchi; Liu, Youwen

2015-01-01

stress status. The dislocation nucleation and motion induced plastic deformation during grinding process can better reveal subsurface damage mechanism considering to stress and temperature acting on the dislocations

Mechanical properties of ultra thin metallic films revealed by synchrotron techniques

Energy Technology Data Exchange (ETDEWEB)

Gruber, Patric Alfons

2007-07-20

A prerequisite for the study of the scaling behavior of mechanical properties of ultra thin films is a suitable testing technique. Therefore synchrotron-based in situ testing techniques were developed and optimized in order to characterize the stress evolution in ultra thin metallic films on compliant polymer substrates during isothermal tensile tests. Experimental procedures for polycrystalline as well as single crystalline films were established. These techniques were used to systematically investigate the influence of microstructure, film thickness (20 to 1000 nm) and temperature (-150 to 200 C) on the mechanical properties. Passivated and unpassivated Au and Cu films as well as single crystalline Au films on polyimide substrates were tested. Special care was also dedicated to the microstructural characterization of the samples which was very important for the correct interpretation of the results of the mechanical tests. Down to a film thickness of about 100 to 200 nm the yield strength increased for all film systems (passivated and unpassivated) and microstructures (polycrystalline and singlecrystalline). The influence of different interfaces was smaller than expected. This could be explained by a dislocation source model based on the nucleation of perfect dislocations. For polycrystalline films the film thickness as well as the grain size distribution had to be considered. For smaller film thicknesses the increase in flow stress was weaker and the deformation behavior changed because the nucleation of perfect dislocations became unfavorable. Instead, the film materials used alternative mechanisms to relieve the high stresses. For regular and homogeneous deformation the total strain was accommodated by the nucleation and motion of partial dislocations. If the deformation was localized due to initial cracks in a brittle interlayer or local delamination, dislocation plasticity was not effective enough to relieve the stress concentration and the films showed

Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

Science.gov (United States)

Yang, Kai-Chien; Yamada, Kathryn A; Patel, Akshar Y; Topkara, Veli K; George, Isaac; Cheema, Faisal H; Ewald, Gregory A; Mann, Douglas L; Nerbonne, Jeanne M

2014-03-04

Microarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). Deep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs. The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

Science.gov (United States)

Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

2017-01-24

Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

Biospectroscopy reveals the effect of varying water quality on tadpole tissues of the common frog (Rana temporaria).

Science.gov (United States)

Strong, Rebecca J; Halsall, Crispin J; Ferenčík, Martin; Jones, Kevin C; Shore, Richard F; Martin, Francis L

2016-06-01

Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog (Rana temporaria) tadpoles collected from ponds with differing water quality. Small differences in spectral signatures were revealed between a rural agricultural pond and an urban pond receiving wastewater and landfill run-off; these were limited to the liver and heart, although large differences in body size were apparent, surprisingly with tadpoles from the urban site larger than those from the rural site. Large differences in liver spectra were found between tadpoles from the pesticide and nutrient impacted pond compared to the rural agricultural pond, particularly in regions associated with lipids. Liver mass and hepatosomatic indices were found to be significantly increased in tadpoles from the site impacted by pesticides and trace organic chemicals, suggestive of exposure to environmental contamination. Significant alterations were also found in muscle tissue between tadpoles from these two ponds in regions associated with glycogen, potentially indicative of a stress response. This study highlights the use of IR spectroscopy, a low-cost, rapid and reagent-free technique in the biomonitoring of a class of organisms susceptible to environmental degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices.

Science.gov (United States)

Zanuy, David; Gunasekaran, Kannan; Lesk, Arthur M; Nussinov, Ruth

2006-04-21

The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Here, we model peptides rich in glutamine, through a series of molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and of a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments linked by planar turns or bends. Interestingly, our comprehensive analysis of the Protein Data Bank reveals that this is a common motif in beta-helices (termed beta-bend), although it has not been identified so far. The motif is based on the alternation of beta-sheet and helical conformation as the protein sequence is followed from the N to the C termini (beta-alpha(R)-beta-polyPro-beta). We further identify this motif in the ssNMR structure of the protofibril of the amyloidogenic peptide Abeta(1-40). The recurrence of the beta-bend suggests a general mode of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures. The design allows the peptide backbone to change direction with a minimal loss of main chain hydrogen bonds. The identification of a coherent organization beyond that of the beta-sheet segments in different folds rich in parallel beta-sheets suggests a higher degree of ordered structure in protein fibrils, in agreement with their low solubility and dense molecular packing.

The agricultural policy of Serbia and common agricultural policy

Directory of Open Access Journals (Sweden)

Stanković Milica

2012-01-01

Full Text Available The agricultural sector has a relatively high importance in the economic structure of Serbia. The Common Agricultural Policy (CAP, Common Agricultural Policy is one of the main policies of the European Union. It is very important to point out the fundamental principles and objectives of the Common Agricultural Policy. Harmonization of the national agricultural policy of Serbia with the Common Agricultural Policy and acceptance of its mechanisms is crucial for the development of the agricultural sector as a whole.

Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate

Science.gov (United States)

Mangold, Elisabeth; Böhmer, Anne C.; Ishorst, Nina; Hoebel, Ann-Kathrin; Gültepe, Pinar; Schuenke, Hannah; Klamt, Johanna; Hofmann, Andrea; Gölz, Lina; Raff, Ruth; Tessmann, Peter; Nowak, Stefanie; Reutter, Heiko; Hemprich, Alexander; Kreusch, Thomas; Kramer, Franz-Josef; Braumann, Bert; Reich, Rudolf; Schmidt, Gül; Jäger, Andreas; Reiter, Rudolf; Brosch, Sibylle; Stavusis, Janis; Ishida, Miho; Seselgyte, Rimante; Moore, Gudrun E.; Nöthen, Markus M.; Borck, Guntram; Aldhorae, Khalid A.; Lace, Baiba; Stanier, Philip; Knapp, Michael; Ludwig, Kerstin U.

2016-01-01

Nonsyndromic cleft lip with/without cleft palate (nsCL/P) and nonsyndromic cleft palate only (nsCPO) are the most frequent subphenotypes of orofacial clefts. A common syndromic form of orofacial clefting is Van der Woude syndrome (VWS) where individuals have CL/P or CPO, often but not always associated with lower lip pits. Recently, ∼5% of VWS-affected individuals were identified with mutations in the grainy head-like 3 gene (GRHL3). To investigate GRHL3 in nonsyndromic clefting, we sequenced its coding region in 576 Europeans with nsCL/P and 96 with nsCPO. Most strikingly, nsCPO-affected individuals had a higher minor allele frequency for rs41268753 (0.099) than control subjects (0.049; p = 1.24 × 10−2). This association was replicated in nsCPO/control cohorts from Latvia, Yemen, and the UK (pcombined = 2.63 × 10−5; ORallelic = 2.46 [95% CI 1.6–3.7]) and reached genome-wide significance in combination with imputed data from a GWAS in nsCPO triads (p = 2.73 × 10−9). Notably, rs41268753 is not associated with nsCL/P (p = 0.45). rs41268753 encodes the highly conserved p.Thr454Met (c.1361C>T) (GERP = 5.3), which prediction programs denote as deleterious, has a CADD score of 29.6, and increases protein binding capacity in silico. Sequencing also revealed four novel truncating GRHL3 mutations including two that were de novo in four families, where all nine individuals harboring mutations had nsCPO. This is important for genetic counseling: given that VWS is rare compared to nsCPO, our data suggest that dominant GRHL3 mutations are more likely to cause nonsyndromic than syndromic CPO. Thus, with rare dominant mutations and a common risk variant in the coding region, we have identified an important contribution for GRHL3 in nsCPO. PMID:27018475

Mechanics of machinery

CERN Document Server

Mostafa, Mahmoud A

2012-01-01

MechanismsDefinitions Degrees of Freedom of Planar Mechanisms Four-Revolute-Pairs Chains Single-Slider Chain Double-Slider Mechanisms Mechanisms with Higher Pairs Compound Mechanisms Special Mechanisms Analytical Position Analysis of Mechanisms Velocities and AccelerationsAbsolute Plane Motion of a Particle Relative Motion Applications to Common Links Analysis of Mechanisms: Graphical Method Method of Instantaneous Centers for Determining the VelocitiesAnalytical Analysis CamsIntroduction Types of Cams Modes of Input/Output Motion Follower Configurations Classes of Cams Spur GearsIntroduction

Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

Directory of Open Access Journals (Sweden)

Taiga Miyazaki

2013-01-01

Full Text Available Proper protein folding in the endoplasmic reticulum (ER is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR, is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata.

Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients.

Directory of Open Access Journals (Sweden)

Ashley D Smith

Full Text Available The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients.

Resilience of honeybee colonies via common stomach: A model of self-regulation of foraging.

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Thomas Schmickl

Full Text Available We propose a new regulation mechanism based on the idea of the "common stomach" to explain several aspects of the resilience and homeostatic regulation of honeybee colonies. This mechanism exploits shared pools of substances (pollen, nectar, workers, brood that modulate recruitment, abandonment and allocation patterns at the colony-level and enable bees to perform several survival strategies to cope with difficult circumstances: Lack of proteins leads to reduced feeding of young brood, to early capping of old brood and to regaining of already spent proteins through brood cannibalism. We modeled this system by linear interaction terms and mass-action law. To test the predictive power of the model of this regulatory mechanism we compared our model predictions to experimental data of several studies. These comparisons show that the proposed regulation mechanism can explain a variety of colony level behaviors. Detailed analysis of the model revealed that these mechanisms could explain the resilience, stability and self-regulation observed in honeybee colonies. We found that manipulation of material flow and applying sudden perturbations to colony stocks are quickly compensated by a resulting counter-acting shift in task selection. Selective analysis of feedback loops allowed us to discriminate the importance of different feedback loops in self-regulation of honeybee colonies. We stress that a network of simple proximate mechanisms can explain significant colony-level abilities that can also be seen as ultimate reasoning of the evolutionary trajectory of honeybees.

A reformulation of mechanics and electrodynamics.

Science.gov (United States)

Pinheiro, Mario J

2017-07-01

Classical mechanics, as commonly taught in engineering and science, are confined to the conventional Newtonian theory. But classical mechanics has not really changed in substance since Newton formulation, describing simultaneous rotation and translation of objects with somewhat complicate drawbacks, risking interpretation of forces in non-inertial frames. In this work we introduce a new variational principle for out-of-equilibrium, rotating systems, obtaining a set of two first order differential equations that introduces a thermodynamic-mechanistic time into Newton's dynamical equation, and revealing the same formal symplectic structure shared by classical mechanics, fluid mechanics and thermodynamics. The results is a more consistent formulation of dynamics and electrodynamics, explaining natural phenomena as the outcome from a balance between energy and entropy, embedding translational with rotational motion into a single equation, showing centrifugal and Coriolis force as derivatives from the transport of angular momentum, and offering a natural method to handle variational problems, as shown with the brachistochrone problem. In consequence, a new force term appears, the topological torsion current, important for spacecraft dynamics. We describe a set of solved problems showing the potential of a competing technique, with significant interest to electrodynamics as well. We expect this new approach to have impact in a large class of scientific and technological problems.

High-resolution mapping reveals linkage between genes in common bean cultivar Ouro Negro conferring resistance to the rust, anthracnose, and angular leaf spot diseases.

Science.gov (United States)

Valentini, Giseli; Gonçalves-Vidigal, Maria Celeste; Hurtado-Gonzales, Oscar P; de Lima Castro, Sandra Aparecida; Cregan, Perry B; Song, Qijian; Pastor-Corrales, Marcial A

2017-08-01

Co-segregation analysis and high-throughput genotyping using SNP, SSR, and KASP markers demonstrated genetic linkage between Ur-14 and Co-3 4 /Phg-3 loci conferring resistance to the rust, anthracnose and angular leaf spot diseases of common bean. Rust, anthracnose, and angular leaf spot are major diseases of common bean in the Americas and Africa. The cultivar Ouro Negro has the Ur-14 gene that confers broad spectrum resistance to rust and the gene cluster Co-3 4 /Phg-3 containing two tightly linked genes conferring resistance to anthracnose and angular leaf spot, respectively. We used co-segregation analysis and high-throughput genotyping of 179 F 2:3 families from the Rudá (susceptible) × Ouro Negro (resistant) cross-phenotyped separately with races of the rust and anthracnose pathogens. The results confirmed that Ur-14 and Co-3 4 /Phg-3 cluster in Ouro Negro conferred resistance to rust and anthracnose, respectively, and that Ur-14 and the Co-3 4 /Phg-3 cluster were closely linked. Genotyping the F 2:3 families, first with 5398 SNPs on the Illumina BeadChip BARCBEAN6K_3 and with 15 SSR, and eight KASP markers, specifically designed for the candidate region containing Ur-14 and Co-3 4 /Phg-3, permitted the creation of a high-resolution genetic linkage map which revealed that Ur-14 was positioned at 2.2 cM from Co-3 4 /Phg-3 on the short arm of chromosome Pv04 of the common bean genome. Five flanking SSR markers were tightly linked at 0.1 and 0.2 cM from Ur-14, and two flanking KASP markers were tightly linked at 0.1 and 0.3 cM from Co-3 4 /Phg-3. Many other SSR, SNP, and KASP markers were also linked to these genes. These markers will be useful for the development of common bean cultivars combining the important Ur-14 and Co-3 4 /Phg-3 genes conferring resistance to three of the most destructive diseases of common bean.

A Rare Disorder with Common Clinical Presentation: Neonatal Bartter Syndrome.

Science.gov (United States)

Hussain, Shabbir; Tarar, Saba Haider; Al-Muhaizae, Muhammad

2015-04-01

Bartter syndrome is an autosomal recessive renal tubulopathy that presents with hypokalemic, hypochloremic metabolic alkalosis associated with increased urinary loss of sodium, potassium, calcium and chloride. There is hyperreninemia and hyperaldosteronemia but normotension. A full term male neonate was referred at 20-day of age with features of sepsis and respiratory distress. He was evaluated and managed as case of septicemia with all supportive paraphernalia including mechanical ventilation. Investigations revealed electrolytes imbalance and metabolic alkalosis suggestive of Neonatal Bartter Syndrome (NBS). Raised aldosterone and renin levels confirmed the diagnosis. Electrolyte imbalance was corrected with fluids and indomethacin, treated successfully, discharged and parents counseled. He was thriving well at 9 months of age. Another 2 months old male baby presented with recurrent episodes of lethargy with dehydration and failure to gain weight. Investigations confirmed the diagnosis of NBS. He was also successfully treated with same medication. We report these 2 cases because of the rarity of NBS, presentation of which may mimic common illnesses like sepsis and gastroenteritis.

Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

Science.gov (United States)

Samuel, Varman T.; Shulman, Gerald I.

2012-01-01

Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing

Science.gov (United States)

Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling

2016-10-01

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

Transcriptomics and in vivo tests reveal novel mechanisms underlying endocrine disruption in an ecological sentinel, Nucella lapillus.

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Pascoal, Sonia; Carvalho, Gary; Vasieva, Olga; Hughes, Roger; Cossins, Andrew; Fang, Yongxiang; Ashelford, Kevin; Olohan, Lisa; Barroso, Carlos; Mendo, Sonia; Creer, Simon

2013-03-01

Anthropogenic endocrine disruptors now contaminate all environments globally, with concomitant deleterious effects across diverse taxa. While most studies on endocrine disruption (ED) have focused on vertebrates, the superimposition of male sexual characteristics in the female dogwhelk, Nucella lapillus (imposex), caused by organotins, provides one of the most clearcut ecological examples of anthropogenically induced ED in aquatic ecosystems. To identify the underpinning mechanisms of imposex for this 'nonmodel' species, we combined Roche 454 pyrosequencing with custom oligoarray fabrication inexpensively to both generate gene models and identify those responding to chronic tributyltin (TBT) treatment. The results supported the involvement of steroid, neuroendocrine peptide hormone dysfunction and retinoid mechanisms, but suggested additionally the involvement of putative peroxisome proliferator-activated receptor (PPAR) pathways. Application of rosiglitazone, a well-known vertebrate PPARγ ligand, to dogwhelks induced imposex in the absence of TBT. Thus, while TBT-induced imposex is linked to the induction of many genes and has a complex phenotype, it is likely also to be driven by PPAR-responsive pathways, hitherto not described in invertebrates. Our findings provide further evidence for a common signalling pathway between invertebrate and vertebrate species that has previously been overlooked in the study of endocrine disruption. © 2012 Blackwell Publishing Ltd.

Memory, reasoning, and categorization: parallels and common mechanisms.

Science.gov (United States)

Hayes, Brett K; Heit, Evan; Rotello, Caren M

2014-01-01

Traditionally, memory, reasoning, and categorization have been treated as separate components of human cognition. We challenge this distinction, arguing that there is broad scope for crossover between the methods and theories developed for each task. The links between memory and reasoning are illustrated in a review of two lines of research. The first takes theoretical ideas (two-process accounts) and methodological tools (signal detection analysis, receiver operating characteristic curves) from memory research and applies them to important issues in reasoning research: relations between induction and deduction, and the belief bias effect. The second line of research introduces a task in which subjects make either memory or reasoning judgments for the same set of stimuli. Other than broader generalization for reasoning than memory, the results were similar for the two tasks, across a variety of experimental stimuli and manipulations. It was possible to simultaneously explain performance on both tasks within a single cognitive architecture, based on exemplar-based comparisons of similarity. The final sections explore evidence for empirical and processing links between inductive reasoning and categorization and between categorization and recognition. An important implication is that progress in all three of these fields will be expedited by further investigation of the many commonalities between these tasks.

Memory, reasoning and categorization: Parallels and common mechanisms

Directory of Open Access Journals (Sweden)

BRETT eHAYES

2014-06-01

Full Text Available Traditionally, memory, reasoning and categorization have been treated as separate components of human cognition. We challenge this distinction, arguing that there is broad scope for crossover between the methods and theories developed for each task. The links between memory and reasoning are illustrated in a review of two lines of research. The first takes theoretical ideas (two-process accounts and methodological tools (signal detection analysis, receiver operating characteristic curves from memory research and applies them to important issues in reasoning research: relations between induction and deduction, and the belief bias effect. The second line of research introduces a task in which subjects make either memory or reasoning judgments for the same set of stimuli. Other than broader generalization for reasoning than memory, the results were similar for the two tasks, across a variety of experimental stimuli and manipulations. It was possible to simultaneously explain performance on both tasks within a single cognitive architecture, based on exemplar-based comparisons of similarity. The final sections explore evidence for empirical and processing links between inductive reasoning and categorization and between categorization and recognition. An important implication is that progress in all three of these fields will be expedited by further investigation of the many commonalities between these tasks.

Biochemical Analysis Reveals the Multifactorial Mechanism of Histone H3 Clipping by Chicken Liver Histone H3 Protease

KAUST Repository

Chauhan, Sakshi

2016-09-02

Proteolytic clipping of histone H3 has been identified in many organisms. Despite several studies, the mechanism of clipping, the substrate specificity, and the significance of this poorly understood epigenetic mechanism are not clear. We have previously reported histone H3 specific proteolytic clipping and a protein inhibitor in chicken liver. However, the sites of clipping are still not known very well. In this study, we attempt to identify clipping sites in histone H3 and to determine the mechanism of inhibition by stefin B protein, a cysteine protease inhibitor. By employing site-directed mutagenesis and in vitro biochemical assays, we have identified three distinct clipping sites in recombinant human histone H3 and its variants (H3.1, H3.3, and H3t). However, post-translationally modified histones isolated from chicken liver and Saccharomyces cerevisiae wild-type cells showed different clipping patterns. Clipping of histone H3 N-terminal tail at three sites occurs in a sequential manner. We have further observed that clipping sites are regulated by the structure of the N-terminal tail as well as the globular domain of histone H3. We also have identified the QVVAG region of stefin B protein to be very crucial for inhibition of the protease activity. Altogether, our comprehensive biochemical studies have revealed three distinct clipping sites in histone H3 and their regulation by the structure of histone H3, histone modifications marks, and stefin B.

Active nuclear transcriptome analysis reveals inflammasome-dependent mechanism for early neutrophil response to Mycobacterium marinum.

Science.gov (United States)

Kenyon, Amy; Gavriouchkina, Daria; Zorman, Jernej; Napolitani, Giorgio; Cerundolo, Vincenzo; Sauka-Spengler, Tatjana

2017-07-26

The mechanisms governing neutrophil response to Mycobacterium tuberculosis remain poorly understood. In this study we utilise biotagging, a novel genome-wide profiling approach based on cell type-specific in vivo biotinylation in zebrafish to analyse the initial response of neutrophils to Mycobacterium marinum, a close genetic relative of M. tuberculosis used to model tuberculosis. Differential expression analysis following nuclear RNA-seq of neutrophil active transcriptomes reveals a significant upregulation in both damage-sensing and effector components of the inflammasome, including caspase b, NLRC3 ortholog (wu: fb15h11) and il1β. Crispr/Cas9-mediated knockout of caspase b, which acts by proteolytic processing of il1β, results in increased bacterial burden and less infiltration of macrophages to sites of mycobacterial infection, thus impairing granuloma development. We also show that a number of immediate early response genes (IEGs) are responsible for orchestrating the initial neutrophil response to mycobacterial infection. Further perturbation of the IEGs exposes egr3 as a key transcriptional regulator controlling il1β transcription.

Radiation-induced bilateral common carotid artery stenosis

International Nuclear Information System (INIS)

Kobayashi, Nobuaki; Nakagawa, Yoku; Tashiro, Kunio; Abe, Hiroshi

1986-01-01

A case of radiation-induced bilateral common carotid artery stenosis is reported. This 60 years old housewife was hospitalized in 1982 because of sudden onset of mild left hemiparesis. Twenty-five years ago, she underwent radiation therapy of approximately 5,000 rads to the anterior cervical region because of thyroid cancer. Angiograms in 1982 revealed bilateral common carotid artery stenosis, especially in the right common carotid artery, the legion of which were included within the field of radiation performed in 1952. Right thromboendarterectomy was performed in 1983. At operation, slight periarterial fibrosis with calcified arteriosclerotic change was found, and dissection between the thickened intima and the media was not so difficult. Histological change of resected thromboendarterium was similar to the one observed in the pure arteriosclerotic disease. (author)

The Common Forces: Conservative or Nonconservative?

Science.gov (United States)

Keeports, David

2006-01-01

Of the forces commonly encountered when solving problems in Newtonian mechanics, introductory texts usually limit illustrations of the definitions of conservative and nonconservative forces to gravity, spring forces, kinetic friction and fluid resistance. However, at the expense of very little class time, the question of whether each of the common…

Transcriptome analysis of the digestive system of a wood-feeding termite (Coptotermes formosanus) revealed a unique mechanism for effective biomass degradation.

Science.gov (United States)

Geng, Alei; Cheng, Yanbing; Wang, Yongli; Zhu, Daochen; Le, Yilin; Wu, Jian; Xie, Rongrong; Yuan, Joshua S; Sun, Jianzhong

2018-01-01

Wood-feeding termite, Coptotermes formosanus Shiraki, represents a highly efficient system for biomass deconstruction and utilization. However, the detailed mechanisms of lignin modification and carbohydrate degradation in this system are still largely elusive. In order to reveal the inherent mechanisms for efficient biomass degradation, four different organs (salivary glands, foregut, midgut, and hindgut) within a complete digestive system of a lower termite, C. formosanus , were dissected and collected. Comparative transcriptomics was carried out to analyze these organs using high-throughput RNA sequencing. A total of 71,117 unigenes were successfully assembled, and the comparative transcriptome analyses revealed significant differential distributions of GH (glycosyl hydrolase) genes and auxiliary redox enzyme genes in different digestive organs. Among the GH genes in the salivary glands, the most abundant were GH9, GH22, and GH1 genes. The corresponding enzymes may have secreted into the foregut and midgut to initiate the hydrolysis of biomass and to achieve a lignin-carbohydrate co-deconstruction system. As the most diverse GH families, GH7 and GH5 were primarily identified from the symbiotic protists in the hindgut. These enzymes could play a synergistic role with the endogenous enzymes from the host termite for biomass degradation. Moreover, twelve out of fourteen genes coding auxiliary redox enzymes from the host termite origin were induced by the feeding of lignin-rich diets. This indicated that these genes may be involved in lignin component deconstruction with its redox network during biomass pretreatment. These findings demonstrate that the termite digestive system synergized the hydrolysis and redox reactions in a programmatic process, through different parts of its gut system, to achieve a maximized utilization of carbohydrates. The detailed unique mechanisms identified from the termite digestive system may provide new insights for advanced design of

Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder.

Science.gov (United States)

Schulz, Kurt P; Fan, Jin; Bédard, Anne-Claude V; Clerkin, Suzanne M; Ivanov, Iliyan; Tang, Cheuk Y; Halperin, Jeffrey M; Newcorn, Jeffrey H

2012-09-01

CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallel-groups design. SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. PARTICIPANTS Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. RESULTS Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. CONCLUSIONS Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic

A Common Mechanism Underlying Food Choice and Social Decisions

Science.gov (United States)

Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

2015-01-01

People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others’ benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making. PMID:26460812

A Common Mechanism Underlying Food Choice and Social Decisions.

Science.gov (United States)

Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

2015-10-01

People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

Mechanisms of population heterogeneity among molting common mergansers on Kodiak Island, Alaska: Implications for genetic assessments of migratory connectivity

Science.gov (United States)

Pearce, John M.; Zwiefelhofer, Denny; Maryanski, Nate

2009-01-01

Quantifying population genetic heterogeneity within nonbreeding aggregations can inform our understanding of patterns of site fidelity, migratory connectivity, and gene flow between breeding and nonbreeding areas. However, characterizing mechanisms that contribute to heterogeneity, such as migration and dispersal, is required before site fidelity and migratory connectivity can be assessed accurately. We studied nonbreeding groups of Common Mergansers (Mergus merganser) molting on Kodiak Island, Alaska, from 2005 to 2007, using banding data to assess rates of recapture, mitochondrial (mt) DNA to determine natal area, and nuclear microsatellite genotypes to assess dispersal. Using baseline information from differentiated mtDNA haplogroups across North America, we were able to assign individuals to natal regions and document population genetic heterogeneity within and among molting groups. Band-recovery and DNA data suggest that both migration from and dispersal among natal areas contribute to admixed groups of males molting on Kodiak Island. A lack of differentiation in the Common Merganser's nuclear, bi-parentally inherited DNA, observed across North America, implies that dispersal can mislead genetic assessments of migratory connectivity and assignments of nonbreeding individuals to breeding areas. Thus multiple and independent data types are required to account for such behaviors before accurate assessments of migratory connectivity can be made.

Lightning attachment process to common buildings

Science.gov (United States)

Saba, M. M. F.; Paiva, A. R.; Schumann, C.; Ferro, M. A. S.; Naccarato, K. P.; Silva, J. C. O.; Siqueira, F. V. C.; Custódio, D. M.

2017-05-01

The physical mechanism of lightning attachment to grounded structures is one of the most important issues in lightning physics research, and it is the basis for the design of the lightning protection systems. Most of what is known about the attachment process comes from leader propagation models that are mostly based on laboratory observations of long electrical discharges or from observations of lightning attachment to tall structures. In this paper we use high-speed videos to analyze the attachment process of downward lightning flashes to an ordinary residential building. For the first time, we present characteristics of the attachment process to common structures that are present in almost every city (in this case, two buildings under 60 m in São Paulo City, Brazil). Parameters like striking distance and connecting leaders speed, largely used in lightning attachment models and in lightning protection standards, are revealed in this work.Plain Language SummarySince the time of Benjamin Franklin, no one has ever recorded high-speed video images of a lightning connection to a common building. It is very difficult to do it. Cameras need to be very close to the structure chosen to be observed, and long observation time is required to register one lightning strike to that particular structure. Models and theories used to determine the zone of protection of a lightning rod have been developed, but they all suffer from the lack of field data. The submitted manuscript provides results from high-speed video observations of lightning attachment to low buildings that are commonly found in almost every populated area around the world. The proximity of the camera and the high frame rate allowed us to see interesting details that will improve the understanding of the attachment process and, consequently, the models and theories used by lightning protection standards. This paper also presents spectacular images and videos of lightning flashes connecting lightning rods that

Doorway states in nuclear reactions as a manifestation of the 'super-radiant' mechanism

International Nuclear Information System (INIS)

Auerbach, N.; Zelevinsky, V.

2007-01-01

A mechanism is considered for generating doorway states and intermediate structure in low-energy nuclear reactions as a result of collectivization of widths of unstable intrinsic states coupled to common decay channels. At the limit of strong continuum coupling, the segregation of broad ('super-radiating') and narrow ('trapped') states occurs revealing the separation of direct and compound processes. We discuss the conditions for the appearance of intermediate structure in this process and doorways related to certain decay channels

Load-adaptive bone remodeling simulations reveal osteoporotic microstructural and mechanical changes in whole human vertebrae.

Science.gov (United States)

Badilatti, Sandro D; Christen, Patrik; Parkinson, Ian; Müller, Ralph

2016-12-08

Osteoporosis is a major medical burden and its impact is expected to increase in our aging society. It is associated with low bone density and microstructural deterioration. Treatments are available, but the critical factor is to define individuals at risk from osteoporotic fractures. Computational simulations investigating not only changes in net bone tissue volume, but also changes in its microstructure where osteoporotic deterioration occur might help to better predict the risk of fractures. In this study, bone remodeling simulations with a mechanical feedback loop were used to predict microstructural changes due to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of a group of seven, mixed sex whole vertebrae, five mechanostat models mimicking different biological alterations associated with osteoporosis were developed, leading to imbalanced bone formation and resorption with a total net loss of bone tissue. A model with reduced bone formation rate and cell sensitivity led to the best match of morphometric indices compared to literature data and was chosen to predict postmenopausal osteoporotic bone loss in the whole group. Thirty years of osteoporotic bone loss were predicted with changes in morphometric indices in agreement with experimental measurements, and only showing major deviations in trabecular number and trabecular separation. In particular, although being optimized to match to the morphometric indices alone, the predicted bone loss revealed realistic changes on the organ level and on biomechanical competence. While the osteoporotic bone was able to maintain the mechanical stability to a great extent, higher fragility towards error loads was found for the osteoporotic bones. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical engineers' handbook, materials and engineering mechanics

CERN Document Server

Kutz, Myer

2015-01-01

Full coverage of materials and mechanical design inengineering Mechanical Engineers' Handbook, Fourth Edition provides aquick guide to specialized areas you may encounter in your work,giving you access to the basics of each and pointing you towardtrusted resources for further reading, if needed. The accessibleinformation inside offers discussions, examples, and analyses ofthe topics covered. This first volume covers materials and mechanical design, givingyou accessible and in-depth access to the most common topics you'llencounter in the discipline: carbon and alloy steels, stainlesssteels, a

Infection due to Mycobacterium bovis in common variable immunodeficiency

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Diana Andrea Herrera-Sánchez

2015-02-01

Full Text Available Common variable immunodeficiency (CVID is an heterogeneous group of disorders characterized by impaired antibody production. It shows a wide spectrum of manifestations including severe and recurrent respiratory infections (Streptococcus pneumoniae, Haemophilus and gastrointestinal (Campylobacter jejuni, rotavirus and Giardia lamblia. Viral infections caused by herpes zoster, cytomegalovirus (CMV and hepatitis C are rare. The opportunistic agents such as CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been reported as isolated cases. This paper reports the case of a 38-year-old female patient, who began six years before with weight loss of 7 kg in six months, fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had intestinal obstruction and abdominal CT showed mesenteric lymph growth. The mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen staining and culture for M. bovis. In the laparotomy postoperative period was complicated with nosocomial pneumonia, requiring mechanical ventilation and tracheostomy. Two years later, she developed right renal abscess that required surgical drainage, once again with a positive culture for Mycobacterium bovis. She was referred to highly specialized hospital and we documented panhypogammaglobulinemia and lymphopenia. Secondary causes of hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID was confirmed, we started IVIG replacement. Four years later she developed mixed cellularity Hodgkin’s lymphoma. Until today she continues with IVIG and chemotherapy. This report of a patient with CVID and Mycobacterium bovis infection, a unusual association, shows the cellular immunity susceptibility in this immunodeficiency, additional to the humoral defect.

Genetic mechanisms and age-related macular degeneration: common variants, rare variants, copy number variations, epigenetics, and mitochondrial genetics

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Liu Melissa M

2012-08-01

Full Text Available Abstract Age-related macular degeneration (AMD is a complex and multifaceted disease involving contributions from both genetic and environmental influences. Previous work exploring the genetic contributions of AMD has implicated numerous genomic regions and a variety of candidate genes as modulators of AMD susceptibility. Nevertheless, much of this work has revolved around single-nucleotide polymorphisms (SNPs, and it is apparent that a significant portion of the heritability of AMD cannot be explained through these mechanisms. In this review, we consider the role of common variants, rare variants, copy number variations, epigenetics, microRNAs, and mitochondrial genetics in AMD. Copy number variations in regulators of complement activation genes (CFHR1 and CFHR3 and glutathione S transferase genes (GSTM1 and GSTT1 have been associated with AMD, and several additional loci have been identified as regions of potential interest but require further evaluation. MicroRNA dysregulation has been linked to the retinal pigment epithelium degeneration in geographic atrophy, ocular neovascularization, and oxidative stress, all of which are hallmarks in the pathogenesis of AMD. Certain mitochondrial DNA haplogroups and SNPs in mitochondrially encoded NADH dehydrogenase genes have also been associated with AMD. The role of these additional mechanisms remains only partly understood, but the importance of their further investigation is clear to elucidate more completely the genetic basis of AMD.

Leaf cDNA-AFLP analysis reveals novel mechanisms for boron-induced alleviation of aluminum-toxicity in Citrus grandis seedlings.

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Wang, Liu-Qing; Yang, Lin-Tong; Guo, Peng; Zhou, Xin-Xing; Ye, Xin; Chen, En-Jun; Chen, Li-Song

2015-10-01

Little information is available on the molecular mechanisms of boron (B)-induced alleviation of aluminum (Al)-toxicity. 'Sour pummelo' (Citrus grandis) seedlings were irrigated for 18 weeks with nutrient solution containing different concentrations of B (2.5 or 20μM H3BO3) and Al (0 or 1.2mM AlCl3·6H2O). B alleviated Al-induced inhibition in plant growth accompanied by lower leaf Al. We used cDNA-AFLP to isolate 127 differentially expressed genes from leaves subjected to B and Al interactions. These genes were related to signal transduction, transport, cell wall modification, carbohydrate and energy metabolism, nucleic acid metabolism, amino acid and protein metabolism, lipid metabolism and stress responses. The ameliorative mechanisms of B on Al-toxicity might be related to: (a) triggering multiple signal transduction pathways; (b) improving the expression levels of genes related to transport; (c) activating genes involved in energy production; and (d) increasing amino acid accumulation and protein degradation. Also, genes involved in nucleic acid metabolism, cell wall modification and stress responses might play a role in B-induced alleviation of Al-toxicity. To conclude, our findings reveal some novel mechanisms on B-induced alleviation of Al-toxicity at the transcriptional level in C. grandis leaves. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcium transport mechanism in molting crayfish revealed by microanalysis

International Nuclear Information System (INIS)

Mizuhira, V.; Ueno, M.

1983-01-01

Crayfish provide a good model in which to study the transport mechanism of Ca ions. During the molting stage, decalcified Ca ions are transferred into the blood and accumulate in the gastrolith epithelium, after which a gastrolith is formed on the surface of the epithelium. The gastrolith is dissolved in the stomach after molting, and the Ca is reabsorbed and redistributed throughout the newly formed exoskeleton. We studied the mechanism of Ca transport by cytochemical precipitation of Ca ions and by electron microanalysis, including X-ray microanalysis (EDX) and electron energy-loss spectroscopy (EELS), with a computer. In EDX analysis, the fine precipitates of K-antimonate in the gastrolith mitochondria clearly defined Ca with antimony; we also observed a large amount of Ca-oxalate in the mitochondria, and Ca-K X-ray pulses were clearly defined. Ca-K X-rays were also detected from fresh freeze-substituted mitochondria. Finally, we succeeded in taking a Ca-L EELS image from the mitochondria of fresh freeze-substituted thin sections. Only a very small amount of Ca was detected from the cell membrane and other organelles. Ca-adenosine triphosphatase (ATPase) and Mg-ATPase activity was also very clearly demonstrated in the mitochondria. These enzymes may play an important role in Ca metabolism

A Novel Method of Mechanical Oxidation of CNT for Polymer Nanocomposite Application: Evaluation of Mechanical, Dynamic Mechanical, and Rheological Properties

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Priyanka Pandey

2014-01-01

Full Text Available A new approach of oxidation of carbon nanotubes has been used to oxidize the CNTs. A comparative aspect of the mechanical oxidation and acid oxidation process has been established. FTIR analysis and titration method have shown the higher feasibility of the mechanical oxidation method to oxidize the CNTs. Comparatively less damage to the CNTs has been observed in case of mechanically oxidized as compared to acid oxidized CNTs. The mechanical properties of the nanocomposites reinforced with the acid oxidized CNT (ACNT and mechanically oxidized CNTs (McCNT were analyzed and relatively higher properties in the nanocomposites reinforced with McCNT were noticed. The less degree of entanglement in the McCNTs was noticed as compared to ACNTs. The dynamic mechanical analysis of the nanocomposites revealed much improved load transfer capability in the McCNT reinforced composites. Further, the rheological properties of the nanocomposites revealed the higher performance of McCNT reinforced composites.

A Common Mechanism Underlying Food Choice and Social Decisions.

Directory of Open Access Journals (Sweden)

Ian Krajbich

2015-10-01

Full Text Available People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

Large-scale analysis by SAGE reveals new mechanisms of v-erbA oncogene action

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Faure Claudine

2007-10-01

Full Text Available Abstract Background: The v-erbA oncogene, carried by the Avian Erythroblastosis Virus, derives from the c-erbAα proto-oncogene that encodes the nuclear receptor for triiodothyronine (T3R. v-ErbA transforms erythroid progenitors in vitro by blocking their differentiation, supposedly by interference with T3R and RAR (Retinoic Acid Receptor. However, v-ErbA target genes involved in its transforming activity still remain to be identified. Results: By using Serial Analysis of Gene Expression (SAGE, we identified 110 genes deregulated by v-ErbA and potentially implicated in the transformation process. Bioinformatic analysis of promoter sequence and transcriptional assays point out a potential role of c-Myb in the v-ErbA effect. Furthermore, grouping of newly identified target genes by function revealed both expected (chromatin/transcription and unexpected (protein metabolism functions potentially deregulated by v-ErbA. We then focused our study on 15 of the new v-ErbA target genes and demonstrated by real time PCR that in majority their expression was activated neither by T3, nor RA, nor during differentiation. This was unexpected based upon the previously known role of v-ErbA. Conclusion: This paper suggests the involvement of a wealth of new unanticipated mechanisms of v-ErbA action.

Bacterial 16S rRNA gene analysis revealed that bacteria related to Arcobacter spp. constitute an abundant and common component of the oyster microbiota (Tiostrea chilensis).

Science.gov (United States)

Romero, J; García-Varela, M; Laclette, J P; Espejo, R T

2002-11-01

To explore the bacterial microbiota in Chilean oyster (Tiostrea chilensis), a molecular approach that permits detection of different bacteria, independently of their capacity to grow in culture media, was used. Bacterial diversity was assessed by analysis of both the 16S rDNA and the 16S-23S intergenic region, obtained by PCR amplifications of DNA extracted from depurated oysters. RFLP of the PCR amplified 16S rDNA showed a prevailing pattern in most of the individuals analyzed, indicating that a few bacterial species were relatively abundant and common in oysters. Cloning and sequencing of the 16S rDNA with the prevailing RFLP pattern indicated that this rRNA was most closely related to Arcobacter spp. However, analysis by the size of the amplified 16S-23S rRNA intergenic regions revealed not Arcobacter spp. but Staphylococcus spp. related bacteria as a major and common component in oyster. These different results may be caused by the absence of target for one of the primers employed for amplification of the intergenic region. Neither of the two bacteria species found in large abundance was recovered after culturing under aerobic, anaerobic, or microaerophilic conditions. This result, however, is expected because the number of bacteria recovered after cultivation was less than 0.01% of the total. All together, these observations suggest that Arcobacter-related strains are probably abundant and common in the Chilean oyster bacterial microbiota.

Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

Science.gov (United States)

Iriki, Atsushi; Isoda, Masaki

2015-01-01

Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

Genetics of infectious diseases: hidden etiologies and common pathways.

Science.gov (United States)

Orlova, Marianna; Di Pietrantonio, Tania; Schurr, Erwin

2011-09-01

Since the completion of the human genome sequence, the study of common genetic polymorphisms in complex human diseases has become a main activity of human genetics. Employing genome-wide association studies, hundreds of modest genetic risk factors have been identified. In infectious diseases the identification of common risk factors has been varied and as in other common diseases it seems likely that important genetic risk factors remain to be discovered. Nevertheless, the identification of disease-specific genetic risk factors revealed an unexpected overlap in susceptibility genes of diverse inflammatory and infectious diseases. Analysis of the multi-disease susceptibility genes has allowed the definition of shared key pathways of inflammatory dysregulation and suggested unexpected infectious etiologies for other "non-infectious" common diseases.

Comparison of closely related, uncultivated Coxiella tick endosymbiont population genomes reveals clues about the mechanisms of symbiosis.

Science.gov (United States)

Tsementzi, Despina; Castro Gordillo, Juan; Mahagna, Mustafa; Gottlieb, Yuval; Konstantinidis, Konstantinos T

2018-05-01

Understanding the symbiotic interaction between Coxiella-like endosymbionts (CLE) and their tick hosts is challenging due to lack of isolates and difficulties in tick functional assays. Here we sequenced the metagenome of a CLE population from wild Rhipicephalus sanguineus ticks (CRs) and compared it to the previously published genome of its close relative, CLE of R. turanicus (CRt). The tick hosts are closely related sympatric species, and their two endosymbiont genomes are highly similar with only minor differences in gene content. Both genomes encode numerous pseudogenes, consistent with an ongoing genome reduction process. In silico flux balance metabolic analysis (FBA) revealed the excess production of L-proline for both genomes, indicating a possible proline transport from Coxiella to the tick. Additionally, both CR genomes encode multiple copies of the proline/betaine transporter, proP gene. Modelling additional Coxiellaceae members including other tick CLE, did not identify proline as an excreted metabolite. Although both CRs and CRt genomes encode intact B vitamin synthesis pathway genes, which are presumed to underlay the mechanism of CLE-tick symbiosis, the FBA analysis indicated no changes for their products. Therefore, this study provides new testable hypotheses for the symbiosis mechanism and a better understanding of CLE genome evolution and diversity. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Exploring mechanisms of compaction in salt-marsh sediments using Common Era relative sea-level reconstructions

Science.gov (United States)

Brain, Matthew J.; Kemp, Andrew C.; Hawkes, Andrea D.; Engelhart, Simon E.; Vane, Christopher H.; Cahill, Niamh; Hill, Troy D.; Donnelly, Jeffrey P.; Horton, Benjamin P.

2017-07-01

Salt-marsh sediments provide precise and near-continuous reconstructions of Common Era relative sea level (RSL). However, organic and low-density salt-marsh sediments are prone to compaction processes that cause post-depositional distortion of the stratigraphic column used to reconstruct RSL. We compared two RSL reconstructions from East River Marsh (Connecticut, USA) to assess the contribution of mechanical compression and biodegradation to compaction of salt-marsh sediments and their subsequent influence on RSL reconstructions. The first, existing reconstruction ('trench') was produced from a continuous sequence of basal salt-marsh sediment and is unaffected by compaction. The second, new reconstruction is from a compaction-susceptible core taken at the same location. We highlight that sediment compaction is the only feasible mechanism for explaining the observed differences in RSL reconstructed from the trench and core. Both reconstructions display long-term RSL rise of ∼1 mm/yr, followed by a ∼19th Century acceleration to ∼3 mm/yr. A statistically-significant difference between the records at ∼1100 to 1800 CE could not be explained by a compression-only geotechnical model. We suggest that the warmer and drier conditions of the Medieval Climate Anomaly (MCA) resulted in an increase in sediment compressibility during this time period. We adapted the geotechnical model by reducing the compressive strength of MCA sediments to simulate this softening of sediments. 'Decompaction' of the core reconstruction with this modified model accounted for the difference between the two RSL reconstructions. Our results demonstrate that compression-only geotechnical models may be inadequate for estimating compaction and post-depositional lowering of susceptible organic salt-marsh sediments in some settings. This has important implications for our understanding of the drivers of sea-level change. Further, our results suggest that future climate changes may make salt

Size-dependent physicochemical and mechanical interactions in battery paste anodes of Si-microwires revealed by Fast-Fourier-Transform Impedance Spectroscopy

Science.gov (United States)

Hansen, Sandra; Quiroga-González, Enrique; Carstensen, Jürgen; Adelung, Rainer; Föll, Helmut

2017-05-01

Perfectly aligned silicon microwire arrays show exceptionally high cycling stability with record setting (high) areal capacities of 4.25 mAh cm-2. Those wires have a special, modified length and thickness in order to perform this good. Geometry and sizes are the most important parameters of an anode to obtain batteries with high cycling stability without irreversible losses. The wires are prepared with a unique etching fabrication method, which allows to fabricate wires of very precise sizes. In order to investigate how good randomly oriented silicon wires perform in contrast to the perfect order of the array, the wires are embedded in a paste. This study reveals the fundamental correlation between geometry, mechanics and charge transfer kinetics of silicon electrodes. Using a suitable RC equivalent circuit allows to evaluate data from cyclic voltammetry and simultaneous FFT-Impedance Spectroscopy (FFT-IS), yielding in time-resolved resistances, time constants, and their direct correlation to the phase transformations. The change of the resistances during lithiation and delithiation correlates to kinetics and charge transfer mechanisms. This study demonstrates how the mechanical and physiochemical interactions at the silicon/paste interface inside the paste electrodes lead to void formation around silicon and with it to material loss and capacity fading.

Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

Science.gov (United States)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

Seahorse Brood Pouch Transcriptome Reveals Common Genes Associated with Vertebrate Pregnancy.

Science.gov (United States)

Whittington, Camilla M; Griffith, Oliver W; Qi, Weihong; Thompson, Michael B; Wilson, Anthony B

2015-12-01

Viviparity (live birth) has evolved more than 150 times in vertebrates, and represents an excellent model system for studying the evolution of complex traits. There are at least 23 independent origins of viviparity in fishes, with syngnathid fishes (seahorses and pipefish) unique in exhibiting male pregnancy. Male seahorses and pipefish have evolved specialized brooding pouches that provide protection, gas exchange, osmoregulation, and limited nutrient provisioning to developing embryos. Pouch structures differ widely across the Syngnathidae, offering an ideal opportunity to study the evolution of reproductive complexity. However, the physiological and genetic changes facilitating male pregnancy are largely unknown. We used transcriptome profiling to examine pouch gene expression at successive gestational stages in a syngnathid with the most complex brood pouch morphology, the seahorse Hippocampus abdominalis. Using a unique time-calibrated RNA-seq data set including brood pouch at key stages of embryonic development, we identified transcriptional changes associated with brood pouch remodeling, nutrient and waste transport, gas exchange, osmoregulation, and immunological protection of developing embryos at conception, development and parturition. Key seahorse transcripts share homology with genes of reproductive function in pregnant mammals, reptiles, and other live-bearing fish, suggesting a common toolkit of genes regulating pregnancy in divergent evolutionary lineages. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Separating grain boundary migration mechanisms in molecular dynamics simulations

International Nuclear Information System (INIS)

Ulomek, Felix; Mohles, Volker

2016-01-01

In molecular dynamics (MD) simulations of grain boundary (GB) migration it is quite common to find a temperature dependence of GB mobility that deviates strongly from an Arrhenius-type dependence. This usually indicates that more than one mechanism is actually active. With the goal to separate different GB migration mechanisms we investigate a Σ7 <111> 38.2° GB by MD using an EAM potential for aluminium. To drive the GB with a well-known and adjustable force, the energy conserving orientational driving force (ECO DF) is used that had been introduced recently. The magnitude of the DF and the temperature are varied. This yielded a high and a low temperature range for the GB velocity, with a transition temperature that depends on the magnitude of the DF. A method is introduced which allows both a visual and a statistical characterization of GB motion on a per atom basis. These analyses reveal that two mechanisms are active in this GB, a shuffling mechanism and its initiation. These mechanisms operate in a sequential, coupled manner. Based on this, a simple model is introduced that describes all simulated GB velocities (and hence the mobility) very well, including the transition between the dominating mechanisms.

Martensite and bainite in steels: transformation mechanism and mechanical properties

International Nuclear Information System (INIS)

Bhadeshia, H.K.D.H.

1997-01-01

Many essential properties of iron alloys depend on what actually happens when one allotropic form gives way to another, i.e. on the mechanism of phase change. The dependence of the mechanical properties on the atomic mechanism by which bainite and martensite grow is the focus of this paper. The discussion is illustrated in the context of some common engineering design parameters, and with a brief example of the inverse problem in which the mechanism may be a function of the mechanical properties. (orig.)

Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

Science.gov (United States)

Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

Signature gene expression reveals novel clues to the molecular mechanisms of dimorphic transition in Penicillium marneffei.

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Ence Yang

2014-10-01

Full Text Available Systemic dimorphic fungi cause more than one million new infections each year, ranking them among the significant public health challenges currently encountered. Penicillium marneffei is a systemic dimorphic fungus endemic to Southeast Asia. The temperature-dependent dimorphic phase transition between mycelium and yeast is considered crucial for the pathogenicity and transmission of P. marneffei, but the underlying mechanisms are still poorly understood. Here, we re-sequenced P. marneffei strain PM1 using multiple sequencing platforms and assembled the genome using hybrid genome assembly. We determined gene expression levels using RNA sequencing at the mycelial and yeast phases of P. marneffei, as well as during phase transition. We classified 2,718 genes with variable expression across conditions into 14 distinct groups, each marked by a signature expression pattern implicated at a certain stage in the dimorphic life cycle. Genes with the same expression patterns tend to be clustered together on the genome, suggesting orchestrated regulations of the transcriptional activities of neighboring genes. Using qRT-PCR, we validated expression levels of all genes in one of clusters highly expressed during the yeast-to-mycelium transition. These included madsA, a gene encoding MADS-box transcription factor whose gene family is exclusively expanded in P. marneffei. Over-expression of madsA drove P. marneffei to undergo mycelial growth at 37°C, a condition that restricts the wild-type in the yeast phase. Furthermore, analyses of signature expression patterns suggested diverse roles of secreted proteins at different developmental stages and the potential importance of non-coding RNAs in mycelium-to-yeast transition. We also showed that RNA structural transition in response to temperature changes may be related to the control of thermal dimorphism. Together, our findings have revealed multiple molecular mechanisms that may underlie the dimorphic transition

Dual mechanism of chromatin remodeling in the common shrew sex trivalent (XY 1Y 2

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Sergey N. Matveevsky

2017-11-01

Full Text Available Here we focus on the XY1Y2 condition in male common shrew Sorex araneus Linnaeus, 1758, applying electron microscopy and immunocytochemistry for a comprehensive analysis of structure, synapsis and behaviour of the sex trivalent in pachytene spermatocytes. The pachytene sex trivalent consists of three distinct parts: short and long synaptic SC fragments (between the X and Y1 and between the X and Y2, respectively and a long asynaptic region of the X in-between. Chromatin inactivation was revealed in the XY1 synaptic region, the asynaptic region of the X and a very small asynaptic part of the Y2. This inactive part of the sex trivalent, that we named the ‘head’, forms a typical sex body and is located at the periphery of the meiotic nucleus at mid pachytene. The second part or ‘tail’, a long region of synapsis between the X and Y2 chromosomes, is directed from the periphery into the nucleus. Based on the distribution patterns of four proteins involved in chromatin inactivation, we propose a model of meiotic silencing in shrew sex chromosomes. Thus, we conclude that pachytene sex chromosomes are structurally and functionally two different chromatin domains with specific nuclear topology: the peripheral inactivated ‘true’ sex chromosome regions (part of the X and the Y1 and more centrally located transcriptionally active autosomal segments (part of the X and the Y2.

Crowding in Visual Working Memory Reveals Its Spatial Resolution and the Nature of Its Representations.

Science.gov (United States)

Tamber-Rosenau, Benjamin J; Fintzi, Anat R; Marois, René

2015-09-01

Spatial resolution fundamentally limits any image representation. Although this limit has been extensively investigated for perceptual representations by assessing how neighboring flankers degrade the perception of a peripheral target with visual crowding, the corresponding limit for representations held in visual working memory (VWM) is unknown. In the present study, we evoked crowding in VWM and directly compared resolution in VWM and perception. Remarkably, the spatial resolution of VWM proved to be no worse than that of perception. However, mixture modeling of errors caused by crowding revealed the qualitatively distinct nature of these representations. Perceptual crowding errors arose from both increased imprecision in target representations and substitution of flankers for targets. By contrast, VWM crowding errors arose exclusively from substitutions, which suggests that VWM transforms analog perceptual representations into discrete items. Thus, although perception and VWM share a common resolution limit, exceeding this limit reveals distinct mechanisms for perceiving images and holding them in mind. © The Author(s) 2015.

Categorization in Infancy: Labeling Induces a Persisting Focus on Commonalities

Science.gov (United States)

Althaus, Nadja; Plunkett, Kim

2016-01-01

Recent studies with infants and adults demonstrate a facilitative role of labels in object categorization. A common interpretation is that labels highlight commonalities between objects. However, direct evidence for such a mechanism is lacking. Using a novel object category with spatially separate features that are either of low or high…

Narrow-front loop migration in a population of the common cuckoo Cuculus canorus, as revealed by satellite telemetry.

Directory of Open Access Journals (Sweden)

Mikkel Willemoes

Full Text Available Narrow migration corridors known in diurnal, social migrants such as raptors, storks and geese are thought to be caused by topographical leading line effects in combination with learning detailed routes across generations. Here, we document narrow-front migration in a nocturnal, solitary migrant, the common cuckoo Cuculus canorus, using satellite telemetry. We tracked the migration of adult cuckoos from the breeding grounds in southern Scandinavia (n = 8, to wintering sites in south-western Central Africa (n = 6 and back to the breeding grounds (n = 3. Migration patterns were very complex; in addition to the breeding and wintering sites, six different stopover sites were identified during the 16,000 km annual route that formed a large-scale clockwise loop. Despite this complexity, individuals showed surprisingly similar migration patterns, with very little variation between routes. We compared observed tracks with simulated routes based on vector orientation (with and without effects of barriers on orientation and survival. Observed distances between routes were often significantly smaller than expected if the routes were established on the basis of an innate vector orientation programme. Average distance between individuals in eastern Sahel after having migrated more than 5,000 km for example, was merely 164 km. This implies that more sophisticated inherent guiding mechanisms, possibly involving elements of intermediate goal area navigation or more elaborate external cues, are necessary to explain the complex narrow-front migration pattern observed for the cuckoos in this study.

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

Science.gov (United States)

Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

2016-04-05

Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases.

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Bettencourt, Conceição; Hensman-Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas-Gómez, Petra; García-Velázquez, Lizbeth Esmeralda; Alonso-Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J; Jones, Lesley

2016-06-01

The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome-wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single-nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10(-5) ). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10(-5) ) and all SCAs (p = 2.22 × 10(-4) ) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10(-5) ), all in the same direction as in the HD GWAS. We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983-990. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Patient-ventilator trigger dys-synchrony: a common phenomenon with important implications

OpenAIRE

MacIntyre, Neil

2013-01-01

Patient-ventilator trigger dys-synchronies are common with the use of assisted forms of mechanical ventilatory support, including non-invasive mechanical ventilatory support (NIV). Future system designs need to address this in order to improve the effectiveness of NIV.

Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs.

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Dimitar V Pachov

2015-07-01

Full Text Available Proteins perform their function or interact with partners by exchanging between conformational substates on a wide range of spatiotemporal scales. Structurally characterizing these exchanges is challenging, both experimentally and computationally. Large, diffusional motions are often on timescales that are difficult to access with molecular dynamics simulations, especially for large proteins and their complexes. The low frequency modes of normal mode analysis (NMA report on molecular fluctuations associated with biological activity. However, NMA is limited to a second order expansion about a minimum of the potential energy function, which limits opportunities to observe diffusional motions. By contrast, kino-geometric conformational sampling (KGS permits large perturbations while maintaining the exact geometry of explicit conformational constraints, such as hydrogen bonds. Here, we extend KGS and show that a conformational ensemble of the α subunit Gαs of heterotrimeric stimulatory protein Gs exhibits structural features implicated in its activation pathway. Activation of protein Gs by G protein-coupled receptors (GPCRs is associated with GDP release and large conformational changes of its α-helical domain. Our method reveals a coupled α-helical domain opening motion while, simultaneously, Gαs helix α5 samples an activated conformation. These motions are moderated in the activated state. The motion centers on a dynamic hub near the nucleotide-binding site of Gαs, and radiates to helix α4. We find that comparative NMA-based ensembles underestimate the amplitudes of the motion. Additionally, the ensembles fall short in predicting the accepted direction of the full activation pathway. Taken together, our findings suggest that nullspace sampling with explicit, holonomic constraints yields ensembles that illuminate molecular mechanisms involved in GDP release and protein Gs activation, and further establish conformational coupling between key

The association between type of spine fracture and the mechanism of trauma: A useful tool for identifying mechanism of trauma on legal medicine field.

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Aghakhani, Kamran; Kordrostami, Roya; Memarian, Azadeh; Asl, Nahid Dadashzadeh; Zavareh, Fatemeh Noorian

2018-05-01

Determining the association between mechanism of trauma, and the type of spine column fracture is a useful approach for exactly describing spine injury on forensic medicine field. We aimed to determine mechanism of trauma based on distribution of the transition of spinal column fractures. This cross-sectional survey was performed on 117 consecutive patients with the history of spinal trauma who were admitted to emergency ward of Rasoul-e-Akram Hospital in Tehran, Iran from April 2015 to March 2016. The baseline characteristics were collected by reviewing the hospital recorded files. With respect to mechanism of fracture, 63.2% of fractures were caused by falling, 30.8% by collisions with motor vehicles, and others caused by the violence. Regarding site of fracture, lumbosacral was affected in 47.9%, thoracic in 29.9%, and cervical in 13.7%. Regarding type of fracture, burst fracture was the most common type (71.8%) followed by compressive fracture (14.5%). The site of fracture was specifically associated with the mechanism of injury; the most common injuries induced by falling from height were found in lumbosacral and cervical sites, and the most frequent injuries by traffic accidents were found in thoracic site; also the injuries following violence were observed more in lumbar vertebrae. The burst fractures were more revealed in the patients affected by falling from height and by traffic accidents, and both burst and compressive fractures were more observed with the same result in the patients injured with violence (p = 0.003). The type of spine fracture due to trauma is closely associated with the mechanism of trauma that can be helpful in legal medicine to identify the mechanism of trauma in affected patients. Copyright © 2018. Published by Elsevier Ltd.

Institutional property rights structure, common pool resource (CPR), tragedy of the urban commons: A Review

Science.gov (United States)

Ling, G.; Ho, C. S.; Ali, H. M.

2014-02-01

There have been a plethora of researches on the significance of public open space (POS) in contributing to societies' sustainability. However, by virtue of identified maladaptive policy-based-property rights structure, such a shared good becomes vulnerable to tragedy of the urban commons (overexploitation) that subsequently leads to burgeoning number of mismanaged POS e.g., degraded and unkempt urban public spaces. By scrutinising the literatures within property rights domain and commons resources, an objective is highlighted in this paper which is to insightfully discourse institutional property rights structure pertaining to the mechanism, roles and interrelationship between property-rights regimes, bundle of property rights and resource domains; types of goods on how they act upon and tie in the POS with the social quandary. In summary, urban POS tragedy can potentially be triggered by the institutional structure especially if the ownership is left under open-access resource regime and ill-defined property rights which both successively constitute the natures of Common Pool Resource (CPR) within the commons, POS. Therefore, this paper sparks an idea to policy makers that property rights structure is a determinant in sustainably governing the POS in which adaptive assignment of property regimes and property rights are impelled.

Institutional property rights structure, common pool resource (CPR), tragedy of the urban commons: A Review

International Nuclear Information System (INIS)

Ling, G; Ho, C S; Ali, H M

2014-01-01

There have been a plethora of researches on the significance of public open space (POS) in contributing to societies' sustainability. However, by virtue of identified maladaptive policy-based-property rights structure, such a shared good becomes vulnerable to tragedy of the urban commons (overexploitation) that subsequently leads to burgeoning number of mismanaged POS e.g., degraded and unkempt urban public spaces. By scrutinising the literatures within property rights domain and commons resources, an objective is highlighted in this paper which is to insightfully discourse institutional property rights structure pertaining to the mechanism, roles and interrelationship between property-rights regimes, bundle of property rights and resource domains; types of goods on how they act upon and tie in the POS with the social quandary. In summary, urban POS tragedy can potentially be triggered by the institutional structure especially if the ownership is left under open-access resource regime and ill-defined property rights which both successively constitute the natures of Common Pool Resource (CPR) within the commons, POS. Therefore, this paper sparks an idea to policy makers that property rights structure is a determinant in sustainably governing the POS in which adaptive assignment of property regimes and property rights are impelled

Unique and Common Mechanisms of Change across Cognitive and Dynamic Psychotherapies

Science.gov (United States)

Gibbons, Mary Beth Connolly; Crits-Christoph, Paul; Barber, Jacques P.; Stirman, Shannon Wiltsey; Gallop, Robert; Goldstein, Lizabeth A.; Temes, Christina M.; Ring-Kurtz, Sarah

2009-01-01

The goal of this article was to examine theoretically important mechanisms of change in psychotherapy outcome across different types of treatment. Specifically, the role of gains in self-understanding, acquisition of compensatory skills, and improvements in views of the self were examined. A pooled study database collected at the University of…

mRNA-Seq Reveals Novel Molecular Mechanisms and a Robust Fingerprint in Graves' Disease

Science.gov (United States)

Sachidanandam, Ravi; Morshed, Syed; Latif, Rauf; Shi, Ruijin; Davies, Terry F.

2014-01-01

Context: The immune response in autoimmune thyroid disease has been shown to occur primarily within the thyroid gland in which the most abundant antigens can be found. A variety of capture molecules are known to be expressed by thyroid epithelial cells and serve to attract and help retain an intrathyroidal immune infiltrate. Objective: To explore the entire repertoire of expressed genes in human thyroid tissue, we have deep sequenced the transcriptome (referred to as mRNA-Seq). Design and Patients: We applied mRNA-Seq to thyroid tissue from nine patients with Graves' disease subjected to total thyroidectomy and compared the data with 12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing data by taking the median of the coverage across the length of the gene. The expression levels were quantile normalized and a gene signature was derived from these. Results: On comparison of expression levels in tissues derived from Graves' patients and controls, there was clear evidence for overexpression of the antigen presentation pathway consisting of HLA and associated genes. We also found a robust disease signature and discovered active innate and adaptive immune signaling networks. Conclusions: These data reveal an active immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development. PMID:24971664

Floral reversion mechanism in longan (Dimocarpus longan Lour.) revealed by proteomic and anatomic analyses.

Science.gov (United States)

You, Xiangrong; Wang, Lingxia; Liang, Wenyu; Gai, Yonghong; Wang, Xiaoyan; Chen, Wei

2012-02-02

Two-dimensional gel electrophoresis (2-DE) was used to analyze the proteins related to floral reversion in Dimocarpus longan Lour. Proteins were extracted from buds undergoing the normal process of flowering and from those undergoing floral reversion in three developing stages in D. longan. Differentially expressed proteins were identified from the gels after 2-DE analysis, which were confirmed using matrix-assisted laser desorption/ionization-time of flying-mass spectroscopy and protein database search. A total of 39 proteins, including 18 up-regulated and 21 down-regulated proteins, were classified into different categories, such as energy and substance metabolism, protein translation, secondary metabolism, phytohormone, cytoskeleton structure, regulation, and stress tolerance. Among these, the largest functional class was associated with primary metabolism. Down-regulated proteins were involved in photosynthesis, transcription, and translation, whereas up-regulated proteins were involved in respiration. Decreased flavonoid synthesis and up-regulated GA20ox might be involved in the floral reversion process. Up-regulated 14-3-3 proteins played a role in the regulation of floral reversion in D. longan by responding to abiotic stress. Observations via transmission electron microscopy revealed the ultrastructure changes in shedding buds undergoing floral reversion. Overall, the results provided insights into the molecular basis for the floral reversion mechanism in D. longan. Copyright © 2011 Elsevier B.V. All rights reserved.

Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

International Nuclear Information System (INIS)

Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

2014-01-01

Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

Commonalities and distinctions among mechanisms of addiction to alcohol and other drugs

Science.gov (United States)

Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.

2015-01-01

Alcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. In this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in pre-clinical studies using rodent models of drug self-administration. While there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. For alcohol, versus other drugs of abuse, we discuss and compare advances in: 1) neurocircuitry important for the different stages of drug dependence; 2) transcriptomics and genetical genomics; and 3) enduring effects. We note in particular the contributions of behavioral genetics and animal models: discussions of progress specifically relevant to treatment development can be found in the accompanying review (Karoly et al, this issue). PMID:26431116

Mechanical behaviour of Zn–Al–Cu–Mg alloys: Deformation mechanisms of as-cast microstructures

Energy Technology Data Exchange (ETDEWEB)

Wu, Zhicheng; Sandlöbes, Stefanie; Wu, Liang; Hu, Weiping; Gottstein, Günter; Korte-Kerzel, Sandra, E-mail: Korte-Kerzel@imm.rwth-aachen.de

2016-01-10

We study the effects of dilute Mg addition on the microstructure formation and mechanical properties of a ZnAl4Cu1 alloy. On the basis of the composition of the commercial alloy Z410 (4 wt% Al, 1 wt% Cu, and 0.04 wt% Mg), three laboratory alloys with different Mg contents (0.04 wt%, 0.21 wt% and 0.31 wt%) are characterised in terms of their mechanical properties and microstructures using ex-situ and in-situ tensile tests in conjunction with scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). Increasing Mg content causes the precipitation of Mg{sub 2}Zn{sub 11} phase precipitates and refined lamellar spacings in the eutectoid phase. The alloy with a medium Mg content (0.21 wt%) exhibits the highest yield strength both at room temperature and at elevated temperatures. Further, we show that dilute Mg alloying causes an improvement of the ductility of ZnAl4Cu1 base-alloys, especially at elevated temperatures. In addition, the alloys reveal two distinct deformation regimes distinguishable close to room temperature and at commonly employed strain rates, with work hardening and brittle fracture exhibited at room temperature and/or elevated strain rate (5×10{sup −4} s{sup −1}), and work softening and ductile fracture at elevated temperature and/or low strain rate (6×10{sup −6} s{sup −1}). The deformation mechanisms and fracture behaviour in both regimes are investigated and the underlying physical mechanisms of the observed phenomena are discussed.

Mechanical behaviour of Zn–Al–Cu–Mg alloys: Deformation mechanisms of as-cast microstructures

International Nuclear Information System (INIS)

Wu, Zhicheng; Sandlöbes, Stefanie; Wu, Liang; Hu, Weiping; Gottstein, Günter; Korte-Kerzel, Sandra

2016-01-01

We study the effects of dilute Mg addition on the microstructure formation and mechanical properties of a ZnAl4Cu1 alloy. On the basis of the composition of the commercial alloy Z410 (4 wt% Al, 1 wt% Cu, and 0.04 wt% Mg), three laboratory alloys with different Mg contents (0.04 wt%, 0.21 wt% and 0.31 wt%) are characterised in terms of their mechanical properties and microstructures using ex-situ and in-situ tensile tests in conjunction with scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). Increasing Mg content causes the precipitation of Mg_2Zn_1_1 phase precipitates and refined lamellar spacings in the eutectoid phase. The alloy with a medium Mg content (0.21 wt%) exhibits the highest yield strength both at room temperature and at elevated temperatures. Further, we show that dilute Mg alloying causes an improvement of the ductility of ZnAl4Cu1 base-alloys, especially at elevated temperatures. In addition, the alloys reveal two distinct deformation regimes distinguishable close to room temperature and at commonly employed strain rates, with work hardening and brittle fracture exhibited at room temperature and/or elevated strain rate (5×10"−"4 s"−"1), and work softening and ductile fracture at elevated temperature and/or low strain rate (6×10"−"6 s"−"1). The deformation mechanisms and fracture behaviour in both regimes are investigated and the underlying physical mechanisms of the observed phenomena are discussed.

Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

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Nichole M Miller

2015-08-01

Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

'Big bang' of B-cell development revealed.

Science.gov (United States)

Murre, Cornelis

2018-01-15

Earlier studies have identified transcription factors that specify B-cell fate, but the underlying mechanisms remain to be revealed. Two new studies by Miyai and colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of Genes & Development provide new and unprecedented insights into the genetic and epigenetic mechanisms that establish B-cell identity. © 2018 Murre; Published by Cold Spring Harbor Laboratory Press.

Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction.

Science.gov (United States)

Budiyono, Agung; Rohrlich, Daniel

2017-11-03

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an "ontic extension" defines a nonseparable (global) random variable that generates physical correlations, and an "epistemic restriction" constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck's constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.

Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

Science.gov (United States)

Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

2016-07-01

Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

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Huynh Truc

2007-12-01

Full Text Available Abstract Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18 that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

Science.gov (United States)

Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

2015-01-01

The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target.

Common marmoset embryonic stem cell can differentiate into cardiomyocytes

International Nuclear Information System (INIS)

Chen Hao; Hattori, Fumiyuki; Murata, Mitsushige; Li Weizhen; Yuasa, Shinsuke; Onizuka, Takeshi; Shimoji, Kenichiro; Ohno, Yohei; Sasaki, Erika; Kimura, Kensuke; Hakuno, Daihiko

2008-01-01

Common marmoset monkeys have recently attracted much attention as a primate research model, and are preferred to rhesus and cynomolgus monkeys due to their small bodies, easy handling and efficient breeding. We recently reported the establishment of common marmoset embryonic stem cell (CMESC) lines that could differentiate into three germ layers. Here, we report that our CMESC can also differentiate into cardiomyocytes and investigated their characteristics. After induction, FOG-2 was expressed, followed by GATA4 and Tbx20, then Nkx2.5 and Tbx5. Spontaneous beating could be detected at days 12-15. Immunofluorescent staining and ultrastructural analyses revealed that they possessed characteristics typical of functional cardiomyocytes. They showed sinus node-like action potentials, and the beating rate was augmented by isoproterenol stimulation. The BrdU incorporation assay revealed that CMESC-derived cardiomyocytes retained a high proliferative potential for up to 24 weeks. We believe that CMESC-derived cardiomyocytes will advance preclinical studies in cardiovascular regenerative medicine

The dual impact of ecology and management on social incentives in marine common-pool resource systems.

Science.gov (United States)

Klein, E S; Barbier, M R; Watson, J R

2017-08-01

Understanding how and when cooperative human behaviour forms in common-pool resource systems is critical to illuminating social-ecological systems and designing governance institutions that promote sustainable resource use. Before assessing the full complexity of social dynamics, it is essential to understand, concretely and mechanistically, how resource dynamics and human actions interact to create incentives and pay-offs for social behaviours. Here, we investigated how such incentives for information sharing are affected by spatial dynamics and management in a common-pool resource system. Using interviews with fishermen to inform an agent-based model, we reveal generic mechanisms through which, for a given ecological setting characterized by the spatial dynamics of the resource, the two 'human factors' of information sharing and management may heterogeneously impact various members of a group for whom theory would otherwise predict the same strategy. When users can deplete the resource, these interactions are further affected by the management approach. Finally, we discuss the implications of alternative motivations, such as equity among fishermen and consistency of the fleet's output. Our results indicate that resource spatial dynamics, form of management and level of depletion can interact to alter the sociality of people in common-pool resource systems, providing necessary insight for future study of strategic decision processes.

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

Science.gov (United States)

Thybert, David; Roller, Maša; Navarro, Fábio C.P.; Fiddes, Ian; Streeter, Ian; Feig, Christine; Martin-Galvez, David; Kolmogorov, Mikhail; Janoušek, Václav; Akanni, Wasiu; Aken, Bronwen; Aldridge, Sarah; Chakrapani, Varshith; Chow, William; Clarke, Laura; Cummins, Carla; Doran, Anthony; Dunn, Matthew; Goodstadt, Leo; Howe, Kerstin; Howell, Matthew; Josselin, Ambre-Aurore; Karn, Robert C.; Laukaitis, Christina M.; Jingtao, Lilue; Martin, Fergal; Muffato, Matthieu; Nachtweide, Stefanie; Quail, Michael A.; Sisu, Cristina; Stanke, Mario; Stefflova, Klara; Van Oosterhout, Cock; Veyrunes, Frederic; Ward, Ben; Yang, Fengtang; Yazdanifar, Golbahar; Zadissa, Amonida; Adams, David J.; Brazma, Alvis; Gerstein, Mark; Paten, Benedict; Pham, Son; Keane, Thomas M.; Odom, Duncan T.; Flicek, Paul

2018-01-01

Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology. PMID:29563166

Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

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Matthew S Barnabei

Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

Telomeres and viruses: common themes of genome maintenance

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Deng, Zhong; Wang, Zhuo; Lieberman, Paul M.

2012-01-01

Genome maintenance mechanisms actively suppress genetic instability associated with cancer and aging. Some viruses provoke genetic instability by subverting the host’s control of genome maintenance. Viruses have their own specialized strategies for genome maintenance, which can mimic and modify host cell processes. Here, we review some of the common features of genome maintenance utilized by viruses and host chromosomes, with a particular focus on terminal repeat (TR) elements. The TRs of cellular chromosomes, better known as telomeres, have well-established roles in cellular chromosome stability. Cellular telomeres are themselves maintained by viral-like mechanisms, including self-propagation by reverse transcription, recombination, and retrotransposition. Viral TR elements, like cellular telomeres, are essential for viral genome stability and propagation. We review the structure and function of viral repeat elements and discuss how they may share telomere-like structures and genome protection functions. We consider how viral infections modulate telomere regulatory factors for viral repurposing and can alter normal host telomere structure and chromosome stability. Understanding the common strategies of viral and cellular genome maintenance may provide new insights into viral–host interactions and the mechanisms driving genetic instability in cancer. PMID:23293769

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

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Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

Systems Study on the Antirheumatic Mechanism of Tibetan Medicated-Bath Therapy Using Wuwei-Ganlu-Yaoyu-Keli

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Tianhong Wang

2017-01-01

Full Text Available In clinical practice at Tibetan area of China, Traditional Tibetan Medicine formula Wuwei-Ganlu-Yaoyu-Keli (WGYK is commonly added in warm water of bath therapy to treat rheumatoid arthritis (RA. However, its mechanism of action is not well interpreted yet. In this paper, we first verify WGYK’s anti-RA effect by an animal experiment. Then, based on gene expression data from microarray experiments, we apply approaches of network pharmacology to further reveal the mechanism of action for WGYK to treat RA by analyzing protein-protein interactions and pathways. This study may facilitate our understanding of anti-RA effect of WGYK from perspective of network pharmacology.

Epidemiological study on the penicillin resistance of clinical Streptococcus pneumoniae isolates identified as the common sequence types.

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Gao, Wei; Shi, Wei; Chen, Chang-hui; Wen, De-nian; Tian, Jin; Yao, Kai-hu

2016-10-20

There were some limitation in the current interpretation about the penicillin resistance mechanism of clinical Streptococcus pneumoniae isolates at the strain level. To explore the possibilities of studying the mechanism based on the sequence types (ST) of this bacteria, 488 isolates collected in Beijing from 1997-2014 and 88 isolates collected in Youyang County, Chongqing and Zhongjiang County, Sichuan in 2015 were analyzed by penicillin minimum inhibitory concentration (MIC) distribution and annual distribution. The results showed that the penicillin MICs of the all isolates covering by the given ST in Beijing have a defined range, either penicillin MIC penicillin MICs in the first few years after it was identified. The penicillin MIC of isolates identified as common STs and collected in Youyang County, Chongqing and Sichuan Zhongjiang County, including the ST271, ST320 and ST81, was around 0.25~2 mg/L (≥0.25 mg/L). Our study revealed the epidemiological distribution of penicillin MICs of the given STs determined in clinical S. pneumoniae isolates, suggesting that it is reasonable to research the penicillin resistance mechanism based on the STs of this bacteria.

Active mechanics in living oocytes reveal molecular-scale force kinetics

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Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.

Imaging the Antikythera Mechanism

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Malzbender, Thomas

2012-02-10

In 1900, a party of sponge divers chanced on the wreck of a Roman merchant vessel between Crete and mainland Greece. It was found to contain numerous ancient Greek treasures, among them a mysterious lump of clay that split open to reveal ‘mathematical gears’ as it dried out. This object is now known as the Antikythera Mechanism, one of the most enlightening artifacts in terms of revealing the advanced nature of ancient Greek science and technology. In 2005 we travelled to the National Archeological Museum in Athens to apply our Reflectance Imaging methods to the mechanism in the hopes of revealing ancient writing on the device. We were successful, and along with the results of Microfocus CT imaging, epigraphers were able to decipher 3000 characters.

Evidence for participation of GCS1 in fertilization of the starlet sea anemone Nematostella vectensis: Implication of a common mechanism of sperm–egg fusion in plants and animals

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Ebchuqin, Eerdundagula; Yokota, Naoto; Yamada, Lixy [Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, Sugashima, Toba 517-0004 (Japan); Yasuoka, Yuuri [Marine Genomics Unit, Okinawa Institute of Science and Technology, Onna, Okinawa 904-0495 (Japan); Akasaka, Mari [Laboratory of Molecular Genetics, Graduate School of Science, Nagoya University, Chikusa-ku, Furo-cho, Nagoya 464-8602 (Japan); Arakawa, Mio; Deguchi, Ryusaku [Department of Biology, Miyagi University of Education, Sendai, Miyagi 980-0845 (Japan); Mori, Toshiyuki [Waseda Institute for Advanced Study, Waseda University, Shinjuku, Tokyo 169-8050 (Japan); Sawada, Hitoshi, E-mail: hsawada@bio.nagoya-u.ac.jp [Sugashima Marine Biological Laboratory, Graduate School of Science, Nagoya University, Sugashima, Toba 517-0004 (Japan)

2014-09-05

Highlights: • GCS1 is a sperm transmembrane protein that is essential for gamete fusion in flowering plants. • The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals. • NvGCS1 gene is expressed in the testis and GCS1 protein exists in sperm of a sea anemone. • Anti-GCS1 antibodies inhibited the fertilization, showing the participation in fertilization. - Abstract: It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane protein that is exclusively expressed in sperm cells and is essential for gamete fusion in flowering plants. The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals, implying the occurrence of a common or ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the common mechanism, we investigated the role of GCS1 in animal fertilization using a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and the role of GCS1 in fertilization are not known. In this study, we showed that the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by in situ hybridization and proteomic analysis, respectively. Then we made four peptide antibodies against the N-terminal extracellular region of NvGCS1. These antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of Western analysis and potently inhibited fertilization in a concentration-dependent manner. These results indicate that sperm GCS1 plays a pivotal role in fertilization, most probably in sperm–egg fusion, in a starlet sea anemone, suggesting a common gamete-fusion mechanism shared by eukaryotic organisms.

Joint Estimation of Multiple Precision Matrices with Common Structures.

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Lee, Wonyul; Liu, Yufeng

Estimation of inverse covariance matrices, known as precision matrices, is important in various areas of statistical analysis. In this article, we consider estimation of multiple precision matrices sharing some common structures. In this setting, estimating each precision matrix separately can be suboptimal as it ignores potential common structures. This article proposes a new approach to parameterize each precision matrix as a sum of common and unique components and estimate multiple precision matrices in a constrained l 1 minimization framework. We establish both estimation and selection consistency of the proposed estimator in the high dimensional setting. The proposed estimator achieves a faster convergence rate for the common structure in certain cases. Our numerical examples demonstrate that our new estimator can perform better than several existing methods in terms of the entropy loss and Frobenius loss. An application to a glioblastoma cancer data set reveals some interesting gene networks across multiple cancer subtypes.

Real-time single-molecule tethered particle motion experiments reveal the kinetics and mechanisms of Cre-mediated site-specific recombination

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Fan, Hsiu-Fang

2012-01-01

Tyrosine family recombinases (YRs) are widely utilized in genome engineering systems because they can easily direct DNA rearrangement. Cre recombinases, one of the most commonly used types of YRs, catalyze site-specific recombination between two loxP sites without the need for high-energy cofactors, other accessory proteins or a specific DNA target sequence between the loxP sites. Previous structural, analytical ultracentrifuge and electrophoretic analyses have provided details of the reaction kinetics and mechanisms of Cre recombinase activity; whether there are reaction intermediates or side pathways involved has been left unaddressed. Using tethered particle motion (TPM), the Cre-mediated site-specific recombination process has been delineated, from beginning to end, at the single-molecule level, including the formation of abortive complexes and wayward complexes blocking inactive nucleoprotein complexes from entering the recombination process. Reversibility in the strand-cleavage/-ligation process and the formation of a thermally stable Holliday junction intermediate were observed within the Cre-mediated site-specific recombination process. Rate constants for each elementary step, which explain the overall reaction outcomes under various conditions, were determined. Taking the findings of this study together, they demonstrate the potential of single-molecule methodology as an alternative approach for exploring reaction mechanisms in detail. PMID:22467208

Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms.

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Elizabeth D Hutchins

Full Text Available Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.

Crowdsourcing cyber security: a property rights view of exclusion and theft on the information commons

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Gary Shiffman

2013-02-01

Full Text Available Individuals increasingly rely upon the internet for basic economic interaction. Current cyber security mechanisms are unable to stop adversaries and hackers from gaining access to sensitive information stored on government, business, and public computers. Experts propose implementing attribution and audit frameworks in cyberspace to deter, prevent, and prosecute cyber criminals and attackers. However, this method faces significant policy and resource constraints. Social science research, specifically in law and economics, concerning common-pool resources suggests an organic approach to cyber security may yield an appropriate solution. This cyber commons method involves treating the internet as a commons and encouraging individuals and institutions to voluntarily implement innovative and adaptive monitoring mechanisms. Such mechanisms are already in use and in many cases have proven more effective than attribution mechanisms in resisting and tracing the source of cyber attacks.

The structural pathway of interleukin 1 (IL-1 initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer.

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Saliha Ece Acuner Ozbabacan

2014-02-01

Full Text Available Interleukin-1 (IL-1 is a large cytokine family closely related to innate immunity and inflammation. IL-1 proteins are key players in signaling pathways such as apoptosis, TLR, MAPK, NLR and NF-κB. The IL-1 pathway is also associated with cancer, and chronic inflammation increases the risk of tumor development via oncogenic mutations. Here we illustrate that the structures of interfaces between proteins in this pathway bearing the mutations may reveal how. Proteins are frequently regulated via their interactions, which can turn them ON or OFF. We show that oncogenic mutations are significantly at or adjoining interface regions, and can abolish (or enhance the protein-protein interaction, making the protein constitutively active (or inactive, if it is a repressor. We combine known structures of protein-protein complexes and those that we have predicted for the IL-1 pathway, and integrate them with literature information. In the reconstructed pathway there are 104 interactions between proteins whose three dimensional structures are experimentally identified; only 15 have experimentally-determined structures of the interacting complexes. By predicting the protein-protein complexes throughout the pathway via the PRISM algorithm, the structural coverage increases from 15% to 71%. In silico mutagenesis and comparison of the predicted binding energies reveal the mechanisms of how oncogenic and single nucleotide polymorphism (SNP mutations can abrogate the interactions or increase the binding affinity of the mutant to the native partner. Computational mapping of mutations on the interface of the predicted complexes may constitute a powerful strategy to explain the mechanisms of activation/inhibition. It can also help explain how an oncogenic mutation or SNP works.

An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance.

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Xu, Yongchang; Wei, Wenhui; Lei, Sheng; Lin, Jingxia; Srinivas, Swaminath; Feng, Youjun

2018-04-10

Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA , the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli , Salmonella enterica , Klebsiella pneumoniae , etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and p hospho e thanol a mine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens. IMPORTANCE EptA and MCR-1 and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a final resort against carbapenem-resistant pathogens. Structural and functional analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing cavities, which explains intrinsic and

Kinetic mechanism of human DNA ligase I reveals magnesium-dependent changes in the rate-limiting step that compromise ligation efficiency.

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Taylor, Mark R; Conrad, John A; Wahl, Daniel; O'Brien, Patrick J

2011-07-01

DNA ligase I (LIG1) catalyzes the ligation of single-strand breaks to complete DNA replication and repair. The energy of ATP is used to form a new phosphodiester bond in DNA via a reaction mechanism that involves three distinct chemical steps: enzyme adenylylation, adenylyl transfer to DNA, and nick sealing. We used steady state and pre-steady state kinetics to characterize the minimal mechanism for DNA ligation catalyzed by human LIG1. The ATP dependence of the reaction indicates that LIG1 requires multiple Mg(2+) ions for catalysis and that an essential Mg(2+) ion binds more tightly to ATP than to the enzyme. Further dissection of the magnesium ion dependence of individual reaction steps revealed that the affinity for Mg(2+) changes along the reaction coordinate. At saturating concentrations of ATP and Mg(2+) ions, the three chemical steps occur at similar rates, and the efficiency of ligation is high. However, under conditions of limiting Mg(2+), the nick-sealing step becomes rate-limiting, and the adenylylated DNA intermediate is prematurely released into solution. Subsequent adenylylation of enzyme prevents rebinding to the adenylylated DNA intermediate comprising an Achilles' heel of LIG1. These ligase-generated 5'-adenylylated nicks constitute persistent breaks that are a threat to genomic stability if they are not repaired. The kinetic and thermodynamic framework that we have determined for LIG1 provides a starting point for understanding the mechanism and specificity of mammalian DNA ligases.

A comparison of two common sample preparation techniques for lipid and fatty acid analysis in three different coral morphotypes reveals quantitative and qualitative differences.

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Conlan, Jessica A; Rocker, Melissa M; Francis, David S

2017-01-01

Lipids are involved in a host of biochemical and physiological processes in corals. Therefore, changes in lipid composition reflect changes in the ecology, nutrition, and health of corals. As such, accurate lipid extraction, quantification, and identification is critical to obtain comprehensive insight into a coral's condition. However, discrepancies exist in sample preparation methodology globally, and it is currently unknown whether these techniques generate analogous results. This study compared the two most common sample preparation techniques for lipid analysis in corals: (1) tissue isolation by air-spraying and (2) crushing the coral in toto . Samples derived from each preparation technique were subsequently analysed to quantify lipids and their constituent classes and fatty acids in four common, scleractinian coral species representing three distinct morphotypes ( Acropora millepora , Montipora crassotuberculata , Porites cylindrica , and Pocillopora damicornis ). Results revealed substantial amounts of organic material, including lipids, retained in the skeletons of all species following air-spraying, causing a marked underestimation of total lipid concentration using this method. Moreover, lipid class and fatty acid compositions between the denuded skeleton and sprayed tissue were substantially different. In particular, the majority of the total triacylglycerol and total fatty acid concentrations were retained in the skeleton (55-69% and 56-64%, respectively). As such, the isolated, sprayed tissue cannot serve as a reliable proxy for lipid quantification or identification in the coral holobiont. The in toto crushing method is therefore recommended for coral sample preparation prior to lipid analysis to capture the lipid profile of the entire holobiont, permitting accurate diagnoses of coral condition.

A comparison of two common sample preparation techniques for lipid and fatty acid analysis in three different coral morphotypes reveals quantitative and qualitative differences

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Jessica A. Conlan

2017-08-01

Full Text Available Lipids are involved in a host of biochemical and physiological processes in corals. Therefore, changes in lipid composition reflect changes in the ecology, nutrition, and health of corals. As such, accurate lipid extraction, quantification, and identification is critical to obtain comprehensive insight into a coral’s condition. However, discrepancies exist in sample preparation methodology globally, and it is currently unknown whether these techniques generate analogous results. This study compared the two most common sample preparation techniques for lipid analysis in corals: (1 tissue isolation by air-spraying and (2 crushing the coral in toto. Samples derived from each preparation technique were subsequently analysed to quantify lipids and their constituent classes and fatty acids in four common, scleractinian coral species representing three distinct morphotypes (Acropora millepora, Montipora crassotuberculata, Porites cylindrica, and Pocillopora damicornis. Results revealed substantial amounts of organic material, including lipids, retained in the skeletons of all species following air-spraying, causing a marked underestimation of total lipid concentration using this method. Moreover, lipid class and fatty acid compositions between the denuded skeleton and sprayed tissue were substantially different. In particular, the majority of the total triacylglycerol and total fatty acid concentrations were retained in the skeleton (55–69% and 56–64%, respectively. As such, the isolated, sprayed tissue cannot serve as a reliable proxy for lipid quantification or identification in the coral holobiont. The in toto crushing method is therefore recommended for coral sample preparation prior to lipid analysis to capture the lipid profile of the entire holobiont, permitting accurate diagnoses of coral condition.

Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

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Peter Rellos

2010-07-01

Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

Towards a taxonomy of common factors in psychotherapy-results of an expert survey.

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Tschacher, Wolfgang; Junghan, Ulrich Martin; Pfammatter, Mario

2014-01-01

How change comes about is hotly debated in psychotherapy research. One camp considers 'non-specific' or 'common factors', shared by different therapy approaches, as essential, whereas researchers of the other camp consider specific techniques as the essential ingredients of change. This controversy, however, suffers from unclear terminology and logical inconsistencies. The Taxonomy Project therefore aims at contributing to the definition and conceptualization of common factors of psychotherapy by analyzing their differential associations to standard techniques. A review identified 22 common factors discussed in psychotherapy research literature. We conducted a survey, in which 68 psychotherapy experts assessed how common factors are implemented by specific techniques. Using hierarchical linear models, we predicted each common factor by techniques and by experts' age, gender and allegiance to a therapy orientation. Common factors differed largely in their relevance for technique implementation. Patient engagement, Affective experiencing and Therapeutic alliance were judged most relevant. Common factors also differed with respect to how well they could be explained by the set of techniques. We present detailed profiles of all common factors by the (positively or negatively) associated techniques. There were indications of a biased taxonomy not covering the embodiment of psychotherapy (expressed by body-centred techniques such as progressive muscle relaxation, biofeedback training and hypnosis). Likewise, common factors did not adequately represent effective psychodynamic and systemic techniques. This taxonomic endeavour is a step towards a clarification of important core constructs of psychotherapy. This article relates standard techniques of psychotherapy (well known to practising therapists) to the change factors/change mechanisms discussed in psychotherapy theory. It gives a short review of the current debate on the mechanisms by which psychotherapy works. We

Obesity and psychotic disorders: uncovering common mechanisms through metabolomics

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Matej Orešič

2012-09-01

Full Text Available Primary obesity and psychotic disorders are similar with respect to the associated changes in energy balance and co-morbidities, including metabolic syndrome. Such similarities do not necessarily demonstrate causal links, but instead suggest that specific causes of and metabolic disturbances associated with obesity play a pathogenic role in the development of co-morbid disorders, potentially even before obesity develops. Metabolomics – the systematic study of metabolites, which are small molecules generated by the process of metabolism – has been important in elucidating the pathways underlying obesity-associated co-morbidities. This review covers how recent metabolomic studies have advanced biomarker discovery and the elucidation of mechanisms underlying obesity and its co-morbidities, with a specific focus on metabolic syndrome and psychotic disorders. The importance of identifying metabolic markers of disease-associated intermediate phenotypes – traits modulated but not encoded by the DNA sequence – is emphasized. Such markers would be applicable as diagnostic tools in a personalized healthcare setting and might also open up novel therapeutic avenues.

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes.

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Thybert, David; Roller, Maša; Navarro, Fábio C P; Fiddes, Ian; Streeter, Ian; Feig, Christine; Martin-Galvez, David; Kolmogorov, Mikhail; Janoušek, Václav; Akanni, Wasiu; Aken, Bronwen; Aldridge, Sarah; Chakrapani, Varshith; Chow, William; Clarke, Laura; Cummins, Carla; Doran, Anthony; Dunn, Matthew; Goodstadt, Leo; Howe, Kerstin; Howell, Matthew; Josselin, Ambre-Aurore; Karn, Robert C; Laukaitis, Christina M; Jingtao, Lilue; Martin, Fergal; Muffato, Matthieu; Nachtweide, Stefanie; Quail, Michael A; Sisu, Cristina; Stanke, Mario; Stefflova, Klara; Van Oosterhout, Cock; Veyrunes, Frederic; Ward, Ben; Yang, Fengtang; Yazdanifar, Golbahar; Zadissa, Amonida; Adams, David J; Brazma, Alvis; Gerstein, Mark; Paten, Benedict; Pham, Son; Keane, Thomas M; Odom, Duncan T; Flicek, Paul

2018-04-01

Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli , which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology. © 2018 Thybert et al.; Published by Cold Spring Harbor Laboratory Press.

Common approach to common interests

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-06-01

In referring to issues confronting the energy field in this region and options to be exercised in the future, I would like to mention the fundamental condition of the utmost importance. That can be summed up as follows: any subject in energy area can never be solved by one country alone, given the geographical and geopolitical characteristics intrinsically possessed by energy. So, a regional approach is needed and it is especially necessary for the main players in the region to jointly address problems common to them. Though it may be a matter to be pursued in the distant future, I am personally dreaming a 'Common Energy Market for Northeast Asia,' in which member countries' interests are adjusted so that the market can be integrated and the region can become a most economically efficient market, thus formulating an effective power to encounter the outside. It should be noted that Europe needed forty years to integrate its market as the unified common market. It is necessary for us to follow a number of steps over the period to eventually materialize our common market concept, too. Now is the time for us to take a first step to lay the foundation for our descendants to enjoy prosperity from such a common market.

Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction

Science.gov (United States)

Tulpule, Asmin; Kelley, James M.; Lensch, M. William; McPherson, Jade; Park, In Hyun; Hartung, Odelya; Nakamura, Tomoka; Schlaeger, Thorsten M.; Shimamura, Akiko; Daley, George Q.

2013-01-01

Summary Shwachman-Diamond syndrome (SDS), a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction, is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. We created human pluripotent stem cell models of SDS by knock-down of SBDS in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two SDS patients. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. Protease-mediated auto-digestion provides a mechanistic link between the pancreatic and hematopoietic phenotypes in SDS, highlighting the utility of hESCs and iPSCs in obtaining novel insights into human disease. PMID:23602541

Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?

Science.gov (United States)

Morgan, William F.

2003-01-01

A number of nontargeted and delayed effects associated with radiation exposure have now been described. These include radiation-induced genomic instability, death-inducing and bystander effects, clastogenic factors and transgenerational effects. It is unlikely that these nontargeted effects are directly induced by cellular irradiation. Instead, it is proposed that some as yet to be identified secreted factor can be produced by irradiated cells that can stimulate effects in nonirradiated cells (death-inducing and bystander effects, clastogenic factors) and perpetuate genomic instability in the clonally expanded progeny of an irradiated cell. The proposed factor must be soluble and capable of being transported between cells by cell-to-cell gap junction communication channels. Furthermore, it must have the potential to stimulate cellular cytokines and/or reactive oxygen species. While it is difficult to imagine a role for such a secreted factor in contributing to transgenerational effects, the other nontargeted effects of radiation may all share a common mechanism.

Transcriptional analysis and molecular dynamics simulations reveal the mechanism of toxic metals removal and efflux pumps in Lysinibacillus sphaericus OT4b.31

KAUST Repository

Shaw, Dario Rangel

2017-11-23

Lysinibacillus sphaericus strain OT4b.31 is a bacterium widely applied in bioremediation processes of hydrocarbon and metal polluted environments. In this study, we identified the molecular mechanism underlying the Pb2+ and Cr6+ resistance. Metal uptake and temporal transcription patterns of metal resistance operons were evaluated using reverse-transcribed quantitative PCR amplification. The function of the resistance determinants was studied applying docking and in silico mutagenesis methods. The results revealed that the adaptation of Lysinibacillus sphaericus OT4b.31 to elevated levels of lead and chromium involves the pbr and chr operons which comprise a transcriptional regulatory component (pbrR and chrB) and efflux ATPases (pbrA and chrA) to expel ions from the cytoplasm. Expression of metal resistance genes was constitutive and specifically inducible to the exposure of Pb2+ and Cr6+. The simultaneous presence of cations didn\\'t affect the bioaccumulation of metals, evidencing the multimetal resistance of L. sphaericus. Docking analysis revealed the key metal-protein interactions and the conformational changes after metal or ATP binding. Results showed that residues with aromatic rings or imidazole in the catalytic domain are crucial for metal binding and achievement of the function. To our knowledge, this is the first report of a specific mechanism for lead and chromium resistance in Lysinibacillus genus. From the findings of this study, it is possible to suggest the bacterium as a suitable candidate for rapid toxic metals bioremediation processes.

Common Courses for Common Purposes:

DEFF Research Database (Denmark)

Schaub Jr, Gary John

2014-01-01

(PME)? I suggest three alternative paths that increased cooperation in PME at the level of the command and staff course could take: a Nordic Defence College, standardized national command and staff courses, and a core curriculum of common courses for common purposes. I conclude with a discussion of how...

From Blame to Punishment: Disrupting Prefrontal Cortex Activity Reveals Norm Enforcement Mechanisms.

Science.gov (United States)

Buckholtz, Joshua W; Martin, Justin W; Treadway, Michael T; Jan, Katherine; Zald, David H; Jones, Owen; Marois, René

2015-09-23

The social welfare provided by cooperation depends on the enforcement of social norms. Determining blameworthiness and assigning a deserved punishment are two cognitive cornerstones of norm enforcement. Although prior work has implicated the dorsolateral prefrontal cortex (DLPFC) in norm-based judgments, the relative contribution of this region to blameworthiness and punishment decisions remains poorly understood. Here, we used repetitive transcranial magnetic stimulation (rTMS) and fMRI to determine the specific role of DLPFC function in norm-enforcement behavior. DLPFC rTMS reduced punishment for wrongful acts without affecting blameworthiness ratings, and fMRI revealed punishment-selective DLPFC recruitment, suggesting that these two facets of norm-based decision making are neurobiologically dissociable. Finally, we show that DLPFC rTMS affects punishment decision making by altering the integration of information about culpability and harm. Together, these findings reveal a selective, causal role for DLPFC in norm enforcement: representational integration of the distinct information streams used to make punishment decisions. Copyright © 2015 Elsevier Inc. All rights reserved.

High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia

OpenAIRE

Drewes, Julia L.; White, James R.; Dejea, Christine M.; Fathi, Payam; Iyadorai, Thevambiga; Vadivelu, Jamuna; Roslani, April C.; Wick, Elizabeth C.; Mongodin, Emmanuel F.; Loke, Mun Fai; Thulasi, Kumar; Gan, Han Ming; Goh, Khean Lee; Chong, Hoong Yin; Kumar, Sandip

2017-01-01

Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences i...

Discriminative topological features reveal biological network mechanisms

Directory of Open Access Journals (Sweden)

Levovitz Chaya

2004-11-01

Full Text Available Abstract Background Recent genomic and bioinformatic advances have motivated the development of numerous network models intending to describe graphs of biological, technological, and sociological origin. In most cases the success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree distributions, mean geodesic lengths, and clustering coefficients. Often pairs of models can reproduce these features with indistinguishable fidelity despite being generated by vastly different mechanisms. In such cases, these few target features are insufficient to distinguish which of the different models best describes real world networks of interest; moreover, it is not clear a priori that any of the presently-existing algorithms for network generation offers a predictive description of the networks inspiring them. Results We present a method to assess systematically which of a set of proposed network generation algorithms gives the most accurate description of a given biological network. To derive discriminative classifiers, we construct a mapping from the set of all graphs to a high-dimensional (in principle infinite-dimensional "word space". This map defines an input space for classification schemes which allow us to state unambiguously which models are most descriptive of a given network of interest. Our training sets include networks generated from 17 models either drawn from the literature or introduced in this work. We show that different duplication-mutation schemes best describe the E. coli genetic network, the S. cerevisiae protein interaction network, and the C. elegans neuronal network, out of a set of network models including a linear preferential attachment model and a small-world model. Conclusions Our method is a first step towards systematizing network models and assessing their predictability, and we anticipate its usefulness for a number of communities.

Whole transcriptome analysis reveals potential novel mechanisms of low-level linezolid resistance in Enterococcus faecalis.

Science.gov (United States)

Hua, Ruoyi; Xia, Yun; Wu, Wenyao; Yan, Jia; Yang, Mi

2018-03-20

Linezolid is an oxazolidinone antibiotic commonly used to treat serious infections caused by vancomycin-resistant enterococcus. Recently, low-level linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the resistant mechanisms remain undefined. Whole-transcriptome profiling was performed on an E. faecalis strain P10748 with low-level linezolid resistance in comparison with a linezolid-susceptible strain 3138 and the standard control strain ATCC29212. The functions of differentially expressed genes (DEGs) were predicted, with some DEGs potentially involved in drug resistance were validated by PCR and quantitative PCR (qPCR). RNA-Seq on three E. faecalis strains generated 1920 unigenes, with 98% of them assigned to various function groups. A total of 150 DEGs were identified in the linezolid resistant strain P10748 compared to the linezolid susceptible strains 3138 and ATCC29212. Functional analysis indicated a significant transcriptomic shift to membrane transportation and biofilm formation in strain P10748, with three significantly up-regulated DEGs predicted to be associated with drug resistance through active efflux pumps and biofilm formation. The existence of these three DEGs was further confirmed by PCR and qPCR. The significant upregulation of genes associated with efflux pumps and biofilm formation in the linezolid resistant strain suggests their roles in low-level resistance to linezolid in E. faecalis. Copyright © 2018. Published by Elsevier B.V.

Co-culture microorganisms with different initial proportions reveal the mechanism of chalcopyrite bioleaching coupling with microbial community succession.

Science.gov (United States)

Ma, Liyuan; Wang, Xingjie; Feng, Xue; Liang, Yili; Xiao, Yunhua; Hao, Xiaodong; Yin, Huaqun; Liu, Hongwei; Liu, Xueduan

2017-01-01

The effect of co-culture microorganisms with different initial proportions on chalcopyrite bioleaching was investigated. Communities were rebuilt by six typical strains isolated from the same habitat. The results indicated, by community with more sulfur oxidizers at both 30 and 40°C, the final copper extraction rate was 19.8% and 6.5% higher, respectively, than that with more ferrous oxidizers. The variations of pH, redox potential, ferrous and copper ions in leachate also provided evidences that community with more sulfur oxidizers was more efficient. Community succession of free and attached cells revealed that initial proportions played decisive roles on community dynamics at 30°C, while communities shared similar structures, not relevant to initial proportions at 40°C. X-ray diffraction analysis confirmed different microbial functions on mineral surface. A mechanism model for chalcopyrite bioleaching was established coupling with community succession. This will provide theoretical basis for reconstructing an efficient community in industrial application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Camelid genomes reveal evolution and adaptation to desert environments.

Science.gov (United States)

Wu, Huiguang; Guang, Xuanmin; Al-Fageeh, Mohamed B; Cao, Junwei; Pan, Shengkai; Zhou, Huanmin; Zhang, Li; Abutarboush, Mohammed H; Xing, Yanping; Xie, Zhiyuan; Alshanqeeti, Ali S; Zhang, Yanru; Yao, Qiulin; Al-Shomrani, Badr M; Zhang, Dong; Li, Jiang; Manee, Manee M; Yang, Zili; Yang, Linfeng; Liu, Yiyi; Zhang, Jilin; Altammami, Musaad A; Wang, Shenyuan; Yu, Lili; Zhang, Wenbin; Liu, Sanyang; Ba, La; Liu, Chunxia; Yang, Xukui; Meng, Fanhua; Wang, Shaowei; Li, Lu; Li, Erli; Li, Xueqiong; Wu, Kaifeng; Zhang, Shu; Wang, Junyi; Yin, Ye; Yang, Huanming; Al-Swailem, Abdulaziz M; Wang, Jun

2014-10-21

Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

Study of ethanol-induced Golgi disorganization reveals the potential mechanism of alcohol-impaired N-glycosylation

Science.gov (United States)

Casey, Carol A.; Bhat, Ganapati; Holzapfel, Melissa S.; Petrosyan, Armen

2016-01-01

Background It is known that ethanol (EtOH) and its metabolites have a negative effect on protein glycosylation. The fragmentation of the Golgi apparatus induced by alteration of the structure of largest Golgi matrix protein, giantin, is the major consequence of damaging effects of EtOH-metabolism on the Golgi, however, the link between this and abnormal glycosylation remains unknown. Because previously we have shown that Golgi morphology dictates glycosylation, we examined the effect EtOH administration has on function of Golgi residential enzymes involved in N-glycosylation. Methods HepG2 cells transfected with mouse ADH1 (VA-13 cells) were treated with 35 mM ethanol for 72 h. Male Wistar rats were pair-fed Lieber-DeCarli diets for 5 to 8 weeks. Characterization of Golgi-associated mannosyl (α-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (MGAT1), α-1,2-mannosidase (Man-I) and α-mannosidase II (Man-II) were performed in VA-13 cells and rat hepatocytes followed by 3D Structured Illumination Microscopy (SIM). Results First, we detected that EtOH administration results in the loss of sialylated N-glycans on asialoglycoprotein receptor, however the high mannose-type N-glycans are increased. Further analysis by 3D SIM microscopy revealed that EtOH treatment despite Golgi disorganization does not change cis-Golgi localization for Man-I, but does induce medial-to-cis relocation of MGAT1 and Man-II. Using different approaches, including electron microscopy, we revealed that EtOH treatment results in dysfunction of Arf1 GTPase followed by a deficiency in COPI vesicles at the Golgi. Silencing beta-COP or expression of GDP-bound mutant Arf1(T31N) mimics the EtOH effect on retaining MGAT1 and Man-II at the cis-Golgi, suggesting that (a) EtOH specifically blocks activation of Arf1, and (b) EtOH alters the proper localization of Golgi enzymes through impairment of COPI. Importantly, the level of MGAT1 was reduced, because likely MGAT1, contrary to Man-I and Man

Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms

Science.gov (United States)

Widdows, Kate L.; Panitchob, Nuttanont; Crocker, Ian P.; Please, Colin P.; Hanson, Mark A.; Sibley, Colin P.; Johnstone, Edward D.; Sengers, Bram G.; Lewis, Rohan M.; Glazier, Jocelyn D.

2015-01-01

Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [14C]l-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]l-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with l-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms. PMID:25761365

Development of a single-layer Nb3Sn common coil dipole model

Energy Technology Data Exchange (ETDEWEB)

Igor Novitski et al.

2002-12-13

A high-field dipole magnet based on the common coil design was developed at Fermilab for a future Very Large Hadron Collider. A short model of this magnet with a design field of 11 T in two 40-mm apertures is being fabricated using the react-and-wind technique. In order to study and optimize the magnet design two 165-mm long mechanical models were assembled and tested. A technological model consisting of magnet straight section and ends was also fabricated in order to check the tooling and the winding and assembly procedures. This paper describes the design and technology of the common coil dipole magnet and summarizes the status of short model fabrication.The results of the mechanical model tests and comparison with FE mechanical analysis are also presented.

Knowing beans: Human mirror mechanisms revealed through motor adaptation

Directory of Open Access Journals (Sweden)

Arthur M Glenberg

2010-11-01

Full Text Available Human mirror mechanisms (MMs respond during both performed and observed action and appear to underlie action goal recognition. We introduce a behavioral procedure for discovering and clarifying functional MM properties: Blindfolded participants repeatedly move beans either toward or away from themselves to induce motor adaptation. Then, the bias for perceiving direction of ambiguous visual movement in depth is measured. Bias is affected by a number of beans moved, b movement direction, and c similarity of the visual stimulus to the hand used to move beans. This cross-modal adaptation pattern supports both the validity of human MMs and functionality of our testing instrument. We also discuss related work that extends the motor adaptation paradigm to investigate contributions of MMs to speech perception and language comprehension.

Quantitative proteomics revealed partial fungistatic mechanism of ammonia against conidial germination of nematode-trapping fungus Arthrobotrys oligospora ATCC24927.

Science.gov (United States)

Liu, Tong; Tian, Dong-Wei; Zou, Li-Juan; Liu, Fang-Yu; Can, Qi-Yan; Yang, Jin-Kui; Xu, Jian-Ping; Huang, Xiao-Wei; Xi, Jia-Qin; Zhu, Ming-Liang; Mo, Ming-He; Zhang, Ke-Qin

2018-05-01

Ammonia is one of the fungistatic factors in soil that can suppress conidial germination, but the molecular mechanism underlying the suppression is unknown. In this study, the proteomes of fungistatic conidia, fresh conidia and germinated conidia of Arthrobotrys oligospora ATCC24927 were determined and quantified. The protein expression profile of fungistatic conidia was significantly different from those in the other two conditions. 281 proteins were down expressed in fungistatic conidia and characterized by GO annotation. Gene transcription analysis and inhibition of puromycin (a protein translation inhibitor) on conidial germination suggested that down expression of 33 protein translation related proteins might well result in repression of protein synthesis and inhibition of conidial germination. In addition, 16 down-expressed proteins were mapped to the Ras/mitogen-activated protein (Ras/MAP) regulatory networks which regulate conidial DNA synthesis. The conidial DNA synthesis was found to be definitely inhibited under by ammonia, and function studies of two Ras/MAP proteins by using knock-out strains provided partial evidence that Ras/MAP pathway regulate the conidial germination. These results suggested that down-expression of Ras/MAP related proteins might result in inhibition of DNA synthesis and finally result in inhibition conidial germination. This study revealed partial fungistatic mechanism of ammonia against conidial germination. Copyright © 2018 Elsevier Ltd. All rights reserved.

Scintigraphy of cysts of the common bile duct in children

International Nuclear Information System (INIS)

Mironov, S.P.; Akopyan, V.G.; Murieva, Z.D.; Tumanyan, G.T.; Mironova, E.S.

1984-01-01

Cyst of the common bile duct, the most frequent variant of cystic dilatation of the extrahepatic biliary tract, represents a serious diagnostic problem. 13 children with cysts of the common bile duct were studied by the method of dynamic scintigraphy with sup(99m)Tc-HIDA. The scintigraphic picture was characterized by the following signs: sacculated or spheroidal dilatation of the common bile duct, dilatation of the left or both lobular bile ducts, absence of the gall bladder visualization. Change of indicators of the hepatic function and the time of interstinal visualization reflects both the disorder of distal parts permeability and the degree of cyst drainage. An experience of radioisotropic cholegraphy application reveals, that the efficiency of preoperational diagnosis of cysts of the common bile duct increases as a result of the more accurate evaluation of the dynamic of improvement of absorptive-excretory hepatic function after different variants of operations

The house spider genome reveals an ancient whole-genome duplication during arachnid evolution.

Science.gov (United States)

Schwager, Evelyn E; Sharma, Prashant P; Clarke, Thomas; Leite, Daniel J; Wierschin, Torsten; Pechmann, Matthias; Akiyama-Oda, Yasuko; Esposito, Lauren; Bechsgaard, Jesper; Bilde, Trine; Buffry, Alexandra D; Chao, Hsu; Dinh, Huyen; Doddapaneni, HarshaVardhan; Dugan, Shannon; Eibner, Cornelius; Extavour, Cassandra G; Funch, Peter; Garb, Jessica; Gonzalez, Luis B; Gonzalez, Vanessa L; Griffiths-Jones, Sam; Han, Yi; Hayashi, Cheryl; Hilbrant, Maarten; Hughes, Daniel S T; Janssen, Ralf; Lee, Sandra L; Maeso, Ignacio; Murali, Shwetha C; Muzny, Donna M; Nunes da Fonseca, Rodrigo; Paese, Christian L B; Qu, Jiaxin; Ronshaugen, Matthew; Schomburg, Christoph; Schönauer, Anna; Stollewerk, Angelika; Torres-Oliva, Montserrat; Turetzek, Natascha; Vanthournout, Bram; Werren, John H; Wolff, Carsten; Worley, Kim C; Bucher, Gregor; Gibbs, Richard A; Coddington, Jonathan; Oda, Hiroki; Stanke, Mario; Ayoub, Nadia A; Prpic, Nikola-Michael; Flot, Jean-François; Posnien, Nico; Richards, Stephen; McGregor, Alistair P

2017-07-31

The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further, we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum. We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions, and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neo-functionalization and/or sub-functionalization since their duplication. Our results reveal that spiders and scorpions are likely the descendants of a polyploid ancestor that lived more than 450 MYA. Given the extensive morphological diversity and ecological adaptations found among these animals, rivaling those of vertebrates, our study of the ancient WGD event in Arachnopulmonata provides a new comparative platform to explore common and divergent evolutionary outcomes of polyploidization events across eukaryotes.

CERBERUS and NSP1 of Lotus japonicus are common symbiosis genes that modulate arbuscular mycorrhiza development.

Science.gov (United States)

Takeda, Naoya; Tsuzuki, Syusaku; Suzaki, Takuya; Parniske, Martin; Kawaguchi, Masayoshi

2013-10-01

Arbuscular mycorrhizal symbiosis (AMS) and root nodule symbiosis (RNS) are mutualistic plant-microbe interactions that confer nutritional benefits to both partners. Leguminous plants possess a common genetic system for intracellular symbiosis with AM fungi and with rhizobia. Here we show that CERBERUS and NSP1, which respectively encode an E3 ubiquitin ligase and a GRAS transcriptional regulator and which have previously only been implicated in RNS, are involved in AM fungal infection in Lotus japonicus. Hyphal elongation along the longitudinal axis of the root was reduced in the cerberus mutant, giving rise to a lower colonization level. Knockout of NSP1 decreased the frequency of plants colonized by AM fungi or rhizobia. CERBERUS and NSP1 showed different patterns of expression in response to infection with symbiotic microbes. A low constitutive level of CERBERUS expression was observed in the root and an increased level of NSP1 expression was detected in arbuscule-containing cells. Induction of AM marker gene was triggered in both cerberus and nsp1 mutants by infection with symbiotic microbes; however, the mutants showed a weaker induction of marker gene expression than the wild type, mirroring their lower level of colonization. The common symbiosis genes are believed to act in an early signaling pathway for recognition of symbionts and for triggering early symbiotic responses. Our quantitative analysis of symbiotic phenotypes revealed developmental defects of the novel common symbiosis mutants in both symbioses, which demonstrates that common symbiosis mechanisms also contribute to a range of functions at later or different stages of symbiont infection.

An eco-epidemiological study of Morbilli-related paramyxovirus infection in Madagascar bats reveals host-switching as the dominant macro-evolutionary mechanism.

Science.gov (United States)

Mélade, Julien; Wieseke, Nicolas; Ramasindrazana, Beza; Flores, Olivier; Lagadec, Erwan; Gomard, Yann; Goodman, Steven M; Dellagi, Koussay; Pascalis, Hervé

2016-04-12

An eco-epidemiological investigation was carried out on Madagascar bat communities to better understand the evolutionary mechanisms and environmental factors that affect virus transmission among bat species in closely related members of the genus Morbillivirus, currently referred to as Unclassified Morbilli-related paramyxoviruses (UMRVs). A total of 947 bats were investigated originating from 52 capture sites (22 caves, 18 buildings, and 12 outdoor sites) distributed over different bioclimatic zones of the island. Using RT-PCR targeting the L-polymerase gene of the Paramyxoviridae family, we found that 10.5% of sampled bats were infected, representing six out of seven families and 15 out of 31 species analyzed. Univariate analysis indicates that both abiotic and biotic factors may promote viral infection. Using generalized linear modeling of UMRV infection overlaid on biotic and abiotic variables, we demonstrate that sympatric occurrence of bats is a major factor for virus transmission. Phylogenetic analyses revealed that all paramyxoviruses infecting Malagasy bats are UMRVs and showed little host specificity. Analyses using the maximum parsimony reconciliation tool CoRe-PA, indicate that host-switching, rather than co-speciation, is the dominant macro-evolutionary mechanism of UMRVs among Malagasy bats.

Ribbing disease: Uncommon cause of a common symptom

International Nuclear Information System (INIS)

Damle, Nishikant Avinash; Patnecha, Manish; Kumar, Praveen; Gadodia, Ankur; Subbarao, Kiran; Bal, Chandrasekhar

2011-01-01

Ribbing disease is a rare form of sclerosing dysplasia characterized by benign endosteal and periosteal bone growth confined to the diaphyses of the long bones, usually the tibiae and femora. It occurs after puberty and is more commonly seen in women. The most common presenting symptom is pain that is usually self-limited; however, progression is known. The etiology and optimal treatment for the disease are as yet undefined. We present here the case of a 31-year-old woman with clinical, radiological and bone scan manifestations of Ribbing disease corroborated by bone biopsy. Radiographs demonstrated cortical thickening of the diaphyses of both tibiae. 99mTc-methylene diphosphonate bone scan revealed intense irregular uptake in diaphyseal region of both tibiae. Magnetic resonance imaging showed cortical thickening with bone marrow edema in bilateral tibial diaphysis with minimal adjacent soft tissue edema. Bone biopsy revealed predominantly dense lamellar bone with irregular sized and spaced haversian systems. Serum and urine markers of bone metabolism were within normal limits. The patient was treated with analgesics, and had partial relief from pain. Medullary rimming is the next treatment option in case pain progresses. This report emphasizes the role of bone scan in the diagnosis of this rare condition

Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

KAUST Repository

Bagchi, Samik; Lamendella, Regina; Strutt, Steven; Van Loosdrecht, Mark C. M.; Saikaly, Pascal

2016-01-01

to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all

Philosophy vs the common sense

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V. V. Chernyshov

2017-01-01

Full Text Available The paper deals with the antinomy of philosophy and the common sense. Philosophy emerges as a way of specifically human knowledge, which purposes analytics of the reality of subjective experience. The study reveals that in order to alienate philosophy from the common sense it was essential to revise the understanding of wisdom. The new, philosophical interpretation of wisdom – offered by Pythagoras – has laid the foundation of any future philosophy. Thus, philosophy emerges, alienating itself from the common sense, which refers to the common or collective experience. Moreover, the study examines the role of emotions, conformity and conventionality which they play with respect to the common sense. Next the author focuses on the role of philosophical intuition, guided with principles of rationality, nonconformity and scepticism, which the author professes the foundation stones of any sound philosophy. The common sense, described as deeply routed in the world of human emotions, aims at empathy, as the purpose of philosophy is to provide the rational means of knowledge. Therefore, philosophy uses thinking, keeping the permanent efforts to check and recheck data of its own experience. Thus, the first task of philosophical thinking appears to overcome the suggestion of the common sense, which purposes the social empathy, as philosophical intuition aims at independent thinking, the analytics of subjective experience. The study describes the fundamental principles of the common sense, on the one hand, and those of philosophy, on the other. The author arrives to conclusion that the common sense is unable to exceed the limits of sensual experience. Even there, where it apparently rises to a form of any «spiritual unity», even there it cannot avoid referring to the data of commonly shared sensual experience; though, philosophy, meanwhile, goes beyond sensuality, creating a discourse that would be able to alienate from it, and to make its rational

Quantitative Proteomics Analysis Reveals Novel Insights into Mechanisms of Action of Long Noncoding RNA Hox Transcript Antisense Intergenic RNA (HOTAIR) in HeLa Cells*

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Zheng, Peng; Xiong, Qian; Wu, Ying; Chen, Ying; Chen, Zhuo; Fleming, Joy; Gao, Ding; Bi, Lijun; Ge, Feng

2015-01-01

Long noncoding RNAs (lncRNAs), which have emerged in recent years as a new and crucial layer of gene regulators, regulate various biological processes such as carcinogenesis and metastasis. HOTAIR (Hox transcript antisense intergenic RNA), a lncRNA overexpressed in most human cancers, has been shown to be an oncogenic lncRNA. Here, we explored the role of HOTAIR in HeLa cells and searched for proteins regulated by HOTAIR. To understand the mechanism of action of HOTAIR from a systems perspective, we employed a quantitative proteomic strategy to systematically identify potential targets of HOTAIR. The expression of 170 proteins was significantly dys-regulated after inhibition of HOTAIR, implying that they could be potential targets of HOTAIR. Analysis of this data at the systems level revealed major changes in proteins involved in diverse cellular components, including the cytoskeleton and the respiratory chain. Further functional studies on vimentin (VIM), a key protein involved in the cytoskeleton, revealed that HOTAIR exerts its effects on migration and invasion of HeLa cells, at least in part, through the regulation of VIM expression. Inhibition of HOTAIR leads to mitochondrial dysfunction and ultrastructural alterations, suggesting a novel role of HOTAIR in maintaining mitochondrial function in cancer cells. Our results provide novel insights into the mechanisms underlying the function of HOTAIR in cancer cells. We expect that the methods used in this study will become an integral part of functional studies of lncRNAs. PMID:25762744

Common-Sense Realism and the Unimaginable Otherness of Science

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Bradley Monton

2007-12-01

Full Text Available Bas van Fraassen endorses both common-sense realism — the view, roughly, that the ordinary macroscopic objects that we take to exist actually do exist — and constructive empiricism — the view, roughly, that the aim of science is truth about the observable world. But what happens if common-sense realism and science come into conflict? I argue that it is reasonable to think that they could come into conflict, by giving some motivation for a mental monist solution to the measurement problem of quantum mechanics. I then consider whether, in a situation where science favors the mental monist interpretation, van Fraassen would want to give up common-sense realism or would want to give up science.

Cutaneous fibroma in a captive common snapping turtle (Chelydra serpentina).

Science.gov (United States)

Gonzales-Viera, O; Bauer, G; Bauer, A; Aguiar, L S; Brito, L T; Catão-Dias, J L

2012-11-01

An adult female common snapping turtle (Chelydra serpentina) had a mass on the plantar surface of the right forelimb that was removed surgically. Microscopical examination revealed many spindle cells with mild anisocytosis and anisokaryosis and a surrounding collagenous stroma. There were no mitoses. Immunohistochemistry showed that the spindle cells expressed vimentin, but not desmin. A diagnosis of cutaneous fibroma was made. Tumours are reported uncommonly in chelonian species. Cutaneous fibroma has been diagnosed in an alligator snapping turtle (Macrochelys temminckii), but not previously in a common snapping turtle. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Transcriptome Analysis of Sunflower Genotypes with Contrasting Oxidative Stress Tolerance Reveals Individual- and Combined- Biotic and Abiotic Stress Tolerance Mechanisms.

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Vemanna S Ramu

Full Text Available In nature plants are often simultaneously challenged by different biotic and abiotic stresses. Although the mechanisms underlying plant responses against single stress have been studied considerably, plant tolerance mechanisms under combined stress is not understood. Also, the mechanism used to combat independently and sequentially occurring many number of biotic and abiotic stresses has also not systematically studied. From this context, in this study, we attempted to explore the shared response of sunflower plants to many independent stresses by using meta-analysis of publically available transcriptome data and transcript profiling by quantitative PCR. Further, we have also analyzed the possible role of the genes so identified in contributing to combined stress tolerance. Meta-analysis of transcriptomic data from many abiotic and biotic stresses indicated the common representation of oxidative stress responsive genes. Further, menadione-mediated oxidative stress in sunflower seedlings showed similar pattern of changes in the oxidative stress related genes. Based on this a large scale screening of 55 sunflower genotypes was performed under menadione stress and those contrasting in oxidative stress tolerance were identified. Further to confirm the role of genes identified in individual and combined stress tolerance the contrasting genotypes were individually and simultaneously challenged with few abiotic and biotic stresses. The tolerant hybrid showed reduced levels of stress damage both under combined stress and few independent stresses. Transcript profiling of the genes identified from meta-analysis in the tolerant hybrid also indicated that the selected genes were up-regulated under individual and combined stresses. Our results indicate that menadione-based screening can identify genotypes not only tolerant to multiple number of individual biotic and abiotic stresses, but also the combined stresses.

De novo assembly and characterization of the spleen transcriptome of common carp (Cyprinus carpio) using Illumina paired-end sequencing.

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Li, Guoxi; Zhao, Yinli; Liu, Zhonghu; Gao, Chunsheng; Yan, Fengbin; Liu, Bianzhi; Feng, Jianxin

2015-06-01

Common carp (Cyprinus carpio) is one of the most important aquacultured species of the family Cyprinidae, and breeding this species for disease resistance is becoming more and more important. However, at the genome or transcriptome levels, study of the immunogenetics of disease resistance in the common carp is lacking. In this study, 60,316,906 and 75,200,328 paired-end clean reads were obtained from two cDNA libraries of the common carp spleen by Illumina paired-end sequencing technology. Totally, 130,293 unique transcript fragments (unigenes) were assembled, with an average length of 1400.57 bp. Approximately 105,612 (81.06%) unigenes could be annotated according to their homology with matches in the Nr, Nt, Swiss-Prot, COG, GO, or KEGG databases, and they were found to represent 46,747 non-redundant genes. Comparative analysis showed that 59.82% of the unigenes have significant similarity to zebrafish Refseq proteins. Gene expression comparison revealed that 10,432 and 6889 annotated unigenes were, respectively, up- and down-regulated with at least twofold changes between two developmental stages of the common carp spleen. Gene ontology and KEGG analysis were performed to classify all unigenes into functional categories for understanding gene functions and regulation pathways. In addition, 46,847 simple sequence repeats (SSRs) were detected from 35,618 unigenes, and a large number of single nucleotide polymorphism (SNP) and insertion/deletion (INDEL) sites were identified in the spleen transcriptome of common carp. This study has characterized the spleen transcriptome of the common carp for the first time, providing a valuable resource for a better understanding of the common carp immune system and defense mechanisms. This knowledge will also facilitate future functional studies on common carp immunogenetics that may eventually be applied in breeding programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms.

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Jonna Jalanka-Tuovinen

Full Text Available While our knowledge of the intestinal microbiota during disease is accumulating, basic information of the microbiota in healthy subjects is still scarce. The aim of this study was to characterize the intestinal microbiota of healthy adults and specifically address its temporal stability, core microbiota and relation with intestinal symptoms. We carried out a longitudinal study by following a set of 15 healthy Finnish subjects for seven weeks and regularly assessed their intestinal bacteria and archaea with the Human Intestinal Tract (HIT Chip, a phylogenetic microarray, in conjunction with qPCR analyses. The health perception and occurrence of intestinal symptoms was recorded by questionnaire at each sampling point.A high overall temporal stability of the microbiota was observed. Five subjects showed transient microbiota destabilization, which correlated not only with the intake of antibiotics but also with overseas travelling and temporary illness, expanding the hitherto known factors affecting the intestinal microbiota. We identified significant correlations between the microbiota and common intestinal symptoms, including abdominal pain and bloating. The most striking finding was the inverse correlation between Bifidobacteria and abdominal pain: subjects who experienced pain had over five-fold less Bifidobacteria compared to those without pain. Finally, a novel computational approach was used to define the common core microbiota, highlighting the role of the analysis depth in finding the phylogenetic core and estimating its size. The in-depth analysis suggested that we share a substantial number of our intestinal phylotypes but as they represent highly variable proportions of the total community, many of them often remain undetected.A global and high-resolution microbiota analysis was carried out to determine the temporal stability, the associations with intestinal symptoms, and the individual and common core microbiota in healthy adults. The

Cellular Mechanisms of Action of Drug Abuse on Olfactory Neurons

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Thomas Heinbockel

2015-12-01

Full Text Available Cannabinoids (Δ9-tetrahydrocannabinol are the active ingredient of marijuana (cannabis which is the most commonly abused illicit drug in the USA. In addition to being known and used as recreational drugs, cannabinoids are produced endogenously by neurons in the brain (endocannabinoids and serve as important signaling molecules in the nervous system and the rest of the body. Cannabinoids have been implicated in bodily processes both in health and disease. Recent pharmacological and physiological experiments have described novel aspects of classic brain signaling mechanisms or revealed unknown mechanisms of cellular communication involving the endocannabinoid system. While several forms of signaling have been described for endocannabinoids, the most distinguishing feature of endocannabinoids is their ability to act as retrograde messengers in neural circuits. Neurons in the main olfactory bulb express high levels of cannabinoid receptors. Here, we describe the cellular mechanisms and function of this novel brain signaling system in regulating neural activity at synapses in olfactory circuits. Results from basic research have the potential to provide the groundwork for translating the neurobiology of drug abuse to the realm of the pharmacotherapeutic treatment of addiction, specifically marijuana substance use disorder.

Functional Insights Revealed by the Kinetic Mechanism of CRISPR/Cas9.

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Raper, Austin T; Stephenson, Anthony A; Suo, Zucai

2018-02-28

The discovery of prokaryotic adaptive immunity prompted widespread use of the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) endonuclease Cas9 for genetic engineering. However, its kinetic mechanism remains undefined, and details of DNA cleavage are poorly characterized. Here, we establish a kinetic mechanism of Streptococcus pyogenes Cas9 from guide-RNA binding through DNA cleavage and product release. Association of DNA to the binary complex of Cas9 and guide-RNA is rate-limiting during the first catalytic turnover, while DNA cleavage from a pre-formed ternary complex of Cas9, guide-RNA, and DNA is rapid. Moreover, an extremely slow release of DNA products essentially restricts Cas9 to be a single-turnover enzyme. By simultaneously measuring the contributions of the HNH and RuvC nuclease activities of Cas9 to DNA cleavage, we also uncovered the kinetic basis by which HNH conformationally regulates the RuvC cleavage activity. Together, our results provide crucial kinetic and functional details regarding Cas9 which will inform gene-editing experiments, guide future research to understand off-target DNA cleavage by Cas9, and aid in the continued development of Cas9 as a biotechnological tool.

Common Bile Duct Perforation Due to Tuberculosis: A Case Report

OpenAIRE

Razman Jarmin; Shaharin Shaharuddin

2004-01-01

A young man with HIV presented with biliary peritonitis secondary to spontaneous common bile duct perforation. Investigation revealed that the perforation was due to Mycobacterium tuberculosis. Tuberculosis of the bile duct is uncommon and usually presents with obstructive jaundice due to stricture. Bile duct perforation due to tuberculosis is extremely rare. Its management is discussed.

A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa

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Uyeda Taro QP

2005-03-01

Full Text Available Abstract Background Formins are multidomain proteins defined by a conserved FH2 (formin homology 2 domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1 domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes. Results We present a detailed sequence analysis of the 10 formins (ForA to J identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells. Conclusion Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.

A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa.

Science.gov (United States)

Rivero, Francisco; Muramoto, Tetsuya; Meyer, Ann-Kathrin; Urushihara, Hideko; Uyeda, Taro Q P; Kitayama, Chikako

2005-03-01

Formins are multidomain proteins defined by a conserved FH2 (formin homology 2) domain with actin nucleation activity preceded by a proline-rich FH1 (formin homology 1) domain. Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes. We present a detailed sequence analysis of the 10 formins (ForA to J) identified in the genome of the social amoeba Dictyostelium discoideum. With the exception of ForI and ForC all other formins conform to the domain structure GBD/FH3-FH1-FH2-DAD, where DAD is the Diaphanous autoinhibition domain and GBD/FH3 is the Rho GTPase-binding domain/formin homology 3 domain that we propose to represent a single domain. ForC lacks a FH1 domain, ForI lacks recognizable GBD/FH3 and DAD domains and ForA, E and J have additional unique domains. To establish the relationship between formins of Dictyostelium and other organisms we constructed a phylogenetic tree based on the alignment of FH2 domains. Real-time PCR was used to study the expression pattern of formin genes. Expression of forC, D, I and J increased during transition to multi-cellular stages, while the rest of genes displayed less marked developmental variations. During sexual development, expression of forH and forI displayed a significant increase in fusion competent cells. Our analysis allows some preliminary insight into the functionality of Dictyostelium formins: all isoforms might display actin nucleation activity and, with the exception of ForI, might also be susceptible to autoinhibition and to regulation by Rho GTPases. The architecture GBD/FH3-FH1-FH2-DAD appears common to almost all Dictyostelium, fungal and metazoan formins, for which we propose the denomination of conventional formins, and implies a common regulatory mechanism.

Mapping and Genetic Structure Analysis of the Anthracnose Resistance Locus Co-1HY in the Common Bean (Phaseolus vulgaris L..

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Mingli Chen

Full Text Available Anthracnose is a destructive disease of the common bean (Phaseolus vulgaris L.. The Andean cultivar Hongyundou has been demonstrated to possess strong resistance to anthracnose race 81. To study the genetics of this resistance, the Hongyundou cultivar was crossed with a susceptible genotype Jingdou. Segregation of resistance for race 81 was assessed in the F2 population and F2:3 lines under controlled conditions. Results indicate that Hongyundou carries a single dominant gene for anthracnose resistance. An allele test by crossing Hongyundou with another resistant cultivar revealed that the resistance gene is in the Co-1 locus (therefore named Co-1HY. The physical distance between this locus and the two flanking markers was 46 kb, and this region included four candidate genes, namely, Phvul.001G243500, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. These candidate genes encoded serine/threonine-protein kinases. Expression analysis of the four candidate genes in the resistant and susceptible cultivars under control condition and inoculated treatment revealed that all the four candidate genes are expressed at significantly higher levels in the resistant genotype than in susceptible genotype. Phvul.001G243600 and Phvul.001G243700 are expressed nearly 15-fold and 90-fold higher in the resistant genotype than in the susceptible parent before inoculation, respectively. Four candidate genes will provide useful information for further research into the resistance mechanism of anthracnose in common bean. The closely linked flanking markers identified here may be useful for transferring the resistance allele Co-1HY from Hongyundou to elite anthracnose susceptible common bean lines.

Mapping and Genetic Structure Analysis of the Anthracnose Resistance Locus Co-1HY in the Common Bean (Phaseolus vulgaris L.).

Science.gov (United States)

Chen, Mingli; Wu, Jing; Wang, Lanfen; Mantri, Nitin; Zhang, Xiaoyan; Zhu, Zhendong; Wang, Shumin

2017-01-01

Anthracnose is a destructive disease of the common bean (Phaseolus vulgaris L.). The Andean cultivar Hongyundou has been demonstrated to possess strong resistance to anthracnose race 81. To study the genetics of this resistance, the Hongyundou cultivar was crossed with a susceptible genotype Jingdou. Segregation of resistance for race 81 was assessed in the F2 population and F2:3 lines under controlled conditions. Results indicate that Hongyundou carries a single dominant gene for anthracnose resistance. An allele test by crossing Hongyundou with another resistant cultivar revealed that the resistance gene is in the Co-1 locus (therefore named Co-1HY). The physical distance between this locus and the two flanking markers was 46 kb, and this region included four candidate genes, namely, Phvul.001G243500, Phvul.001G243600, Phvul.001G243700 and Phvul.001G243800. These candidate genes encoded serine/threonine-protein kinases. Expression analysis of the four candidate genes in the resistant and susceptible cultivars under control condition and inoculated treatment revealed that all the four candidate genes are expressed at significantly higher levels in the resistant genotype than in susceptible genotype. Phvul.001G243600 and Phvul.001G243700 are expressed nearly 15-fold and 90-fold higher in the resistant genotype than in the susceptible parent before inoculation, respectively. Four candidate genes will provide useful information for further research into the resistance mechanism of anthracnose in common bean. The closely linked flanking markers identified here may be useful for transferring the resistance allele Co-1HY from Hongyundou to elite anthracnose susceptible common bean lines.

Study of male–mediated gene flow across a hybrid zone in the common shrew (Sorex araneus using Y chromosome

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Andrei V. Polyakov

2017-06-01

Full Text Available Despite many studies, the impact of chromosome rearrangements on gene flow between chromosome races of the common shrew (Sorex araneus Linnaeus, 1758 remains unclear. Interracial hybrids form meiotic chromosome complexes that are associated with reduced fertility. Nevertheless comprehensive investigations of autosomal and mitochondrial markers revealed weak or no barrier to gene flow between chromosomally divergent populations. In a narrow zone of contact between the Novosibirsk and Tomsk races hybrids are produced with extraordinarily complex configurations at meiosis I. Microsatellite markers have not revealed any barrier to gene flow, but the phenotypic differentiation between races is greater than may be expected if gene flow was unrestricted. To explore this contradiction we analyzed the distribution of the Y chromosome SNP markers within this hybrid zone. The Y chromosome variants in combination with race specific autosome complements allow backcrosses to be distinguished and their proportion among individuals within the hybrid zone to be evaluated. The balanced ratio of the Y variants observed among the pure race individuals as well as backcrosses reveals no male mediated barrier to gene flow. The impact of reproductive unfitness of backcrosses on gene flow is discussed as a possible mechanism of the preservation of race-specific morphology within the hybrid zone.

Body-induced vortical flows: a common mechanism for self-corrective trimming control in boxfishes.

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Bartol, Ian K; Gharib, Morteza; Webb, Paul W; Weihs, Daniel; Gordon, Malcolm S

2005-01-01

: they produce trimming self-correcting forces, which we measured directly using the force balance. These data together with previous work on smooth trunkfish indicate that body-induced vortical flows are a common mechanism that is probably significant for trim control in all species of tropical boxfishes.

The complete genome sequence of Bacillus velezensis 9912D reveals its biocontrol mechanism as a novel commercial biological fungicide agent.

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Pan, Hua-Qi; Li, Qing-Lian; Hu, Jiang-Chun

2017-04-10

A Bacillus sp. 9912 mutant, 9912D, was approved as a new biological fungicide agent by the Ministry of Agriculture of the People's Republic of China in 2016 owing to its excellent inhibitory effect on various plant pathogens and being environment-friendly. Here, we present the genome of 9912D with a circular chromosome having 4436 coding DNA sequences (CDSs), and a circular plasmid encoding 59 CDSs. This strain was finally designated as Bacillus velezensis based on phylogenomic analyses. Genome analysis revealed a total of 19 candidate gene clusters involved in secondary metabolite biosynthesis, including potential new type II lantibiotics. The absence of fengycin biosynthetic gene cluster is noteworthy. Our data offer insights into the genetic, biological and physiological characteristics of this strain and aid in deeper understanding of its biocontrol mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

Antimicrobial activity and mechanism of the human milk-sourced peptide Casein201

International Nuclear Information System (INIS)

Zhang, Fan; Cui, Xianwei; Fu, Yanrong; Zhang, Jun; Zhou, Yahui; Sun, Yazhou; Wang, Xing; Li, Yun; Liu, Qianqi; Chen, Ting

2017-01-01

Introduction: Casein201 is one of the human milk sourced peptides that differed significantly in preterm and full-term mothers. This study is designed to demonstrate the biological characteristics, antibacterial activity and mechanisms of Casein201 against common pathogens in neonatal infection. Methodology: The analysis of biological characteristics was done by bioinformatics. Disk diffusion method and flow cytometry were used to detect the antimicrobial activity of Casein201. Killing kinetics of Casein201 was measured using microplate reader. The antimicrobial mechanism of Casein201 was studied by electron microscopy and electrophoresis. Results: Bioinformatics analysis indicates that Casein201 derived from β-casein and showed significant sequence overlap. Antibacterial assays showed Casein201 inhibited the growth of S taphylococcus aureus and Y ersinia enterocolitica. Ultrastructural analyses revealed that the antibacterial activity of Casein201 is through cytoplasmic structures disintegration and bacterial cell envelope alterations but not combination with DNA. Conclusion: We conclude the antimicrobial activity and mechanism of Casein201. Our data demonstrate that Casein201 has potential therapeutic value for the prevention and treatment of pathogens in neonatal infection.

Common Bile Duct Perforation Due to Tuberculosis: A Case Report

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Razman Jarmin

2004-10-01

Full Text Available A young man with HIV presented with biliary peritonitis secondary to spontaneous common bile duct perforation. Investigation revealed that the perforation was due to Mycobacterium tuberculosis. Tuberculosis of the bile duct is uncommon and usually presents with obstructive jaundice due to stricture. Bile duct perforation due to tuberculosis is extremely rare. Its management is discussed.

The Role of Chaperone-subunit Usher Domain Interactions in the Mechanism of Bacterial Pilus Biogenesis Revealed by ESI-MS*

Science.gov (United States)

Morrissey, Bethny; Leney, Aneika C.; Toste Rêgo, Ana; Phan, Gilles; Allen, William J.; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E.; Radford, Sheena E.

2012-01-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species. PMID:22371487

The role of chaperone-subunit usher domain interactions in the mechanism of bacterial pilus biogenesis revealed by ESI-MS.

Science.gov (United States)

Morrissey, Bethny; Leney, Aneika C; Toste Rêgo, Ana; Phan, Gilles; Allen, William J; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E; Radford, Sheena E

2012-07-01

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species.

Memory for conversation and the development of common ground.

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McKinley, Geoffrey L; Brown-Schmidt, Sarah; Benjamin, Aaron S

2017-11-01

Efficient conversation is guided by the mutual knowledge, or common ground, that interlocutors form as a conversation progresses. Characterized from the perspective of commonly used measures of memory, efficient conversation should be closely associated with item memory-what was said-and context memory-who said what to whom. However, few studies have explicitly probed memory to evaluate what type of information is maintained following a communicative exchange. The current study examined how item and context memory relate to the development of common ground over the course of a conversation, and how these forms of memory vary as a function of one's role in a conversation as speaker or listener. The process of developing common ground was positively related to both item and context memory. In addition, content that was spoken was remembered better than content that was heard. Our findings illustrate how memory assessments can complement language measures by revealing the impact that basic conversational processes have on memory for what has been discussed. By taking this approach, we show that not only does the process of forming common ground facilitate communication in the present, but it also promotes an enduring record of that event, facilitating conversation into the future.

Drug Induced Steatohepatitis: An Uncommon Culprit of a Common Disease

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Liane Rabinowich

2015-01-01

Full Text Available Nonalcoholic fatty liver disease (NAFLD is a leading cause of liver disease in developed countries. Its frequency is increasing in the general population mostly due to the widespread occurrence of obesity and the metabolic syndrome. Although drugs and dietary supplements are viewed as a major cause of acute liver injury, drug induced steatosis and steatohepatitis are considered a rare form of drug induced liver injury (DILI. The complex mechanism leading to hepatic steatosis caused by commonly used drugs such as amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids, and others is not fully understood. It relates not only to induction of the metabolic syndrome by some drugs but also to their impact on important molecular pathways including increased hepatocytes lipogenesis, decreased secretion of fatty acids, and interruption of mitochondrial β-oxidation as well as altered expression of genes responsible for drug metabolism. Better familiarity with this type of liver injury is important for early recognition of drug hepatotoxicity and crucial for preventing severe forms of liver injury and cirrhosis. Moreover, understanding the mechanisms leading to drug induced hepatic steatosis may provide much needed clues to the mechanism and potential prevention of the more common form of metabolic steatohepatitis.

Dynamics of a Novel Highly Repetitive CACTA Family in Common Bean (Phaseolus vulgaris

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Dongying Gao

2016-07-01

Full Text Available Transposons are ubiquitous genomic components that play pivotal roles in plant gene and genome evolution. We analyzed two genome sequences of common bean (Phaseolus vulgaris and identified a new CACTA transposon family named pvCACTA1. The family is extremely abundant, as more than 12,000 pvCACTA1 elements were found. To our knowledge, this is the most abundant CACTA family reported thus far. The computational and fluorescence in situ hybridization (FISH analyses indicated that the pvCACTA1 elements were concentrated in terminal regions of chromosomes and frequently generated AT-rich 3 bp target site duplications (TSD, WWW, W is A or T. Comparative analysis of the common bean genomes from two domesticated genetic pools revealed that new insertions or excisions of pvCACTA1 elements occurred after the divergence of the two common beans, and some of the polymorphic elements likely resulted in variation in gene sequences. pvCACTA1 elements were detected in related species but not outside the Phaseolus genus. We calculated the molecular evolutionary rate of pvCACTA1 transposons using orthologous elements that indicated that most transposition events likely occurred before the divergence of the two gene pools. These results reveal unique features and evolution of this new transposon family in the common bean genome.

Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors.

Science.gov (United States)

Klaeger, Susan; Gohlke, Bjoern; Perrin, Jessica; Gupta, Vipul; Heinzlmeir, Stephanie; Helm, Dominic; Qiao, Huichao; Bergamini, Giovanna; Handa, Hiroshi; Savitski, Mikhail M; Bantscheff, Marcus; Médard, Guillaume; Preissner, Robert; Kuster, Bernhard

2016-05-20

Many protein kinases are valid drug targets in oncology because they are key components of signal transduction pathways. The number of clinical kinase inhibitors is on the rise, but these molecules often exhibit polypharmacology, potentially eliciting desired and toxic effects. Therefore, a comprehensive assessment of a compound's target space is desirable for a better understanding of its biological effects. The enzyme ferrochelatase (FECH) catalyzes the conversion of protoporphyrin IX into heme and was recently found to be an off-target of the BRAF inhibitor Vemurafenib, likely explaining the phototoxicity associated with this drug in melanoma patients. This raises the question of whether FECH binding is a more general feature of kinase inhibitors. To address this, we applied a chemical proteomics approach using kinobeads to evaluate 226 clinical kinase inhibitors for their ability to bind FECH. Surprisingly, low or submicromolar FECH binding was detected for 29 of all compounds tested and isothermal dose response measurements confirmed target engagement in cells. We also show that Vemurafenib, Linsitinib, Neratinib, and MK-2461 reduce heme levels in K562 cells, verifying that drug binding leads to a loss of FECH activity. Further biochemical and docking experiments identified the protoporphyrin pocket in FECH as one major drug binding site. Since the genetic loss of FECH activity leads to photosensitivity in humans, our data strongly suggest that FECH inhibition by kinase inhibitors is the molecular mechanism triggering photosensitivity in patients. We therefore suggest that a FECH assay should generally be part of the preclinical molecular toxicology package for the development of kinase inhibitors.

Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories.

Science.gov (United States)

Smith, Douglas H; Hicks, Ramona R; Johnson, Victoria E; Bergstrom, Debra A; Cummings, Diana M; Noble, Linda J; Hovda, David; Whalen, Michael; Ahlers, Stephen T; LaPlaca, Michelle; Tortella, Frank C; Duhaime, Ann-Christine; Dixon, C Edward

2015-11-15

Traumatic brain injury (TBI) is a major public health issue exacting a substantial personal and economic burden globally. With the advent of "big data" approaches to understanding complex systems, there is the potential to greatly accelerate knowledge about mechanisms of injury and how to detect and modify them to improve patient outcomes. High quality, well-defined data are critical to the success of bioinformatics platforms, and a data dictionary of "common data elements" (CDEs), as well as "unique data elements" has been created for clinical TBI research. There is no data dictionary, however, for preclinical TBI research despite similar opportunities to accelerate knowledge. To address this gap, a committee of experts was tasked with creating a defined set of data elements to further collaboration across laboratories and enable the merging of data for meta-analysis. The CDEs were subdivided into a Core module for data elements relevant to most, if not all, studies, and Injury-Model-Specific modules for non-generalizable data elements. The purpose of this article is to provide both an overview of TBI models and the CDEs pertinent to these models to facilitate a common language for preclinical TBI research.

Dermatoses among automobile mechanics in Mansoura, Egypt.

Science.gov (United States)

Abou-ElWafa, Hala Samir; Albadry, Ahmed A; El-Gilany, Abdel-Hady; Ismael, Ahmed Fawzi

2018-01-02

This cross-sectional study was carried out in Mansoura, Egypt to assess the prevalence of occupational dermatoses and their possible risk factors on a convenience sample of car mechanics. Sociodemographic and occupational data were collected, and clinical examination was done. Prevalence of skin diseases was 45.4% and that of exclusively occupational skin diseases was 9.2%. Irritant contact dermatitis, eczema, and tar/oil acne were the most common types (4.6%, 3.1%, 3.1%, respectively). The logistic regression analysis revealed that the risk of occupational dermatoses increased significantly with lack of use of personal protective equipment, longer duration of work, and presence of workplace chemicals (adjusted odds ratio [95% CI] were 7.2 [2.7, 19.0], 4.3 [1.7, 10.9], and 3.7 [1.3, 10.5], respectively). Health education and safety measures are essential for prevention and control of hazardous workplace practices and exposure.

Molecular markers reveal spatially segregated cryptic species in a critically endangered fish, the common skate (Dipturus batis).

Science.gov (United States)

Griffiths, Andrew M; Sims, David W; Cotterell, Stephen P; El Nagar, Aliya; Ellis, Jim R; Lynghammar, Arve; McHugh, Matthew; Neat, Francis C; Pade, Nicolas G; Queiroz, Nuno; Serra-Pereira, Bárbara; Rapp, Toby; Wearmouth, Victoria J; Genner, Martin J

2010-05-22

Many sharks and skates are particularly vulnerable to overfishing because of their large size, slow growth, late maturity and low fecundity. In Europe dramatic population declines have taken place in common skate (Dipturus batis L.), one of the largest demersal fish in regional shelf seas, leading to extirpations from substantial parts of its former range. Here we report the discovery of cryptic species in common skate collected from the northeast Atlantic continental shelf. Data from nuclear microsatellite markers indicated two clearly distinct clades and phylogenetic analysis of mitochondrial DNA sequences demonstrated monophyly of each one of them. Capture locations showed evidence of strong spatial segregation, with one taxon occurring mainly in waters off the southern British Isles and around Rockall, while the other was restricted to more northerly shelf waters. These apparently cryptic species showed overlapping substrate and depth preferences, but distributional limits were closely related to temperature gradients, potentially indicating thermal limits to their distributions. This discovery of hidden diversity within a large, critically endangered marine vertebrate demonstrates how marine biodiversity can be underestimated, even in such a relatively well-studied and heavily exploited region.

Molecular markers reveal spatially segregated cryptic species in a critically endangered fish, the common skate (Dipturus batis)

Science.gov (United States)

Griffiths, Andrew M.; Sims, David W.; Cotterell, Stephen P.; El Nagar, Aliya; Ellis, Jim R.; Lynghammar, Arve; McHugh, Matthew; Neat, Francis C.; Pade, Nicolas G.; Queiroz, Nuno; Serra-Pereira, Bárbara; Rapp, Toby; Wearmouth, Victoria J.; Genner, Martin J.

2010-01-01

Many sharks and skates are particularly vulnerable to overfishing because of their large size, slow growth, late maturity and low fecundity. In Europe dramatic population declines have taken place in common skate (Dipturus batis L.), one of the largest demersal fish in regional shelf seas, leading to extirpations from substantial parts of its former range. Here we report the discovery of cryptic species in common skate collected from the northeast Atlantic continental shelf. Data from nuclear microsatellite markers indicated two clearly distinct clades and phylogenetic analysis of mitochondrial DNA sequences demonstrated monophyly of each one of them. Capture locations showed evidence of strong spatial segregation, with one taxon occurring mainly in waters off the southern British Isles and around Rockall, while the other was restricted to more northerly shelf waters. These apparently cryptic species showed overlapping substrate and depth preferences, but distributional limits were closely related to temperature gradients, potentially indicating thermal limits to their distributions. This discovery of hidden diversity within a large, critically endangered marine vertebrate demonstrates how marine biodiversity can be underestimated, even in such a relatively well-studied and heavily exploited region. PMID:20106849

w∞ algebras, conformal mechanics and black holes

Science.gov (United States)

Cacciatori, Sergio; Klemm, Dietmar; Zanon, Daniela

2000-04-01

We discuss BPS solitons in gauged icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 2, D = 4 supergravity. The solitons represent extremal black holes interpolating between different vacua of anti-de Sitter spaces. The isometry superalgebras are determined and the motion of a superparticle in the extremal black hole background is studied and confronted with superconformal mechanics. We show that the Virasoro symmetry of conformal mechanics, which describes the dynamics of the superparticle near the horizon of the extremal black hole under consideration, extends to a symmetry under the wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> algebra of area-preserving diffeomorphisms. We find that a Virasoro subalgebra of wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> can be associated with the Virasoro algebra of the asymptotic symmetries of AdS 2 . In this way spacetime diffeomorphisms of AdS 2 translate into diffeomorphisms in phase space: our system offers an explicit realization of the AdS 2 /CFT 1 correspondence. Using the dimensionally reduced action, the central charge is computed. Finally, we also present generalizations of superconformal mechanics which are invariant under icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 1 and icons/Journals/Common/calN" ALT="calN" ALIGN="TOP"/> = 2 superextensions of wicons/Journals/Common/infty" ALT="infty" ALIGN="MIDDLE"/> .

Comparative Transcriptome Analyses Reveal Potential Mechanisms of Enhanced Drought Tolerance in Transgenic Salvia Miltiorrhiza Plants Expressing AtDREB1A from Arabidopsis.

Science.gov (United States)

Wei, Tao; Deng, Kejun; Wang, Hongbin; Zhang, Lipeng; Wang, Chunguo; Song, Wenqin; Zhang, Yong; Chen, Chengbin

2018-03-12

In our previous study, drought-resistant transgenic plants of Salvia miltiorrhiza were produced via overexpression of the transcription factor AtDREB1A. To unravel the molecular mechanisms underpinning elevated drought tolerance in transgenic plants, in the present study we compared the global transcriptional profiles of wild-type (WT) and AtDREB1A -expressing transgenic plants using RNA-sequencing (RNA-seq). Using cluster analysis, we identified 3904 differentially expressed genes (DEGs). Compared with WT plants, 423 unigenes were up-regulated in pRD29A::AtDREB1A-31 before drought treatment, while 936 were down-regulated and 1580 and 1313 unigenes were up- and down-regulated after six days of drought. COG analysis revealed that the 'signal transduction mechanisms' category was highly enriched among these DEGs both before and after drought stress. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, DEGs associated with "ribosome", "plant hormone signal transduction", photosynthesis", "plant-pathogen interaction", "glycolysis/gluconeogenesis" and "carbon fixation" are hypothesized to perform major functions in drought resistance in AtDREB1A -expressing transgenic plants. Furthermore, the number of DEGs associated with different transcription factors increased significantly after drought stress, especially the AP2/ERF, bZIP and MYB protein families. Taken together, this study substantially expands the transcriptomic information for S. miltiorrhiza and provides valuable clues for elucidating the mechanism of AtDREB1A-mediated drought tolerance in transgenic plants.

How Do People Become W.E.I.R.D.? Migration Reveals the Cultural Transmission Mechanisms Underlying Variation in Psychological Processes.

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Alex Mesoudi

Full Text Available Cultural psychologists have shown that people from Western, Educated, Industrialised, Rich, Democratic (WEIRD countries often exhibit different psychological processing to people from less-WEIRD countries. The former exhibit more individualistic and less collectivistic social orientation, and more analytic and less holistic cognition, than non-Westerners. Yet the mechanisms responsible for maintaining this cultural variation are unclear. Immigration is an ideal 'natural experiment' for uncovering such mechanisms. We used a battery of psychological measures previously shown to vary cross-culturally to compare the social orientation and cognitive style of 286 residents of East London from three cultural backgrounds: (i 1st-generation British Bangladeshi immigrants; (ii 2nd-generation British Bangladeshis raised in the UK to Bangladeshi-raised parents; and (iii non-migrants whose parents were born and raised in the UK. Model comparison revealed that individualism and dispositional attribution, typical of Western societies, are driven primarily by horizontal cultural transmission (e.g. via mass media, with parents and other family members having little or no effect, while collectivism, social closeness and situational attribution were driven by a mix of vertical/oblique cultural transmission (e.g. via family contact and horizontal cultural transmission. These individual-level transmission dynamics can explain hitherto puzzling population-level phenomena, such as the partial acculturation of 2nd-generation immigrants on measures such as collectivism (due to the mix of vertical and horizontal cultural transmission, or the observation in several countries of increasing individualism (which is transmitted horizontally and therefore rapidly despite little corresponding change in collectivism (which is transmitted partly vertically and therefore more slowly. Further consideration of cultural transmission mechanisms, in conjunction with the study of

How Do People Become W.E.I.R.D.? Migration Reveals the Cultural Transmission Mechanisms Underlying Variation in Psychological Processes.

Science.gov (United States)

Mesoudi, Alex; Magid, Kesson; Hussain, Delwar

2016-01-01

Cultural psychologists have shown that people from Western, Educated, Industrialised, Rich, Democratic (WEIRD) countries often exhibit different psychological processing to people from less-WEIRD countries. The former exhibit more individualistic and less collectivistic social orientation, and more analytic and less holistic cognition, than non-Westerners. Yet the mechanisms responsible for maintaining this cultural variation are unclear. Immigration is an ideal 'natural experiment' for uncovering such mechanisms. We used a battery of psychological measures previously shown to vary cross-culturally to compare the social orientation and cognitive style of 286 residents of East London from three cultural backgrounds: (i) 1st-generation British Bangladeshi immigrants; (ii) 2nd-generation British Bangladeshis raised in the UK to Bangladeshi-raised parents; and (iii) non-migrants whose parents were born and raised in the UK. Model comparison revealed that individualism and dispositional attribution, typical of Western societies, are driven primarily by horizontal cultural transmission (e.g. via mass media), with parents and other family members having little or no effect, while collectivism, social closeness and situational attribution were driven by a mix of vertical/oblique cultural transmission (e.g. via family contact) and horizontal cultural transmission. These individual-level transmission dynamics can explain hitherto puzzling population-level phenomena, such as the partial acculturation of 2nd-generation immigrants on measures such as collectivism (due to the mix of vertical and horizontal cultural transmission), or the observation in several countries of increasing individualism (which is transmitted horizontally and therefore rapidly) despite little corresponding change in collectivism (which is transmitted partly vertically and therefore more slowly). Further consideration of cultural transmission mechanisms, in conjunction with the study of migrant

How Do People Become W.E.I.R.D.? Migration Reveals the Cultural Transmission Mechanisms Underlying Variation in Psychological Processes

Science.gov (United States)

Mesoudi, Alex; Magid, Kesson; Hussain, Delwar

2016-01-01

Cultural psychologists have shown that people from Western, Educated, Industrialised, Rich, Democratic (WEIRD) countries often exhibit different psychological processing to people from less-WEIRD countries. The former exhibit more individualistic and less collectivistic social orientation, and more analytic and less holistic cognition, than non-Westerners. Yet the mechanisms responsible for maintaining this cultural variation are unclear. Immigration is an ideal ‘natural experiment’ for uncovering such mechanisms. We used a battery of psychological measures previously shown to vary cross-culturally to compare the social orientation and cognitive style of 286 residents of East London from three cultural backgrounds: (i) 1st-generation British Bangladeshi immigrants; (ii) 2nd-generation British Bangladeshis raised in the UK to Bangladeshi-raised parents; and (iii) non-migrants whose parents were born and raised in the UK. Model comparison revealed that individualism and dispositional attribution, typical of Western societies, are driven primarily by horizontal cultural transmission (e.g. via mass media), with parents and other family members having little or no effect, while collectivism, social closeness and situational attribution were driven by a mix of vertical/oblique cultural transmission (e.g. via family contact) and horizontal cultural transmission. These individual-level transmission dynamics can explain hitherto puzzling population-level phenomena, such as the partial acculturation of 2nd-generation immigrants on measures such as collectivism (due to the mix of vertical and horizontal cultural transmission), or the observation in several countries of increasing individualism (which is transmitted horizontally and therefore rapidly) despite little corresponding change in collectivism (which is transmitted partly vertically and therefore more slowly). Further consideration of cultural transmission mechanisms, in conjunction with the study of migrant

Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness.

Science.gov (United States)

Carroll, Joseph; Neitz, Maureen; Hofer, Heidi; Neitz, Jay; Williams, David R

2004-06-01

There is enormous variation in the X-linked L/M (long/middle wavelength sensitive) gene array underlying "normal" color vision in humans. This variability has been shown to underlie individual variation in color matching behavior. Recently, red-green color blindness has also been shown to be associated with distinctly different genotypes. This has opened the possibility that there may be important phenotypic differences within classically defined groups of color blind individuals. Here, adaptive optics retinal imaging has revealed a mechanism for producing dichromatic color vision in which the expression of a mutant cone photopigment gene leads to the loss of the entire corresponding class of cone photoreceptor cells. Previously, the theory that common forms of inherited color blindness could be caused by the loss of photoreceptor cells had been discounted. We confirm that remarkably, this loss of one-third of the cones does not impair any aspect of vision other than color.

Orchestrating Proactive and Reactive Mechanisms for Filtering Distracting Information: Brain-Behavior Relationships Revealed by a Mixed-Design fMRI Study

Science.gov (United States)

Marini, Francesco; Demeter, Elise; Roberts, Kenneth C.; Chelazzi, Leonardo

2016-01-01

Given the information overload often imparted to human cognitive-processing systems, suppression of irrelevant and distracting information is essential for successful behavior. Using a hybrid block/event-related fMRI design, we characterized proactive and reactive brain mechanisms for filtering distracting stimuli. Participants performed a flanker task, discriminating the direction of a target arrow in the presence versus absence of congruent or incongruent flanking distracting arrows during either Pure blocks (distracters always absent) or Mixed blocks (distracters on 80% of trials). Each Mixed block had either 20% or 60% incongruent trials. Activations in the dorsal frontoparietal attention network during Mixed versus Pure blocks evidenced proactive (blockwise) recruitment of a distraction-filtering mechanism. Sustained activations in right middle frontal gyrus during 60% Incongruent blocks correlated positively with behavioral indices of distraction-filtering (slowing when distracters might occur) and negatively with distraction-related behavioral costs (incongruent vs congruent trials), suggesting a role in coordinating proactive filtering of potential distracters. Event-related analyses showed that incongruent trials elicited greater reactive activations in 20% (vs 60%) Incongruent blocks for counteracting distraction and conflict, including in the insula and anterior cingulate. Context-related effects in occipitoparietal cortex consisted of greater target-evoked activations for distracter-absent trials (central-target-only) in Mixed versus Pure blocks, suggesting enhanced attentional engagement. Functional-localizer analyses in V1/V2/V3 revealed less distracter-processing activity in 60% (vs 20%) Incongruent blocks, presumably reflecting tonic suppression by proactive filtering mechanisms. These results delineate brain mechanisms underlying proactive and reactive filtering of distraction and conflict, and how they are orchestrated depending on distraction

Divided versus selective attention: evidence for common processing mechanisms.

Science.gov (United States)

Hahn, Britta; Wolkenberg, Frank A; Ross, Thomas J; Myers, Carol S; Heishman, Stephen J; Stein, Dan J; Kurup, Pradeep K; Stein, Elliot A

2008-06-18

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention.

Innovation and problem solving: a review of common mechanisms.

Science.gov (United States)

Griffin, Andrea S; Guez, David

2014-11-01

Behavioural innovations have become central to our thinking about how animals adjust to changing environments. It is now well established that animals vary in their ability to innovate, but understanding why remains a challenge. This is because innovations are rare, so studying innovation requires alternative experimental assays that create opportunities for animals to express their ability to invent new behaviours, or use pre-existing ones in new contexts. Problem solving of extractive foraging tasks has been put forward as a suitable experimental assay. We review the rapidly expanding literature on problem solving of extractive foraging tasks in order to better understand to what extent the processes underpinning problem solving, and the factors influencing problem solving, are in line with those predicted, and found, to underpin and influence innovation in the wild. Our aim is to determine whether problem solving can be used as an experimental proxy of innovation. We find that in most respects, problem solving is determined by the same underpinning mechanisms, and is influenced by the same factors, as those predicted to underpin, and to influence, innovation. We conclude that problem solving is a valid experimental assay for studying innovation, propose a conceptual model of problem solving in which motor diversity plays a more central role than has been considered to date, and provide recommendations for future research using problem solving to investigate innovation. This article is part of a Special Issue entitled: Cognition in the wild. Copyright © 2014 Elsevier B.V. All rights reserved.

Genes and (Common) Pathways Underlying Drug Addiction

Science.gov (United States)

Li, Chuan-Yun; Mao, Xizeng; Wei, Liping

2008-01-01

Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn), the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction. PMID:18179280

Genes and (common pathways underlying drug addiction.

Directory of Open Access Journals (Sweden)

Chuan-Yun Li

2008-01-01

Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

Applications in solid mechanics

DEFF Research Database (Denmark)

Ølgaard, Kristian Breum; Wells, Garth N.

2012-01-01

Problems in solid mechanics constitute perhaps the largest field of application of finite element methods. The vast majority of solid mechanics problems involve the standard momentum balance equation, posed in a Lagrangian setting, with different models distinguished by the choice of nonlinear...... or linearized kinematics, and the constitutive model for determining the stress. For some common models, the constitutive relationships are rather complex. This chapter addresses a number of canonical solid mechanics models in the context of automated modeling, and focuses on some pertinent issues that arise...

BAC and RNA sequencing reveal the brown planthopper resistance gene BPH15 in a recombination cold spot that mediates a unique defense mechanism.

Science.gov (United States)

Lv, Wentang; Du, Ba; Shangguan, Xinxin; Zhao, Yan; Pan, Yufang; Zhu, Lili; He, Yuqing; He, Guangcun

2014-08-11

Brown planthopper (BPH, Nilaparvata lugens Stål), is the most destructive phloem-feeding insect pest of rice (Oryza sativa). The BPH-resistance gene BPH15 has been proved to be effective in controlling the pest and widely applied in rice breeding programs. Nevertheless, molecular mechanism of the resistance remain unclear. In this study, we narrowed down the position of BPH15 on chromosome 4 and investigated the transcriptome of BPH15 rice after BPH attacked. We analyzed 13,000 BC2F2 plants of cross between susceptible rice TN1 and the recombinant inbred line RI93 that carrying the BPH15 gene from original resistant donor B5. BPH15 was mapped to a 0.0269 cM region on chromosome 4, which is 210-kb in the reference genome of Nipponbare. Sequencing bacterial artificial chromosome (BAC) clones that span the BPH15 region revealed that the physical size of BPH15 region in resistant rice B5 is 580-kb, much bigger than the corresponding region in the reference genome of Nipponbare. There were 87 predicted genes in the BPH15 region in resistant rice. The expression profiles of predicted genes were analyzed. Four jacalin-related lectin proteins genes and one LRR protein gene were found constitutively expressed in resistant parent and considered the candidate genes of BPH15. The transcriptomes of resistant BPH15 introgression line and the susceptible recipient line were analyzed using high-throughput RNA sequencing. In total, 2,914 differentially expressed genes (DEGs) were identified. BPH-responsive transcript profiles were distinct between resistant and susceptible plants and between the early stage (6 h after infestation, HAI) and late stage (48 HAI). The key defense mechanism was related to jasmonate signaling, ethylene signaling, receptor kinase, MAPK cascades, Ca(2+) signaling, PR genes, transcription factors, and protein posttranslational modifications. Our work combined BAC and RNA sequencing to identify candidate genes of BPH15 and revealed the resistance mechanism

Are there common mechanisms in sensation seeking and reality distortion in schizophrenia? A study using memory event-related potentials.

Science.gov (United States)

Guillem, François; Pampoulova, Tania; Stip, Emmanuel; Todorov, Christo; Lalonde, Pierre

2005-05-15

A growing literature suggests that the characteristics of sensation seeking and reality distortion expressed in schizophrenia share several mechanisms. In a previous study, the comparison of patients with high vs. low reality distortion using event-related potentials (ERPs) recorded in a recognition memory task for unfamiliar faces identified neural and cognitive anomalies specifically related to the expression of these symptoms. As a follow-up, this study investigated the ERP correlates of sensation seeking in schizophrenia using the same recognition memory protocol. ERPs have been recorded in controls (N=21) and schizophrenia patients separated into high (HSS; N=13) and low (LSS; N=17) scorers according to Zuckerman's Sensation Seeking Scale. The results show a reduced P2a that was found unrelated to reality distortion in the previous study of reality distortion. It identifies interference inhibition impairment as being specifically related to sensation seeking. On the other hand, HSS scorers display enhanced fronto-central and normal P600 effects also found in high reality distortion patients. These results indicate inappropriate context processing and mnemonic binding common to sensation seeking and reality distortion. LSS scorers also display a reduced temporal N300 similar to that found in low reality distortion patients. This anomaly could reflect the lower reactivity to emotionally significant stimuli that underlies anhedonia symptoms. Finally, the N400 effect and a late frontal effect are found in both HSS and LSS. Since they were unrelated to reality distortion, these indices have been related to basic aspects of schizophrenia, e.g., deficient knowledge integration, or other mechanisms, e.g. anxiety or impulsivity. In summary, the present study examines the strategy of investigating variables, such as temperamental characteristics, in addition to symptoms, to show how discrete impairments may contribute to the expression of the illness.

Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

Directory of Open Access Journals (Sweden)

Xianxin Li

Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

Quantum mechanics. An epistemological revolution that is revealed in the description of micro-states

International Nuclear Information System (INIS)

Mugur-Schachter, M.

2009-01-01

The author deals with the issue of why quantum mechanics is so difficult to understand. The answer is identified here: the quantum formalism includes the principles of a radical revolution in epistemology. The development of these principles has led to an entire re-shaping of how to generate knowledge in sciences. It is a description of what lays behind quantum mechanics in terms of conceptualization. (A.C.)

Common Fluorescence In Situ Hybridization Applications in Cytology.

Science.gov (United States)

Savic, Spasenija; Bubendorf, Lukas

2016-12-01

- Fluorescence in situ hybridization (FISH) is a well-established method for detection of genomic aberrations in diagnostic, prognostic, and predictive marker testing. - To review common applications of FISH in cytology. - The published literature was reviewed. - Cytology is particularly well suited for all kinds of FISH applications, which is highlighted in respiratory tract cytology with an increasing demand for predictive FISH testing in lung cancer. Fluorescence in situ hybridization is the gold standard for detection of predictive anaplastic lymphoma kinase gene (ALK) rearrangements, and the same evaluation criteria as in histology apply to cytology. Several other gene rearrangements, including ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), are becoming clinically important and share the same underlining cytogenetic mechanisms with ALK. MET amplification is one of the most common mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and can be targeted by crizotinib. As genomic aberrations are a hallmark of malignant cells, FISH is a valuable objective ancillary diagnostic tool. In urinary tract cytology, atypical urothelial cells equivocal for malignancy are a common diagnostic dilemma and multitarget FISH can help clarify such cells. Diagnosis of malignant mesothelioma remains one of the most challenging fields in effusion cytology, and ancillary FISH is useful in establishing the diagnosis. Fluorescence in situ hybridization is a morphology-based technique, and the prerequisite for reliable FISH results is a targeted evaluation of the cells in question (eg, cancer or atypical cells). Cytopathologists and cytotechnicians should therefore be involved in molecular testing in order to select the best material and to provide their morphologic expertise.

MUS81 promotes common fragile site expression

DEFF Research Database (Denmark)

Ying, Songmin; Minocherhomji, Sheroy; Chan, Kok Lung

2013-01-01

Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the fait......Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair...... the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early...

Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology.

Science.gov (United States)

Port, Russell G; Gandal, Michael J; Roberts, Timothy P L; Siegel, Steven J; Carlson, Gregory C

2014-01-01

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Convergence of Circuit Dysfunction in ASD: A common bridge between diverse genetic and environmental risk factors and common clinical neurophysiology.

Directory of Open Access Journals (Sweden)

Russell G Port

2014-12-01

Full Text Available Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD. Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents. Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in-vivo and ex-vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Convergence of circuit dysfunction in ASD: a common bridge between diverse genetic and environmental risk factors and common clinical electrophysiology

Science.gov (United States)

Port, Russell G.; Gandal, Michael J.; Roberts, Timothy P. L.; Siegel, Steven J.; Carlson, Gregory C.

2014-01-01

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD. PMID:25538564

Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

Directory of Open Access Journals (Sweden)

Karin Voordeckers

2015-11-01

Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

Science.gov (United States)

Zhou, Li; Todorovic, Viktor; Kakavas, Steve; Sielaff, Bernhard; Medina, Limary; Wang, Leyu; Sadhukhan, Ramkrishna; Stockmann, Henning; Richardson, Paul L; DiGiammarino, Enrico; Sun, Chaohong; Scott, Victoria

2018-01-12

IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36β, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 μm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Transcriptome analysis of two recombinant inbred lines of common bean contrasting for symbiotic nitrogen fixation

Science.gov (United States)

Common bean (Phaseolus vulgaris L.) is able to fix atmospheric nitrogen (N2) through symbiotic nitrogen fixation (SNF). Effective utilization of existing variability for SNF in common bean for genetic improvement requires an understanding of underlying genes and molecular mechanisms. The utility of ...

Mechanisms of behavior modification in clinical behavioral medicine in China.

Science.gov (United States)

Yang, Zhiyin; Su, Zhonghua; Ji, Feng; Zhu, Min; Bai, Bo

2014-08-01

Behavior modification, as the core of clinical behavioral medicine, is often used in clinical settings. We seek to summarize behavior modification techniques that are commonly used in clinical practice of behavioral medicine in China and discuss possible biobehavioral mechanisms. We reviewed common behavior modification techniques in clinical settings in China, and we reviewed studies that explored possible biobehavioral mechanisms. Commonly used clinical approaches of behavior modification in China include behavior therapy, cognitive therapy, cognitive-behavioral therapy, health education, behavior management, behavioral relaxation training, stress management intervention, desensitization therapy, biofeedback therapy, and music therapy. These techniques have been applied in the clinical treatment of a variety of diseases, such as chronic diseases, psychosomatic diseases, and psychological disorders. The biobehavioral mechanisms of these techniques involve the autonomic nervous system, neuroendocrine system, neurobiochemistry, and neuroplasticity. Behavior modification techniques are commonly used in the treatment of a variety of somatic and psychological disorders in China. Multiple biobehavioral mechanisms are involved in successful behavior modification.

Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

Science.gov (United States)

Turner, Leslie M; Harr, Bettina

2014-12-09

Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

Science.gov (United States)

Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

2018-05-04

Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

Revealing strong bias in common measures of galaxy properties using new inclination-independent structures

Science.gov (United States)

Devour, Brian M.; Bell, Eric F.

2017-06-01

Accurate measurement of galaxy structures is a prerequisite for quantitative investigation of galaxy properties or evolution. Yet, the impact of galaxy inclination and dust on commonly used metrics of galaxy structure is poorly quantified. We use infrared data sets to select inclination-independent samples of disc and flattened elliptical galaxies. These samples show strong variation in Sérsic index, concentration and half-light radii with inclination. We develop novel inclination-independent galaxy structures by collapsing the light distribution in the near-infrared on to the major axis, yielding inclination-independent 'linear' measures of size and concentration. With these new metrics we select a sample of Milky Way analogue galaxies with similar stellar masses, star formation rates, sizes and concentrations. Optical luminosities, light distributions and spectral properties are all found to vary strongly with inclination: When inclining to edge-on, r-band luminosities dim by >1 magnitude, sizes decrease by a factor of 2, 'dust-corrected' estimates of star formation rate drop threefold, metallicities decrease by 0.1 dex and edge-on galaxies are half as likely to be classified as star forming. These systematic effects should be accounted for in analyses of galaxy properties.

Genetic and biochemical evidences reveal novel insights into the ...

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences; Volume 41; Issue 4. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. INDRAJEET GHODKE K MUNIYAPPA. ARTICLE Volume 41 Issue 4 December 2016 pp ...

Evaluation of chemical and/or mechanical treatments of the smear layer as revealed by scanning electron microscopy - a blind comparative study

Directory of Open Access Journals (Sweden)

LUZ Maria Aparecida Alves de Cerqueira

2000-01-01

Full Text Available A blind comparative study of chemical and/or mechanical treatments of the smear layer, according to scanning electron microscopy images, was carried out. The effect of the treatments was analyzed on the smear layer of mesio-occlusodistal cavity walls prepared in vitro in human third molars. The agents used were air/water spray, 37% phosphoric acid, 5% tannic acid, biologic detergent, 0.5% sodium hypochlorite, and enamel hatchet alone or in association with the previous agents. Electron micrographs were evaluated by three professionals according to the degree of visualization of underlying dentin or enamel. Phosphoric acid received the highest scores due to the complete removal of the smear layer. However, statistical analyses revealed diverse performances of non or slightly demineralizing agents, according to the cavity walls in dentin, while there was equivalent effect on the enamel of gingival walls.

Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.

Science.gov (United States)

Dieterich, Christine; Puey, Angela; Lin, Sylvia; Lyn, Sylvia; Swezey, Robert; Furimsky, Anna; Fairchild, David; Mirsalis, Jon C; Ng, Hanna H

2009-01-01

Vancomycin, one of few effective treatments against methicillin-resistant Staphylococcus aureus, is nephrotoxic. The goals of this study were to (1) gain insights into molecular mechanisms of nephrotoxicity at the genomic level, (2) evaluate gene markers of vancomycin-induced kidney injury, and (3) compare gene expression responses after iv and ip administration. Groups of six female BALB/c mice were treated with seven daily iv or ip doses of vancomycin (50, 200, and 400 mg/kg) or saline, and sacrificed on day 8. Clinical chemistry and histopathology demonstrated kidney injury at 400 mg/kg only. Hierarchical clustering analysis revealed that kidney gene expression profiles of all mice treated at 400 mg/kg clustered with those of mice administered 200 mg/kg iv. Transcriptional profiling might thus be more sensitive than current clinical markers for detecting kidney damage, though the profiles can differ with the route of administration. Analysis of transcripts whose expression was changed by at least twofold compared with vehicle saline after high iv and ip doses of vancomycin suggested the possibility of oxidative stress and mitochondrial damage in vancomycin-induced toxicity. In addition, our data showed changes in expression of several transcripts from the complement and inflammatory pathways. Such expression changes were confirmed by relative real-time reverse transcription-polymerase chain reaction. Finally, our results further substantiate the use of gene markers of kidney toxicity such as KIM-1/Havcr1, as indicators of renal injury.

Common rugby league injuries. Recommendations for treatment and preventative measures.

Science.gov (United States)

Gibbs, N

1994-12-01

Rugby league is the main professional team sport played in Eastern Australia. It is also very popular at a junior and amateur level. However, injuries are common because of the amount of body contact that occurs and the amount of running that is required to participate in the game. Injuries to the lower limbs account for over 50% of all injuries. The most common specific injuries are ankle lateral ligament tears, knee medial collateral and anterior cruciate ligament tears, groin musculotendinous tears, hamstring and calf muscle tears, and quadriceps muscle contusions. Head injuries are common and consist of varying degrees of concussion as well as lacerations and facial fractures. Serious head injury is rare. Some of the more common upper limb injuries are to the acromioclavicular and glenohumeral joints. Accurate diagnosis of these common injuries using appropriate history, examination and investigations is critical in organising a treatment and rehabilitation plan that will return the player to competition as soon as possible. An understanding of the mechanism of injury is also important in order to develop preventative strategies.

Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

Science.gov (United States)

Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

2016-02-01

Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

Shared genetic variants suggest common pathways in allergy and autoimmune diseases

DEFF Research Database (Denmark)

Kreiner-Møller, Eskil; Waage, Johannes; Standl, Marie

2017-01-01

Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed two GWAS on self-r...

Are common symbiosis genes required for endophytic rice-rhizobial interactions?

Science.gov (United States)

Chen, Caiyan; Zhu, Hongyan

2013-09-01

Legume plants are able to establish root nodule symbioses with nitrogen-fixing bacteria, called rhizobia. Recent studies revealed that the root nodule symbiosis has co-opted the signaling pathway that mediates the ancestral mycorrhizal symbiosis that occurs in most land plants. Despite being unable to induce nodulation, rhizobia have been shown to be able to infect and colonize the roots of non-legumes such as rice. One fascinating question is whether establishment of such associations requires the common symbiosis (Sym) genes that are essential for infection of plant cells by mycorrhizal fungi and rhizobia in legumes. Here, we demonstrated that the common Sym genes are not required for endophytic colonization of rice roots by nitrogen-fixing rhizobia.

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

International Nuclear Information System (INIS)

Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

2014-01-01

The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology

Rheology of transgenic switchgrass reveals practical aspects of biomass processing.

Science.gov (United States)

Wan, Guigui; Frazier, Taylor; Jorgensen, Julianne; Zhao, Bingyu; Frazier, Charles E

2018-01-01

Mechanical properties of transgenic switchgrass have practical implications for biorefinery technologies. Presented are fundamentals for simple (thermo)mechanical measurements of genetically transformed switchgrass. Experimental basics are provided for the novice, where the intention is to promote collaboration between plant biologists and materials scientists. Stem sections were subjected to two stress modes: (1) torsional oscillation in the linear response region, and (2) unidirectional torsion to failure. Specimens were analyzed while submerged/saturated in ethylene glycol, simulating natural hydration and allowing experimental temperatures above 100 °C for an improved view of the lignin glass transition. Down-regulation of the 4-Coumarate:coenzyme A ligase gene (reduced lignin content and altered monomer composition) generally resulted in less stiff and weaker stems. These observations were associated with a reduction in the temperature and activation energy of the lignin glass transition, but surprisingly with no difference in the breadth and intensity of the tan  δ signal. The results showed promise in further investigations of how rheological methods relate to stem lignin content, composition, and functional properties in the field and in bioprocessing. Measurements such as these are complicated by small specimen size; however, torsional rheometers (relatively common in polymer laboratories) are well suited for this task. As opposed to the expense and complication of relative humidity control, solvent-submersion rheological methods effectively reveal fundamental structure/property relationships in plant tissues. Demonstrated are low-strain linear methods, and also nonlinear yield and failure analysis; the latter is very uncommon for typical rheological equipment.

Biospectroscopy reveals the effect of varying water quality on tadpole tissues of the common frog (Rana temporaria)

OpenAIRE

Strong, Becky; Halsall, Crispin James; Ferenčík, Martin; Jones, Kevin Christopher; Shore, Richard Francis; Martin, Francis Luke

2016-01-01

Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog (Rana temporaria) tadpol...

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

Science.gov (United States)

Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

2013-01-01

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

Aberrant ovarian artery arising from the common Iliac artery: Case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Won Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Yang, Seung Boo; Lee, Jae Myeong [Dept. of Radiology, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi (Korea, Republic of); Goo, Dong Erk; Kim, Yong Jae; Chang, Yun Woo [Dept. of Radiology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul (Korea, Republic of)

2013-01-15

A 46-year-old Vietnamese woman received embolization therapy in order to control postpartum hemorrhage. Angiography revealed an aberrant ovarian artery arising from the right common iliac artery. Superselective catheterization and subsequent embolization of the aberrant ovarian artery and bilateral uterine arteries were performed. Precise knowledge of the anatomic variations of the ovarian artery is important for successful embolization.

Aberrant ovarian artery arising from the common Iliac artery: Case report

International Nuclear Information System (INIS)

Kim, Won Kyung; Yang, Seung Boo; Lee, Jae Myeong; Goo, Dong Erk; Kim, Yong Jae; Chang, Yun Woo

2013-01-01

A 46-year-old Vietnamese woman received embolization therapy in order to control postpartum hemorrhage. Angiography revealed an aberrant ovarian artery arising from the right common iliac artery. Superselective catheterization and subsequent embolization of the aberrant ovarian artery and bilateral uterine arteries were performed. Precise knowledge of the anatomic variations of the ovarian artery is important for successful embolization.

EPR-technical codes - a common basis for the EPR

International Nuclear Information System (INIS)

Zaiss, W.; Appell, B.

1997-01-01

The design and construction of Nuclear Power Plants implies a full set of codes and standards to define the construction rules of components and equipment. Rules are existing and are currently implemented, respectively in France and Germany (mainly RCCs and KTA safety standards). In the frame of the EPR-project, the common objective requires an essential industrial work programme between engineers from both countries to elaborate a common set of codes and regulations. These new industrial rules are called the ETCs (EPR Technical Codes). In the hierarchy the ETCs are - in case of France - on the common level of basic safety rules (RFS), design and construction rules (RCC) and - in Germany - belonging to RSK guidelines and KTA safety standards. A set of six ETCs will be elaborated to cover: safety and process, mechanical components, electrical equipment, instrumentation and control, civil works, fire protection. (orig.)

Characterization of the anisotropic mechanical behavior of human abdominal wall connective tissues.

Science.gov (United States)

Astruc, Laure; De Meulaere, Maurice; Witz, Jean-François; Nováček, Vit; Turquier, Frédéric; Hoc, Thierry; Brieu, Mathias

2018-06-01

Abdominal wall sheathing tissues are commonly involved in hernia formation. However, there is very limited work studying mechanics of all tissues from the same donor which prevents a complete understanding of the abdominal wall behavior and the differences in these tissues. The aim of this study was to investigate the differences between the mechanical properties of the linea alba and the anterior and posterior rectus sheaths from a macroscopic point of view. Eight full-thickness human anterior abdominal walls of both genders were collected and longitudinal and transverse samples were harvested from the three sheathing connective tissues. The total of 398 uniaxial tensile tests was conducted and the mechanical characteristics of the behavior (tangent rigidities for small and large deformations) were determined. Statistical comparisons highlighted heterogeneity and non-linearity in behavior of the three tissues under both small and large deformations. High anisotropy was observed under small and large deformations with higher stress in the transverse direction. Variabilities in the mechanical properties of the linea alba according to the gender and location were also identified. Finally, data dispersion correlated with microstructure revealed that macroscopic characterization is not sufficient to fully describe behavior. Microstructure consideration is needed. These results provide a better understanding of the mechanical behavior of the abdominal wall sheathing tissues as well as the directions for microstructure-based constitutive model. Copyright © 2018 Elsevier Ltd. All rights reserved.

In situ observations of the atomistic mechanisms of Ni catalyzed low temperature graphene growth.

Science.gov (United States)

Patera, Laerte L; Africh, Cristina; Weatherup, Robert S; Blume, Raoul; Bhardwaj, Sunil; Castellarin-Cudia, Carla; Knop-Gericke, Axel; Schloegl, Robert; Comelli, Giovanni; Hofmann, Stephan; Cepek, Cinzia

2013-09-24

The key atomistic mechanisms of graphene formation on Ni for technologically relevant hydrocarbon exposures below 600 °C are directly revealed via complementary in situ scanning tunneling microscopy and X-ray photoelectron spectroscopy. For clean Ni(111) below 500 °C, two different surface carbide (Ni2C) conversion mechanisms are dominant which both yield epitaxial graphene, whereas above 500 °C, graphene predominantly grows directly on Ni(111) via replacement mechanisms leading to embedded epitaxial and/or rotated graphene domains. Upon cooling, additional carbon structures form exclusively underneath rotated graphene domains. The dominant graphene growth mechanism also critically depends on the near-surface carbon concentration and hence is intimately linked to the full history of the catalyst and all possible sources of contamination. The detailed XPS fingerprinting of these processes allows a direct link to high pressure XPS measurements of a wide range of growth conditions, including polycrystalline Ni catalysts and recipes commonly used in industrial reactors for graphene and carbon nanotube CVD. This enables an unambiguous and consistent interpretation of prior literature and an assessment of how the quality/structure of as-grown carbon nanostructures relates to the growth modes.

Immune Mechanisms in Myelodysplastic Syndrome

DEFF Research Database (Denmark)

Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

2016-01-01

diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

Synchronization as a biological, psychological and social mechanism to create common time: A theoretical frame and a single case study.

Science.gov (United States)

Bao, Yan; Pöppel, Ernst; Wang, Lingyan; Lin, Xiaoxiong; Yang, Taoxi; Avram, Mihai; Blautzik, Janusch; Paolini, Marco; Silveira, Sarita; Vedder, Aline; Zaytseva, Yuliya; Zhou, Bin

2015-12-01

Synchronizing neural processes, mental activities, and social interactions is considered to be fundamental for the creation of temporal order on the personal and interpersonal level. Several different types of synchronization are distinguished, and for each of them examples are given: self-organized synchronizations on the neural level giving rise to pre-semantically defined time windows of some tens of milliseconds and of approximately 3 s; time windows that are created by synchronizing different neural representations, as for instance in aesthetic appreciations or moral judgments; and synchronization of biological rhythms with geophysical cycles, like the circadian clock with the 24-hr rhythm of day and night. For the latter type of synchronization, an experiment is described that shows the importance of social interactions for sharing or avoiding common time. In a group study with four subjects being completely isolated together for 3 weeks from the external world, social interactions resulted both in intra- and interindividual circadian synchronization and desynchronization. A unique phenomenon in circadian regulation is described, the "beat phenomenon," which has been made visible by the interaction of two circadian rhythms with different frequencies in one body. The separation of the two physiological rhythms was the consequence of social interactions, that is, by the desire of a subject to share and to escape common time during different phases of the long-term experiment. The theoretical arguments on synchronization are summarized with the general statement: "Nothing in cognitive science makes sense except in the light of time windows." The hypothesis is forwarded that time windows that express discrete timing mechanisms in behavioral control and on the level of conscious experiences are the necessary bases to create cognitive order, and it is suggested that time windows are implemented by neural oscillations in different frequency domains. © 2015 The

Gender identity disorder and schizophrenia: neurodevelopmental disorders with common causal mechanisms?

Science.gov (United States)

Rajkumar, Ravi Philip

2014-01-01

Gender identity disorder (GID), recently renamed gender dysphoria (GD), is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF), early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.

Gender Identity Disorder and Schizophrenia: Neurodevelopmental Disorders with Common Causal Mechanisms?

Directory of Open Access Journals (Sweden)

Ravi Philip Rajkumar

2014-01-01

Full Text Available Gender identity disorder (GID, recently renamed gender dysphoria (GD, is a rare condition characterized by an incongruity between gender identity and biological sex. Clinical evidence suggests that schizophrenia occurs in patients with GID at rates higher than in the general population and that patients with GID may have schizophrenia-like personality traits. Conversely, patients with schizophrenia may experience alterations in gender identity and gender role perception. Neurobiological research, including brain imaging and studies of finger length ratio and handedness, suggests that both these disorders are associated with altered cerebral sexual dimorphism and changes in cerebral lateralization. Various mechanisms, such as Toxoplasma infection, reduced levels of brain-derived neurotrophic factor (BDNF, early childhood adversity, and links with autism spectrum disorders, may account for some of this overlap. The implications of this association for further research are discussed.

Genes and co-expression modules common to drought and bacterial stress responses in Arabidopsis and rice.

Directory of Open Access Journals (Sweden)

Rafi Shaik

Full Text Available Plants are simultaneously exposed to multiple stresses resulting in enormous changes in the molecular landscape within the cell. Identification and characterization of the synergistic and antagonistic components of stress response mechanisms contributing to the cross talk between stresses is of high priority to explore and enhance multiple stress responses. To this end, we performed meta-analysis of drought (abiotic, bacterial (biotic stress response in rice and Arabidopsis by analyzing a total of 386 microarray samples belonging to 20 microarray studies and identified approximately 3100 and 900 DEGs in rice and Arabidopsis, respectively. About 38.5% (1214 and 28.7% (272 DEGs were common to drought and bacterial stresses in rice and Arabidopsis, respectively. A majority of these common DEGs showed conserved expression status in both stresses. Gene ontology enrichment analysis clearly demarcated the response and regulation of various plant hormones and related biological processes. Fatty acid metabolism and biosynthesis of alkaloids were upregulated and, nitrogen metabolism and photosynthesis was downregulated in both stress conditions. WRKY transcription family genes were highly enriched in all upregulated gene sets while 'CO-like' TF family showed inverse relationship of expression between drought and bacterial stresses. Weighted gene co-expression network analysis divided DEG sets into multiple modules that show high co-expression and identified stress specific hub genes with high connectivity. Detection of consensus modules based on DEGs common to drought and bacterial stress revealed 9 and 4 modules in rice and Arabidopsis, respectively, with conserved and reversed co-expression patterns.

Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network.

Science.gov (United States)

Le Merrer, Julie; Befort, Katia; Gardon, Olivier; Filliol, Dominique; Darcq, Emmanuel; Dembele, Doulaye; Becker, Jerome A J; Kieffer, Brigitte L

2012-01-01

Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology of drug abstinence, however, is poorly understood. We previously identified a unique set of hundred mu-opioid receptor-dependent genes in the extended amygdala, a key site for hedonic and stress processing in the brain. Here we examined these candidate genes either immediately after chronic morphine, nicotine, Δ9-tetrahydrocannabinol or alcohol, or following 4 weeks of abstinence. Regulation patterns strongly differed among chronic groups. In contrast, gene regulations strikingly converged in the abstinent groups and revealed unforeseen common adaptations within a novel huntingtin-centered molecular network previously unreported in addiction research. This study demonstrates that, regardless the drug, a specific set of transcriptional regulations develops in the abstinent brain, which possibly contributes to the negative affect characterizing protracted abstinence. This transcriptional signature may represent a hallmark of drug abstinence and a unitary adaptive molecular mechanism in substance abuse disorders. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations.

Directory of Open Access Journals (Sweden)

Jackson Champer

2017-07-01

Full Text Available A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, which works by converting cells that are heterozygous for the drive construct into homozygotes, thereby enabling super-Mendelian inheritance. Although CRISPR gene drive activity has already been demonstrated, a key obstacle for current systems is their propensity to generate resistance alleles, which cannot be converted to drive alleles. In this study, we developed two CRISPR gene drive constructs based on the nanos and vasa promoters that allowed us to illuminate the different mechanisms by which resistance alleles are formed in the model organism Drosophila melanogaster. We observed resistance allele formation at high rates both prior to fertilization in the germline and post-fertilization in the embryo due to maternally deposited Cas9. Assessment of drive activity in genetically diverse backgrounds further revealed substantial differences in conversion efficiency and resistance rates. Our results demonstrate that the evolution of resistance will likely impose a severe limitation to the effectiveness of current CRISPR gene drive approaches, especially when applied to diverse natural populations.

Commonness of Amazonian palm (Arecaceae) species: Cross-scale links and potential determinants

DEFF Research Database (Denmark)

Kristiansen, Thea; Svenning, J.-C.; Grández, César

2009-01-01

was positively related to topographic niche breadth. Stem height correlated with continental range size and was the only species life-history trait related to any commonness measure. Distance from the study area to a species' range centre did not influence any of the commonness measures. The factors determining......The mechanisms that cause variation in commonness (abundances and range sizes) of species remain debated in ecology, and a repeatedly observed pattern is the positive relation between local abundances and larger scale range sizes. We used the Amazonian palm species (Arecaceae) to investigate...... the dependence between and potential determinants of commonness across three (local, landscape, continental) spatial scales. Commonness at the smaller scales (local abundance, landscape frequency) was estimated using data from 57 transects (5 × 500 m) in primary, non-inundated (terra firme) rainforest...

Selective spider toxins reveal a role for Nav1.1 channel in mechanical pain

Science.gov (United States)

Osteen, Jeremiah D.; Herzig, Volker; Gilchrist, John; Emrick, Joshua J.; Zhang, Chuchu; Wang, Xidao; Castro, Joel; Garcia-Caraballo, Sonia; Grundy, Luke; Rychkov, Grigori Y.; Weyer, Andy D.; Dekan, Zoltan; Undheim, Eivind A. B.; Alewood, Paul; Stucky, Cheryl L.; Brierley, Stuart M.; Basbaum, Allan I.; Bosmans, Frank; King, Glenn F.; Julius, David

2016-01-01

Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibers of the pain pathway. Local anesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes and their contributions to chemical, mechanical, or thermal pain. Here, we identify and characterize spider toxins that selectively activate the Nav1.1 subtype, whose role in nociception and pain has not been explored. We exploit these probes to demonstrate that Nav1.1-expressing fibers are modality-specific nociceptors: their activation elicits robust pain behaviors without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibers also express Nav1.1 and show enhanced toxin sensitivity in a model of irritable bowel syndrome. Altogether, these findings establish an unexpected role for Nav1.1 in regulating the excitability of sensory nerve fibers that underlie mechanical pain. PMID:27281198

Disorders of compulsivity: a common bias towards learning habits.

Science.gov (United States)

Voon, V; Derbyshire, K; Rück, C; Irvine, M A; Worbe, Y; Enander, J; Schreiber, L R N; Gillan, C; Fineberg, N A; Sahakian, B J; Robbins, T W; Harrison, N A; Wood, J; Daw, N D; Dayan, P; Grant, J E; Bullmore, E T

2015-03-01

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.

Finding Common Ground: Identifying and Eliciting Metacognition in ePortfolios across Contexts

Science.gov (United States)

Bokser, Julie A.; Brown, Sarah; Chaden, Caryn; Moore, Michael; Cleary, Michelle Navarre; Reed, Susan; Seifert, Eileen; Zecker, Liliana Barro; Wozniak, Kathryn

2016-01-01

Research has suggested ePortfolios reveal and support students' metacognition, that is, their awareness, tracking, and evaluation of their learning over time. However, due to the wide variety of purposes and audiences for ePortfolios, it has been unclear whether there might be common criteria for identifying and assessing metacognition in…

How mechanical context and feedback jointly determine the use of mechanical variables in length perception by dynamic touch

NARCIS (Netherlands)

Menger, Rudmer; Withagen, Rob

Earlier studies have revealed that both mechanical context and feedback determine what mechanical invariant is used to perceive length by dynamic touch. In the present article, the authors examined how these two factors jointly constrain the informational variable that is relied upon. Participants

How mechanical context and feedback jointly determine the use of mechanical variables in length perception by dynamic touch

NARCIS (Netherlands)

Menger, Rudmer; Withagen, Rob

2009-01-01

Earlier studies have revealed that both mechanical context and feedback determine what mechanical invariant is used to perceive length by dynamic touch. In the present article, the authors examined how these two factors jointly constrain the informational variable that is relied upon. Participants

Common carp disrupt ecosystem structure and function through middle-out effects

Science.gov (United States)

Kaemingk, Mark A.; Jolley, Jeffrey C.; Paukert, Craig P.; Willis, David W.; Henderson, Kjetil R.; Holland, Richard S.; Wanner, Greg A.; Lindvall, Mark L.

2016-01-01

Middle-out effects or a combination of top-down and bottom-up processes create many theoretical and empirical challenges in the realm of trophic ecology. We propose using specific autecology or species trait (i.e. behavioural) information to help explain and understand trophic dynamics that may involve complicated and non-unidirectional trophic interactions. The common carp (Cyprinus carpio) served as our model species for whole-lake observational and experimental studies; four trophic levels were measured to assess common carp-mediated middle-out effects across multiple lakes. We hypothesised that common carp could influence aquatic ecosystems through multiple pathways (i.e. abiotic and biotic foraging, early life feeding, nutrient). Both studies revealed most trophic levels were affected by common carp, highlighting strong middle-out effects likely caused by common carp foraging activities and abiotic influence (i.e. sediment resuspension). The loss of water transparency, submersed vegetation and a shift in zooplankton dynamics were the strongest effects. Trophic levels furthest from direct pathway effects were also affected (fish life history traits). The present study demonstrates that common carp can exert substantial effects on ecosystem structure and function. Species capable of middle-out effects can greatly modify communities through a variety of available pathways and are not confined to traditional top-down or bottom-up processes.

fMRI reveals reciprocal inhibition between social and physical cognitive domains

Science.gov (United States)

Jack, Anthony I.; Dawson, Abigail; Begany, Katelyn; Leckie, Regina L.; Barry, Kevin; Ciccia, Angela; Snyder, Abraham

2012-01-01

Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which is directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results indicate

fMRI reveals reciprocal inhibition between social and physical cognitive domains.

Science.gov (United States)

Jack, Anthony I; Dawson, Abigail J; Begany, Katelyn L; Leckie, Regina L; Barry, Kevin P; Ciccia, Angela H; Snyder, Abraham Z

2013-02-01

Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which may be directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results

Classical and atypical agonists activate M1 muscarinic acetylcholine receptors through common mechanisms

Czech Academy of Sciences Publication Activity Database

Randáková, Alena; Dolejší, Eva; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; El-Fakahany, E. E.; Jakubík, Jan

2015-01-01

Roč. 97, Jul 2015 (2015), s. 27-39 ISSN 1043-6618 R&D Projects: GA ČR(CZ) GA305/09/0681; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) EE2.3.30.0025 Institutional support: RVO:67985823 Keywords : muscarinic acetylcholine receptors * atypical agonists * xanomeline * activation mechanism Subject RIV: ED - Physiology Impact factor: 4.816, year: 2015

Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's Aβ peptide

International Nuclear Information System (INIS)

Garvey, Megan; Tepper, Katharina; Haupt, Caroline; Knuepfer, Uwe; Klement, Karolin; Meinhardt, Jessica; Horn, Uwe; Balbach, Jochen; Faendrich, Marcus

2011-01-01

Highlights: → Sodium phosphate buffer accelerated Aβ(1-40) nucleation relative to HEPES. → Aβ(1-40) fibrils formed in the two buffers show only minor structural differences. → NMR revealed that Aβ(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of Aβ peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of Aβ and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of Aβ peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of Aβ fibrillation. The three histidine residues at positions 6, 13 and 14 of Aβ(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems

Science.gov (United States)

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α -uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α =2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c =e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c =1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α ≥3 , minimum vertex covers on α -uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c =e /(α -1 ) where the replica symmetry is broken.

Statistical mechanical analysis of linear programming relaxation for combinatorial optimization problems.

Science.gov (United States)

Takabe, Satoshi; Hukushima, Koji

2016-05-01

Typical behavior of the linear programming (LP) problem is studied as a relaxation of the minimum vertex cover (min-VC), a type of integer programming (IP) problem. A lattice-gas model on the Erdös-Rényi random graphs of α-uniform hyperedges is proposed to express both the LP and IP problems of the min-VC in the common statistical mechanical model with a one-parameter family. Statistical mechanical analyses reveal for α=2 that the LP optimal solution is typically equal to that given by the IP below the critical average degree c=e in the thermodynamic limit. The critical threshold for good accuracy of the relaxation extends the mathematical result c=1 and coincides with the replica symmetry-breaking threshold of the IP. The LP relaxation for the minimum hitting sets with α≥3, minimum vertex covers on α-uniform random graphs, is also studied. Analytic and numerical results strongly suggest that the LP relaxation fails to estimate optimal values above the critical average degree c=e/(α-1) where the replica symmetry is broken.

The common mode failures analysis of the redundent system with dependent human error

International Nuclear Information System (INIS)

Kim, M.K.; Chang, S.H.

1983-01-01

Common mode failures (CMFs) have been a serious concern in the nuclear power plant. Thereis a broad category of the failure mechanisms that can cause common mode failures. This paper is a theoretical investigation of the CMFs on the unavailability of the redundent system. It is assumed that the total CMFs consist of the potential CMFs and the dependent human error CMFs. As the human error dependency is higher, the total CMFs are more effected by the dependent human error. If the human error dependence is lower, the system unavailability strongly depends on the potential CMFs, rather than the mechanical failure or the dependent human error. And it is shown that the total CMFs are dominant factor to the unavailability of the redundent system. (Author)

QTL and candidate genes associated with common bacterial blight resistance in the common bean cultivar Longyundou 5 from China

Institute of Scientific and Technical Information of China (English)

Jifeng Zhu; Jing Wu; Lanfen Wang; Matthew W. Blair; Zhendong Zhu; Shumin Wang

2016-01-01

Common bacterial blight (CBB), caused by Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans (Xff), is a worldwide disease of common bean (Phaseolus vulgaris L.). Longyundou 5, a Chinese cultivar in the Mesoamerican gene pool of common bean, displays resistance to the Xff strain XSC3-1. To identify the genetic mechanisms behind this resistance, we crossed Long 5 with a susceptible genotype to develop a mapping population of F2 plants. Plant resistance to CBB was identified at 14 and 21 days after inoculation with Xff strain XSC3-1. A major QTL at 14 and 21 days after inoculation was mapped on chromosome Pv10 with LOD scores of 6.41 and 5.35, respectively. This locus was associated with SAP6, a previously-identified and much-used dominant marker, but in a 4.2 cM interval between new codominant markers BMp10s174 and BMp10s244. Ten candidate genes were found between markers BMp10s174 and BMp10s244 on chromosome Pv10 and could encode defense response proteins responding to CBB pathogens. Four pairs each of epistatic QTL for CBB resistance were detected at 14 and 21 days after inoculation. Phenotypic variation explained by the epistatic QTL ranged from 7.19%to 12.15%and 7.72%to 8.80%at 14 and 21 days after inoculation, respectively. These results confirmed the importance of epistasis in CBB resistance in common bean. The adjacent markers found may be more efficient for marker assisted selection in common bean breeding for CBB resistance owing to their closer linkage to the target QTL.

QTL and candidate genes associated with common bacterial blight resistance in the common bean cultivar Longyundou 5 from China

Institute of Scientific and Technical Information of China (English)

Jifeng; Zhu; Jing; Wu; Lanfen; Wang; Matthew; W.Blair; Zhendong; Zhu; Shumin; Wang

2016-01-01

Common bacterial blight(CBB), caused by Xanthomonas axonopodis pv. phaseoli and Xanthomonas fuscans subsp. fuscans(Xff), is a worldwide disease of common bean(Phaseolus vulgaris L.).Longyundou 5, a Chinese cultivar in the Mesoamerican gene pool of common bean, displays resistance to the Xff strain XSC3-1. To identify the genetic mechanisms behind this resistance,we crossed Long 5 with a susceptible genotype to develop a mapping population of F2 plants.Plant resistance to CBB was identified at 14 and 21 days after inoculation with Xff strain XSC3-1.A major QTL at 14 and 21 days after inoculation was mapped on chromosome Pv10 with LOD scores of 6.41 and 5.35, respectively. This locus was associated with SAP6, a previouslyidentified and much-used dominant marker, but in a 4.2 cM interval between new codominant markers BMp10s174 and BMp10s244. Ten candidate genes were found between markers BMp10s174 and BMp10s244 on chromosome Pv10 and could encode defense response proteins responding to CBB pathogens. Four pairs each of epistatic QTL for CBB resistance were detected at 14 and 21 days after inoculation. Phenotypic variation explained by the epistatic QTL ranged from 7.19% to 12.15% and 7.72% to 8.80% at 14 and 21 days after inoculation, respectively. These results confirmed the importance of epistasis in CBB resistance in common bean. The adjacent markers found may be more efficient for marker assisted selection in common bean breeding for CBB resistance owing to their closer linkage to the target QTL.

Turboprop Propulsion Mechanic.

Science.gov (United States)

Chanute AFB Technical Training Center, IL.

This instructional package consists of a plan of instruction, glossary, and student handouts and exercises for use in training Air Force personnel to become turboprop propulsion mechanics. Addressed in the individual lessons of the course are the following: common hand tools, hardware, measuring devices, and safety wiring; aircraft and engine…

Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

Science.gov (United States)

Sun, Jian; Zhang, Qing; Schlick, Tamar

2005-06-07

Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

Coupling Langevin Dynamics With Continuum Mechanics: Exposing the Role of Sarcomere Stretch Activation Mechanisms to Cardiac Function

Directory of Open Access Journals (Sweden)

Takumi Washio

2018-04-01

Full Text Available High-performance computing approaches that combine molecular-scale and macroscale continuum mechanics have long been anticipated in various fields. Such approaches may enrich our understanding of the links between microscale molecular mechanisms and macroscopic properties in the continuum. However, there have been few successful examples to date owing to various difficulties associated with overcoming the large spatial (from 1 nm to 10 cm and temporal (from 1 ns to 1 ms gaps between the two scales. In this paper, we propose an efficient parallel scheme to couple a microscopic model using Langevin dynamics for a protein motor with a finite element continuum model of a beating heart. The proposed scheme allows us to use a macroscale time step that is an order of magnitude longer than the microscale time step of the Langevin model, without loss of stability or accuracy. This reduces the overhead required by the imbalanced loads of the microscale computations and the communication required when switching between scales. An example of the Langevin dynamics model that demonstrates the usefulness of the coupling approach is the molecular mechanism of the actomyosin system, in which the stretch-activation phenomenon can be successfully reproduced. This microscopic Langevin model is coupled with a macroscopic finite element ventricle model. In the numerical simulations, the Langevin dynamics model reveals that a single sarcomere can undergo spontaneous oscillation (15 Hz accompanied by quick lengthening due to cooperative movements of the myosin molecules pulling on the common Z-line. Also, the coupled simulations using the ventricle model show that the stretch-activation mechanism contributes to the synchronization of the quick lengthening of the sarcomeres at the end of the systolic phase. By comparing the simulation results given by the molecular model with and without the stretch-activation mechanism, we see that this synchronization contributes to

Toward broadband mechanical spectroscopy

DEFF Research Database (Denmark)

Hecksher, Tina; Torchinsky, Darius; Klieber, Christoph

2017-01-01

Diverse material classes exhibit qualitatively similar behavior when made viscous upon cooling toward the glass transition, suggesting a common theoretical basis. We used seven different measurement methods to determine the mechanical relaxation kinetics of a prototype molecular glass former over...

Linking neuroscientific research on decision making to the educational context of novice students assigned to a multiple-choice scientific task involving common misconceptions about electrical circuits

Directory of Open Access Journals (Sweden)

Patrice ePotvin

2014-01-01

Full Text Available Functional magnetic resonance imaging was used to identify the brain-based mechanisms of uncertainty and certainty associated with answers to multiple-choice questions involving common misconceptions about electric circuits. Twenty-two (22 scientifically novice participants (humanities and arts college students were asked, in an fMRI study, whether or not they thought the light bulbs in images presenting electric circuits were lighted up correctly, and if they were certain or uncertain of their answers. When participants reported that they were unsure of their responses, analyses revealed significant activations in brain areas typically involved in uncertainty (anterior cingulate cortex, anterior insula cortex, and superior/dorsomedial frontal cortex and in the left middle/superior temporal lobe. Certainty was associated with large bilateral activations in the occipital and parietal regions usually involved in visuospatial processing. Correct-and-certain answers were associated with activations that suggest a stronger mobilization of visual attention resources when compared to incorrect-and-certain answers. These findings provide insights into brain-based mechanisms of uncertainty that are activated when common misconceptions, identified as such by science education research literature, interfere in decision making in a school-like task. We also discuss the implications of these results from an educational perspective.

Primary non-Hodgkin's lymphoma of the common bile duct: A case report and literature review

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Ali Zakaria

2017-01-01

Full Text Available Hepatobiliary involvement by malignant lymphoma is usually a secondary manifestation of systemic disease, whereas primary non-Hodgkin's lymphoma of the extrahepatic biliary ducts is an extremely rare entity. We describe the case of a 57-year-old man who presented with an acute onset of obstructive jaundice and severe itching. Abdominal ultrasonography and computed tomography revealed intrahepatic and common hepatic ducts dilatation. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed a mid-common bile duct stricture. The patient was presumed to have cholangiocarcinoma of the common bile duct, and an en bloc resection of the tumor with Roux-en-Y hepaticojejunostomy and porta-hepatis lymph nodes dissection was performed. Histopathology and immunohistochemistry revealed a large B cell non-Hodgkin's lymphoma. The patient received six cycles of combination chemotherapy using cyclophosphamide, vincristine, prednisone, and rituximab (CVP-R protocol, and after a 5-year follow-up he is still in complete remission. We also reviewed the cases published from 1982 to 2012, highlighting the challenges in reaching a correct preoperative diagnosis and the treatment modalities used in each case.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity.

Science.gov (United States)

Fiore, Vincenzo G; Dolan, Raymond J; Strausfeld, Nicholas J; Hirth, Frank

2015-12-19

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. © 2015 The Authors.

Morphology and formation mechanism in precipitation of calcite induced by Curvibacter lanceolatus strain HJ-1

Science.gov (United States)

Zhang, Chonghong; Li, Fuchun; Lv, Jiejie

2017-11-01

Precipitation of calcium carbobate induced by microbial activities is common occurrence in controlled solution, but the formation mechanism and morphology in precipitation of calcite in solution systems is unclear, and the role of microbes is disputed. Here, culture experiment was performed for 50 days using the Curvibacter lanceolatus strain HJ-1 in a M2 culture medium, and the phase composition and morphology of the precipitates were characterized by the X-ray diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) techniques. We show that the precipitation processes in our experiment lead to unusual morphologies of crystals corresponding to different growth stages, and the morphologies of the precipitated crystal aggregates ranging from the main rod-, cross-, star-, cauliflower-like morphologies to spherulitic structure. The complex and unusual morphologies of the precipitated calcite by strain HJ-1 may provide a reference point for better understanding the biomineralization mechanism of calcite, moreover, morphological transition of minerals revealed that the multi-ply crystals-aggregation mechanism for calcite growth in crystallisation media.

Computational models reveal a passive mechanism for cell migration in the crypt.

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Sara-Jane Dunn

Full Text Available Cell migration in the intestinal crypt is essential for the regular renewal of the epithelium, and the continued upward movement of cells is a key characteristic of healthy crypt dynamics. However, the driving force behind this migration is unknown. Possibilities include mitotic pressure, active movement driven by motility cues, or negative pressure arising from cell loss at the crypt collar. It is possible that a combination of factors together coordinate migration. Here, three different computational models are used to provide insight into the mechanisms that underpin cell movement in the crypt, by examining the consequence of eliminating cell division on cell movement. Computational simulations agree with existing experimental results, confirming that migration can continue in the absence of mitosis. Importantly, however, simulations allow us to infer mechanisms that are sufficient to generate cell movement, which is not possible through experimental observation alone. The results produced by the three models agree and suggest that cell loss due to apoptosis and extrusion at the crypt collar relieves cell compression below, allowing cells to expand and move upwards. This finding suggests that future experiments should focus on the role of apoptosis and cell extrusion in controlling cell migration in the crypt.

Microstructure and mechanical properties of hypo/hyper-eutectic Al-Si alloys synthesized using a near-net shape forming technique

International Nuclear Information System (INIS)

Gupta, M.; Ling, S.

1999-01-01

In the present study, three aluminum-silicon alloys containing 7, 10 and 19 wt % silicon were synthesized using a novel technique commonly known as disintegrated melt deposition technique. The results following processing revealed that a yield of at least 80% can be achieved after defacing the shrinkage cavity from the as-processed ingots. Microstructural characterization studies conducted on the as-processed samples revealed an increase in the volume fraction of porosity with an increase in silicon content. Porosity levels of 1.07, 1.51 and 2.65% attained in the case of Al-7Si, Al-10Si, and Al-19Si alloys indicates the near-net shape forming capability of the disintegrated melt deposition technique. The results of aging studies conducted on the aluminum-silicon alloys revealed similar aging kinetics irrespective of different silicon content. Results of ambient temperature mechanical tests demonstrate an increase in matrix microhardness and 0.2% yield stress and decrease in ductility with an increase in silicon content in aluminum. Furthermore, the results of an attempt to investigate the effect of extrusion on Al-19Si alloy revealed that the extrusion process significantly assists in reducing porosity and improving microstructural uniformity, 0.2% yield strength, ultimate tensile strength and ductility when compared to the as-processed Al-19Si alloy. The results of microstructural characterization and mechanical properties of aluminum-silicon alloys were finally correlated with the amount of silicon in aluminum and secondary processing technique. (orig.)

Morphodynamic signatures of braiding mechanisms as expressed through change in sediment storage in a gravel-bed river

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Wheaton, Joseph M.; Brasington, James; Darby, Stephen E.; Kasprak, Alan; Sear, David; Vericat, Damiá

2013-06-01

flume-based research on braided channels has revealed four classic mechanisms that produce braiding: central bar development, chute cutoff, lobe dissection, and transverse bar conversion. The importance of these braiding mechanisms relative to other morphodynamic mechanisms in shaping braided rivers has not yet been investigated in the field. Here we exploit repeat topographic surveys of the braided River Feshie (UK) to explore the morphodynamic signatures of different mechanisms of change in sediment storage. Our results indicate that, when combined, the four classic braiding mechanisms do indeed account for the majority of volumetric change in storage in the study reach (61% total). Chute cutoff, traditionally thought of as an erosional braiding mechanism, appears to be the most common braiding mechanism in the study river, but was more the result of deposition during the construction of diagonal bars than it was the erosion of the chute. Three of the four classic mechanisms appeared to be largely net aggradational in nature, whereas secondary mechanisms (including bank erosion, channel incision, and bar sculpting) were primarily net erosional. Although the role of readily erodible banks in facilitating braiding is often conceptualized, we show that bank erosion is as or more important a mechanism in changes in sediment storage than most of the braiding mechanisms, and is the most important "secondary" mechanism (17% of total change). The results of this study provide one of the first field tests of the relative importance of braiding mechanisms observed in flume settings.

Mechanism of porcine liver xanthine oxidoreductase mediated N-oxide reduction of cyadox as revealed by docking and mutagenesis studies.

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Chigang Chen

Full Text Available Xanthine oxidoreductase (XOR is a cytoplasmic molybdenum-containing oxidoreductase, catalyzing both endogenous purines and exogenous compounds. It is suggested that XOR in porcine hepatocytes catalyzes the N-oxide reduction of quinoxaline 1,4-di-N-oxides (QdNOs. To elucidate the molecular mechanism underlying this metabolism, the cDNA of porcine XOR was cloned and heterologously expressed in Spodoptera frugiperda insect cells. The bovine XOR, showing sequence identity of 91% to porcine XOR, was employed as template for homology modeling. By docking cyadox, a representative compound of QdNOs, into porcine XOR model, eight amino acid residues, Gly47, Asn352, Ser360, Arg427, Asp430, Asp431, Ser1227 and Lys1230, were located at distances of less than 4Å to cyadox. Site-directed mutagenesis was performed to analyze their catalytic functions. Compared with wild type porcine XOR, G47A, S360P, D431A, S1227A, and K1230A displayed altered kinetic parameters in cyadox reduction, similarly to that in xanthine oxidation, indicating these mutations influenced electron-donating process of xanthine before subsequent electron transfer to cyadox to fulfill the N-oxide reduction. Differently, R427E and D430H, both located in the 424-434 loop, exhibited a much lower K(m and a decreased V(max respectively in cyadox reduction. Arg427 may be related to the substrate binding of porcine XOR to cyadox, and Asp430 is suggested to be involved in the transfer of electron to cyadox. This study initially reveals the possible catalytic mechanism of porcine XOR in cyadox metabolism, providing with novel insights into the structure-function relationship of XOR in the reduction of exogenous di-N-oxides.

Multi-state nonadiabatic deactivation mechanism of coumarin revealed by ab initio on-the-fly trajectory surface hopping dynamic simulation.

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Gan, Yanzhen; Yue, Ling; Guo, Xugeng; Zhu, Chaoyuan; Cao, Zexing

2017-05-17

An on-the-fly trajectory surface hopping dynamic simulation has been performed for revealing the multi-state nonadiabatic deactivation mechanism of coumarin. The mechanism involves three adiabatic excited states, S 3 (ππ*L b ), S 2 (nπ*, ππ*L a ) and S 1 (ππ*L a , nπ*), and the ground state S 0 at the four state-averaged complete active space self-consistent field, SA4-CASSCF(12,10)/6-31G* level of theory. Upon photoexcitation to the third excited state S 3 (ππ*L b ) in the Franck-Condon region, 80% sampling trajectories decay to the dark S 2 (nπ*) state within an average of 5 fs via the conical intersection S 3 (ππ*L b )/S 2 (nπ*), while 20% decay to the S 2 (ππ*L a ) state within an average of 11 fs via the conical intersection S 3 (ππ*L b )/S 2 (ππ*L a ). Then, sampling trajectories via S 2 (nπ*)/S 1 (ππ*L a ) continue with ultrafast decay processes to give a final distribution of quantum yields as follows: 42% stay on the dark S 1 (nπ*) state, 43.3% go back to the ground S 0 state, 12% undergo a ring-opening reaction to the Z-form S 0 (Z) state, and 2.7% go to the E-form S 0 (E) state. The lifetimes of the excited states are estimated as follows: the S 3 state is about 12 fs on average, the S 2 state is about 80 fs, and the S 1 state has a fast component of about 160 fs and a slow component of 15 ps. The simulated ultrafast radiationless deactivation pathways of photoexcited coumarin immediately interpret the experimentally observed weak fluorescence emission.

Genome Wide Identification, Phylogeny, and Expression of Aquaporin Genes in Common Carp (Cyprinus carpio.

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Chuanju Dong

Full Text Available Aquaporins (Aqps are integral membrane proteins that facilitate the transport of water and small solutes across cell membranes. Among vertebrate species, Aqps are highly conserved in both gene structure and amino acid sequence. These proteins are vital for maintaining water homeostasis in living organisms, especially for aquatic animals such as teleost fish. Studies on teleost Aqps are mainly limited to several model species with diploid genomes. Common carp, which has a tetraploidized genome, is one of the most common aquaculture species being adapted to a wide range of aquatic environments. The complete common carp genome has recently been released, providing us the possibility for gene evolution of aqp gene family after whole genome duplication.In this study, we identified a total of 37 aqp genes from common carp genome. Phylogenetic analysis revealed that most of aqps are highly conserved. Comparative analysis was performed across five typical vertebrate genomes. We found that almost all of the aqp genes in common carp were duplicated in the evolution of the gene family. We postulated that the expansion of the aqp gene family in common carp was the result of an additional whole genome duplication event and that the aqp gene family in other teleosts has been lost in their evolution history with the reason that the functions of genes are redundant and conservation. Expression patterns were assessed in various tissues, including brain, heart, spleen, liver, intestine, gill, muscle, and skin, which demonstrated the comprehensive expression profiles of aqp genes in the tetraploidized genome. Significant gene expression divergences have been observed, revealing substantial expression divergences or functional divergences in those duplicated aqp genes post the latest WGD event.To some extent, the gene families are also considered as a unique source for evolutionary studies. Moreover, the whole set of common carp aqp gene family provides an

Characterisation of the transcriptomes of genetically diverse Listeria monocytogenes exposed to hyperosmotic and low temperature conditions reveal global stress-adaptation mechanisms.

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Juliana Durack

Full Text Available The ability of Listeria monocytogenes to adapt to various food and food- processing environments has been attributed to its robustness, persistence and prevalence in the food supply chain. To improve the present understanding of molecular mechanisms involved in hyperosmotic and low-temperature stress adaptation of L. monocytogenes, we undertook transcriptomics analysis on three strains adapted to sub-lethal levels of these stress stimuli and assessed functional gene response. Adaptation to hyperosmotic and cold-temperature stress has revealed many parallels in terms of gene expression profiles in strains possessing different levels of stress tolerance. Gene sets associated with ribosomes and translation, transcription, cell division as well as fatty acid biosynthesis and peptide transport showed activation in cells adapted to either cold or hyperosmotic stress. Repression of genes associated with carbohydrate metabolism and transport as well as flagella was evident in stressed cells, likely linked to activation of CodY regulon and consequential cellular energy conservation.

Mediastinal Mature Teratoma Revealed by Empyema

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Mohammed Raoufi

2016-01-01

Full Text Available Teratomas are germ cell tumors, manifested with a great variety of clinical features; the most common extragonadal site is the anterior mediastinum. In this case, we report the patient with a large mature mediastinal teratoma with several components of ectodermal and endothermal epithelium. A 24-year-old female patient presented with history of persistent chest pain and progressively aggravating dyspnea for the previous 3 months. A chest X-ray showed a large opacity of the entire left hemithorax. Transcutaneous needle aspiration revealed a purulent fluid. The tube thoracostomy was introduced and the effusion was evacuated. Some weeks later, patient was seen in emergency for persistent cough and lateral chest pain. CT scan revealed a mass of the left hemithorax. The mass showed heterogeneous density, without compressing mediastinum great vessels and left hilar structures. Lipase value was elevated in needle aspiration. The patient underwent a total resection of the mediastinum mass via a left posterolateral thoracotomy. Microscopy revealed a mature teratoma with cystic structures. The patient subsequently made a full recovery. This case provide benign mediastinal teratoma with total atelectasis of left lung and elevated lipase value in needle transcutaneous aspiration; this event is explained by pancreatic component in the cystic tumor. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.

Fossil fuel support mechanisms in Finland

Energy Technology Data Exchange (ETDEWEB)

Lampinen, Ari

2013-10-15

Fossil fuel subsidies and other state support for fossil fuels are forbidden by the Kyoto Protocol and other international treaties. However, they are still commonly used. This publication presents and analyses diverse state support mechanisms for fossil fuels in Finland in 2003-2010. Total of 38 support mechanisms are covered in quantitative analysis and some other mechanisms are mentioned qualitatively only. For some mechanisms the study includes a longer historical perspective. This is the case for tax subsidies for crude oil based traffic fuels that have been maintained in Finland since 1965.

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

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Hongwei Chu

Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

Governance and the Commons in a Multi-Level World

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Derek Armitage

2007-11-01

Full Text Available Multi-level governance may facilitate learning and adaptation in complex social-ecological circumstances. Such arrangements should connect community-based management with regional/national government-level management, link scientific management and traditional management systems, encourage the sharing of knowledge and information, and promote collaboration and dialogue around goals and outcomes. Governance innovations of this type can thus build capacity to adapt to change and manage for resilience. However, critical reflection on the emergence of adaptive, multi-level governance for the commons is warranted. Drawing on examples from the North and South, the purpose of this review is to connect three complementary bodies of scholarship with insights for commons governance in a multi-level world: common property theory, resilience thinking and political ecology. From the commons and resilience literature, normative principles of adaptive, multi-level governance are synthesized (e.g., participation, accountability, leadership, knowledge pluralism, learning and trust. Political ecological interpretations, however, help to reveal the challenge of actualizing these principles and the contextual forces that make entrenched, top-down management systems resilient to change. These forces include the role of power, scale and levels of organization, knowledge valuation, the positioning of social actors and social constructions of nature. Also addressed are the policy narratives that shape governance, and the dialectic relationship among ecological systems and social change. tekst

Genome Sequencing and Mapping Reveal Loss of Heterozygosity as a Mechanism for Rapid Adaptation in the Vegetable Pathogen Phytophthora capsici

Energy Technology Data Exchange (ETDEWEB)

Lamour, Kurt H.; Mudge, Joann; Gobena, Daniel; Hurtado-Gonzales, Oscar P.; Schmutz, Jeremy; Kuo, Alan; Miller, Neil A.; Rice, Brandon J.; Raffaele, Sylvain; Cano, Liliana M.; Bharti, Arvind K.; Donahoo, Ryan S.; Finely, Sabra; Huitema, Edgar; Hulvey, Jon; Platt, Darren; Salamov, Asaf; Savidor, Alon; Sharma, Rahul; Stam, Remco; Sotrey, Dylan; Thines, Marco; Win, Joe; Haas, Brian J.; Dinwiddie, Darrell L.; Jenkins, Jerry; Knight, James R.; Affourtit, Jason P.; Han, Cliff S.; Chertkov, Olga; Lindquist, Erika A.; Detter, Chris; Grigoriev, Igor V.; Kamoun, Sophien; Kingsmore, Stephen F.

2012-02-07

The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diverse isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30percent of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici.

Nutrition, immunological mechanisms and dietary immunomodulation in ADHD

NARCIS (Netherlands)

Verlaet, A.; Briceno Noriega, D.; Hermans, N.; Savelkoul, H.F.J.

2014-01-01

Attention-deficit hyperactivity disorder (ADHD) etiology is not completely understood, but common comorbid dysfunction of the gastrointestinal and immune system suggests that these systems may be affected by a common genetic background and molecular mechanisms. For example, increased levels of

Enhancing Microstructure and Mechanical Properties of AZ31-MWCNT Nanocomposites through Mechanical Alloying

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J. Jayakumar

2013-01-01

Full Text Available Multiwall carbon nanotubes (MWCNTs reinforced Mg alloy AZ31 nanocomposites were fabricated by mechanical alloying and powder metallurgy technique. The reinforcement material MWCNTs were blended in three weight fractions (0.33%, 0.66%, and 1% with the matrix material AZ31 (Al-3%, zinc-1% rest Mg and blended through mechanical alloying using a high energy planetary ball mill. Specimens of monolithic AZ31 and AZ31-MWCNT composites were fabricated through powder metallurgy technique. The microstructure, density, hardness, porosity, ductility, and tensile properties of monolithic AZ31 and AZ31-MWCNT nano composites were characterized and compared. The characterization reveals significant reduction in CNT (carbon nanoTube agglomeration and enhancement in microstructure and mechanical properties due to mechanical alloying through ball milling.

Single-molecule mechanics of protein-labelled DNA handles

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Vivek S. Jadhav

2016-01-01

Full Text Available DNA handles are often used as spacers and linkers in single-molecule experiments to isolate and tether RNAs, proteins, enzymes and ribozymes, amongst other biomolecules, between surface-modified beads for nanomechanical investigations. Custom DNA handles with varying lengths and chemical end-modifications are readily and reliably synthesized en masse, enabling force spectroscopic measurements with well-defined and long-lasting mechanical characteristics under physiological conditions over a large range of applied forces. Although these chemically tagged DNA handles are widely used, their further individual modification with protein receptors is less common and would allow for additional flexibility in grabbing biomolecules for mechanical measurements. In-depth information on reliable protocols for the synthesis of these DNA–protein hybrids and on their mechanical characteristics under varying physiological conditions are lacking in literature. Here, optical tweezers are used to investigate different protein-labelled DNA handles in a microfluidic environment under different physiological conditions. Digoxigenin (DIG-dsDNA-biotin handles of varying sizes (1000, 3034 and 4056 bp were conjugated with streptavidin or neutravidin proteins. The DIG-modified ends of these hybrids were bound to surface-modified polystyrene (anti-DIG beads. Using different physiological buffers, optical force measurements showed consistent mechanical characteristics with long dissociation times. These protein-modified DNA hybrids were also interconnected in situ with other tethered biotinylated DNA molecules. Electron-multiplying CCD (EMCCD imaging control experiments revealed that quantum dot–streptavidin conjugates at the end of DNA handles remain freely accessible. The experiments presented here demonstrate that handles produced with our protein–DNA labelling procedure are excellent candidates for grasping single molecules exposing tags suitable for molecular

What’s In Your Name? Associated Meanings of the Common Filipino Names Among Young Filipinos

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Shaira G. Castillo

2016-11-01

Full Text Available Name is important in knowing someone’s identity. By a person’s name someone can know his or her character. It is also possible that they bear a particular name because of their background and other factors that can lead to something important. This study aimed to find out the associative meanings of the most common Filipino male and female names among the Polytechnic University of the Philippines-Sta. Mesa students. Different factors such as character traits, physical appearance, and skills/talents were considered in determining meanings of the names. The study used quantitative and qualitative research approach, specifically the descriptive method, to analyze the gathered data. A selfadministered survey was distributed to 400 randomly selected respondents. General findings revealed that the respondents associated the most common Filipino male names in the same way regarding character traits and skills/talents. However, they have different associations to the male names in terms of physical appearance. On the other hand, the respondents associated the most common Filipino female names into similar character traits and physical appearance but associated them with different skills/talents. Results also revealed that the most common factors that influence the respondents’ associated meanings were relationships, experiences, popularity, and perception. The results imply that while young Filipinos associate similar character traits, physical appearances and skills to common Filipino names, they have different reasons in giving meanings to them.

Gene expression profiles of Arabidopsis Cvi seeds during dormancy cycling indicate a common underlying dormancy control mechanism.

Science.gov (United States)

Cadman, Cassandra S C; Toorop, Peter E; Hilhorst, Henk W M; Finch-Savage, William E

2006-06-01

Physiologically dormant seeds, like those of Arabidopsis, will cycle through dormant states as seasons change until the environment is favourable for seedling establishment. This phenomenon is widespread in the plant kingdom, but has not been studied at the molecular level. Full-genome microarrays were used for a global transcript analysis of Arabidopsis thaliana (accession Cvi) seeds in a range of dormant and dry after-ripened states during cycling. Principal component analysis of the expression patterns observed showed that they differed in newly imbibed primary dormant seeds, as commonly used in experimental studies, compared with those in the maintained primary and secondary dormant states that exist during cycling. Dormant and after-ripened seeds appear to have equally active although distinct gene expression programmes, dormant seeds having greatly reduced gene expression associated with protein synthesis, potentially controlling the completion of germination. A core set of 442 genes were identified that had higher expression in all dormant states compared with after-ripened states. Abscisic acid (ABA) responsive elements were significantly over-represented in this set of genes the expression of which was enhanced when multiple copies of the elements were present. ABA regulation of dormancy was further supported by expression patterns of key genes in ABA synthesis/catabolism, and dormancy loss in the presence of fluridone. The data support an ABA-gibberelic acid hormone balance mechanism controlling cycling through dormant states that depends on synthetic and catabolic pathways of both hormones. Many of the most highly expressed genes in dormant states were stress-related even in the absence of abiotic stress, indicating that ABA, stress and dormancy responses overlap significantly at the transcriptome level.

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

Energy Technology Data Exchange (ETDEWEB)

Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty; Lin, Yu-Hui; Amani, Mehrnaz; Allali-Hassani, Abdellah; Senisterra, Guillermo; Vedadi, Masoud; Tempel, Wolfram; Mackenzie, Farrell; Chau, Irene; Lourido, Sebastian; Sibley, L. David; Hui, Raymond (Toronto); (WU-MED)

2010-09-21

Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium binding triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.

Parascapular mass revealing primary tuberculosis of the posterior arch

Science.gov (United States)

Arbault, Anais; Ornetti, Paul; Chevallier, Olivier; Avril, Julien; Pottecher, Pierre

2016-01-01

We report the case of a parascapular abscess revealing primary tuberculosis of the posterior arch in a 31-year-old man. Sectional imaging is essential in order to detect the different lesions of this atypical spinal tuberculosis as osteolysis of the posterior arch extendible to vertebral body, osteocondensation, epidural extension which is common in this location, and high specificity of a zygapophysial, costo-vertebral or transverse arthritis. PMID:27709081

Poverty and common mental disorders in developing countries.

Science.gov (United States)

Patel, Vikram; Kleinman, Arthur

2003-01-01

A review of English-language journals published since 1990 and three global mental health reports identified 11 community studies on the association between poverty and common mental disorders in six low- and middle-income countries. Most studies showed an association between indicators of poverty and the risk of mental disorders, the most consistent association being with low levels of education. A review of articles exploring the mechanism of the relationship suggested weak evidence to support a specific association with income levels. Factors such as the experience of insecurity and hopelessness, rapid social change and the risks of violence and physical ill-health may explain the greater vulnerability of the poor to common mental disorders. The direct and indirect costs of mental ill-health worsen the economic condition, setting up a vicious cycle of poverty and mental disorder. Common mental disorders need to be placed alongside other diseases associated with poverty by policy-makers and donors. Programmes such as investment in education and provision of microcredit may have unanticipated benefits in reducing the risk of mental disorders. Secondary prevention must focus on strengthening the ability of primary care services to provide effective treatment.

A Comparison of Over-the-Counter Mechanical Nasal Dilators: A Systematic Review.

Science.gov (United States)

Kiyohara, Nicole; Badger, Christopher; Tjoa, Tjoson; Wong, Brian

2016-09-01

The internal nasal valve is the narrowest part of the nasal airway and a common site of inspiratory collapse and obstruction of nasal airflow. Over-the-counter mechanical nasal dilators are an alternative to surgical intervention that attempts to improve airflow through the internal nasal valve. To determine the efficacy of over-the-counter mechanical nasal dilators and classify these products by mechanism. A database of 33 available over-the-counter mechanical nasal dilators was generated via a PubMed search as well as an internet search via Amazon.com and Google, conducted from April 1, 2013, through December 31, 2015. Products determined to be unavailable or discontinued were excluded from the database. Of the devices examined in published literature, efficacy was based on objective measures, such as measured airflow, the cross-sectional area of the nasal valve, and changes in resistance. Measures of reported sleep quality or patient perception were excluded. An analysis of each product's mechanism revealed 4 broad classes: external nasal dilator strips, nasal stents, nasal clips, and septal stimulators. A review demonstrated 5 studies supporting the use of external nasal dilator strips, 4 studies supporting the use of nasal clips, 1 study supporting the use of nasal stents, and no studies supporting the use of septal stimulators. Our findings suggest that external nasal dilator strips and nasal clips effectively relieve obstruction of the internal nasal valve and may be an alternative to surgical intervention in some patients.

A comparison of maximal bioenergetic enzyme activities obtained with commonly used homogenization techniques.

Science.gov (United States)

Grace, M; Fletcher, L; Powers, S K; Hughes, M; Coombes, J

1996-12-01

Homogenization of tissue for analysis of bioenergetic enzyme activities is a common practice in studies examining metabolic properties of skeletal muscle adaptation to disease, aging, inactivity or exercise. While numerous homogenization techniques are in use today, limited information exists concerning the efficacy of specific homogenization protocols. Therefore, the purpose of this study was to compare the efficacy of four commonly used approaches to homogenizing skeletal muscle for analysis of bioenergetic enzyme activity. The maximal enzyme activity (Vmax) of citrate synthase (CS) and lactate dehydrogenase (LDH) were measured from homogenous muscle samples (N = 48 per homogenization technique) and used as indicators to determine which protocol had the highest efficacy. The homogenization techniques were: (1) glass-on-glass pestle; (2) a combination of a mechanical blender and a teflon pestle (Potter-Elvehjem); (3) a combination of the mechanical blender and a biological detergent; and (4) the combined use of a mechanical blender and a sonicator. The glass-on-glass pestle homogenization protocol produced significantly higher (P pestle homogenization protocol is the technique of choice for studying bioenergetic enzyme activity in skeletal muscle.

Lithium Ion Battery Anode Aging Mechanisms

Science.gov (United States)

Agubra, Victor; Fergus, Jeffrey

2013-01-01

Degradation mechanisms such as lithium plating, growth of the passivated surface film layer on the electrodes and loss of both recyclable lithium ions and electrode material adversely affect the longevity of the lithium ion battery. The anode electrode is very vulnerable to these degradation mechanisms. In this paper, the most common aging mechanisms occurring at the anode during the operation of the lithium battery, as well as some approaches for minimizing the degradation are reviewed. PMID:28809211

The emerging quantum the physics behind quantum mechanics

CERN Document Server

Pena, Luis de la; Valdes-Hernandez, Andrea

2014-01-01

This monograph presents the latest findings from a long-term research project intended to identify the physics behind Quantum Mechanics. A fundamental theory for quantum mechanics is constructed from first physical principles, revealing quantization as an emergent phenomenon arising from a deeper stochastic process. As such, it offers the vibrant community working on the foundations of quantum mechanics an alternative contribution open to discussion. The book starts with a critical summary of the main conceptual problems that still beset quantum mechanics.  The basic consideration is then introduced that any material system is an open system in permanent contact with the random zero-point radiation field, with which it may reach a state of equilibrium. Working from this basis, a comprehensive and self-consistent theoretical framework is then developed. The pillars of the quantum-mechanical formalism are derived, as well as the radiative corrections of nonrelativistic QED, while revealing the underlying physi...

Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

Science.gov (United States)

Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min

2016-02-01

Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Engaging Mindfully with the Commons: A Case of Caribbean Teachers' Experience with ESD

Science.gov (United States)

Down, Lorna

2015-01-01

A study of teachers' responses to Education for Sustainable Development (ESD) in a graduate course in Literature and Education for Sustainable Development, at the School of Education, The University of the West Indies, Mona, revealed that ESD can change indifference to the "commons" to one of mindfulness about local and global…

Connecting 24/5 to Millennials: Providing Academic Support Services from a Learning Commons

Science.gov (United States)

Moore, Anne Cooper; Wells, Kimberly A.

2009-01-01

This study investigates user preferences for reference and technical support, services, and facilities featured in an academic library and Learning Commons through a 23-item questionnaire distributed to building entrants during one 24-hour period on March 14, 2006. Results revealed a strong preference for face-to-face assistance (including…

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

Science.gov (United States)

Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Cell metabolomics reveals the neurotoxicity mechanism of cadmium in PC12 cells.

Science.gov (United States)

Zong, Li; Xing, Junpeng; Liu, Shu; Liu, Zhiqiang; Song, Fengrui

2018-01-01

The heavy metals such as cadmium (Cd) can induce neurotoxicity. Extensive studies about the effects of Cd on human health have been reported, however, a systematic investigation on the molecular mechanisms of the effects of Cd on central nervous system is still needed. In this paper, the neuronal PC-12 cells were treated with a series of concentrations of CdCl 2 for 48h. Then the cytotoxicity was evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. The IC 15 value (15% inhibiting concentration) was selected for further mechanism studies. After PC-12 cells incubated with CdCl 2 at a dose of IC 15 for 48h, the intracellular and extracellular metabolites were profiled using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based cell metabolomics approach. As found, the effects of the heavy metal Cd produced on the PC-12 cell viability were dose-dependent. The metabolic changes were involved in the glycolysis and gluconeogenesis, biopterin metabolism, tryptophan metabolism, tyrosine metabolism, glycerophospholipid metabolism, and fatty acids beta-oxidation. These could cause the perturbation of cell membrane, redox balance, energy supply, cellular detoxification, further affecting the cellular proliferation and apoptosis and other cellular activities. Copyright © 2017 Elsevier Inc. All rights reserved.

Resilience in LGB Youths: A Systematic Review of Protection Mechanisms

Directory of Open Access Journals (Sweden)

Daniela Fonseca Freitas

Full Text Available Abstract: Given the mental health disparities among LGB and heterosexual youth, literature has increasingly emphasized the need to identify the mechanisms that promote resilience among sexual minorities. This systematic review sought to answer the question: what are the protection mechanisms against homophobia among LGB youth? Of the 147 references located in the search, 13 studies were analyzed. The identified protection mechanisms were organized by two criteria: specific to sexual orientation or general, and considered to be at the personal, relational and contextual level. Most of the mechanisms revealed to solely promote the positive adjustment in the presence of risk. General protective mechanisms frequently revealed to be more compensatory of the risks than those specific to sexual orientation.

Mechanical and electro-mechanical properties of three-dimensional nanoporous graphene-poly(vinylidene fluoride composites

Directory of Open Access Journals (Sweden)

G. P. Zheng

2016-09-01

Full Text Available Three-dimensional nanoporous graphene monoliths are utilized to prepare graphene-poly(vinylidene fluoride nanocomposites with enhanced mechanical and electro-mechanical properties. Pre-treatment of the polymer (poly(vinylidene fluoride, PVDF with graphene oxides (GOs facilitates the formation of uniform and thin PVDF films with a typical thickness below 100 nm well coated at the graphene nano-sheets. Besides their excellent compressibility, ductility and mechanical strength, the nanoporous graphene-PVDF nanocomposites are found to possess high sensitivity in strain-dependent electrical conductivity. The improved mechanical and electro-mechanical properties are ascribed to the enhanced crystalline β phase in PVDF which possesses piezoelectricity. The mechanical relaxation analyses on the interfaces between graphene and PVDF reveal that the improved mechanical and electro-mechanical properties could result from the interaction between the –C=O groups in the nanoporous graphene and the –CF2 groups in PVDF, which also explains the important role of GOs in the preparation of the graphene-polymer nanocomposites with superior combined mechanical and electro-mechanical properties.

Competing indentation deformation mechanisms in glass using different strengthening methods

Directory of Open Access Journals (Sweden)

Jian Luo

2016-11-01

Full Text Available Chemical strengthening via ion exchange, thermal tempering, and lamination are proven techniques for strengthening of oxide glasses. For each of these techniques, the strengthening mechanism is conventionally ascribed to the linear superposition of the compressive stress profile on the glass surface. However, in this work we use molecular dynamics simulations to reveal the underlying indentation deformation mechanism beyond the simple linear superposition of compressive and indentation stresses. In particular, the plastic zone can be dramatically different from the commonly assumed hemispherical shape, which leads to a completely different stress field and resulting crack system. We show that the indentation-induced fracture is controlled by two competing mechanisms: the compressive stress itself and a potential reduction in free volume that can increase the driving force for crack formation. Chemical strengthening via ion exchange tends to escalate the competition between these two effects, while thermal tempering tends to reduce it. Lamination of glasses with differential thermal expansion falls in between. The crack system also depends on the indenter geometry and the loading stage, i.e., loading vs. after unloading. It is observed that combining thermal tempering or high free volume content with ion exchange or lamination can impart a relatively high compressive stress and reduce the driving force for crack formation. Therefore, such a combined approach might offer the best overall crack resistance for oxide glasses.

Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms.

Science.gov (United States)

DePina, Ana S; Iser, Wendy B; Park, Sung-Soo; Maudsley, Stuart; Wilson, Mark A; Wolkow, Catherine A

2011-07-12

Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms

Directory of Open Access Journals (Sweden)

Wilson Mark A

2011-07-01

Full Text Available Abstract Background Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. Results In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS. We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+ sperm. However, yolk protein (YP levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. Conclusions C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

Variable-Length Coding with Stop-Feedback for the Common-Message Broadcast Channel

DEFF Research Database (Denmark)

Trillingsgaard, Kasper Fløe; Yang, Wei; Durisi, Giuseppe

2016-01-01

This paper investigates the maximum coding rate over a K-user discrete memoryless broadcast channel for the scenario where a common message is transmitted using variable-length stop-feedback codes. Specifically, upon decoding the common message, each decoder sends a stop signal to the encoder...... of these bounds reveal that---contrary to the point-to-point case---the second-order term in the asymptotic expansion of the maximum coding rate decays inversely proportional to the square root of the average blocklength. This holds for certain nontrivial common-message broadcast channels, such as the binary......, which transmits continuously until it receives all K stop signals. We present nonasymptotic achievability and converse bounds for the maximum coding rate, which strengthen and generalize the bounds previously reported in Trillingsgaard et al. (2015) for the two-user case. An asymptotic analysis...

Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

Science.gov (United States)

Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

2017-02-01

Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

Partial Avulsion of Common Bile Duct and Duodenal Perforation in a Blunt Abdominal Trauma

OpenAIRE

Mirza, Bilal; Ijaz, Lubna; Iqbal, Shahid; Sheikh, Afzal

2010-01-01

Complete or partial avulsion of common bile duct is a very rare injury following blunt abdominal trauma in children. A 7-year old boy presented to ER following blunt abdominal trauma by a moving motorcycle. X ray abdomen revealed free air under diaphragm and CT scan showed pancreatic contusion injury. At operation anterior wall of common bile duct (CBD) along with a 2mm rim of duodenal tissue on either side of anterior wall of CBD were found avulsed from the duodenum. The avulsed portion of C...

Is There a Common Summary Statistical Process for Representing the Mean and Variance? A Study Using Illustrations of Familiar Items.

Science.gov (United States)

Yang, Yi; Tokita, Midori; Ishiguchi, Akira

2018-01-01

A number of studies revealed that our visual system can extract different types of summary statistics, such as the mean and variance, from sets of items. Although the extraction of such summary statistics has been studied well in isolation, the relationship between these statistics remains unclear. In this study, we explored this issue using an individual differences approach. Observers viewed illustrations of strawberries and lollypops varying in size or orientation and performed four tasks in a within-subject design, namely mean and variance discrimination tasks with size and orientation domains. We found that the performances in the mean and variance discrimination tasks were not correlated with each other and demonstrated that extractions of the mean and variance are mediated by different representation mechanisms. In addition, we tested the relationship between performances in size and orientation domains for each summary statistic (i.e. mean and variance) and examined whether each summary statistic has distinct processes across perceptual domains. The results illustrated that statistical summary representations of size and orientation may share a common mechanism for representing the mean and possibly for representing variance. Introspections for each observer performing the tasks were also examined and discussed.

Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries

Energy Technology Data Exchange (ETDEWEB)

Berger, Nicole [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Andreisek, Gustav; Karer, Anissja T.; Manoliu, Andrei; Ulbrich, Erika J. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Bouaicha, Samy [University Hospital Zurich, Department of Trauma Surgery, Zurich (Switzerland); Naraghi, Ali [University of Toronto, Department of Medical Imaging, Mount Sinai Hospital and the University Health Network, Toronto, ON (Canada); Seifert, Burkhardt [University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Department of Biostatistics, Zurich (Switzerland)

2017-01-15

To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. (orig.)

Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries

International Nuclear Information System (INIS)

Berger, Nicole; Andreisek, Gustav; Karer, Anissja T.; Manoliu, Andrei; Ulbrich, Erika J.; Bouaicha, Samy; Naraghi, Ali; Seifert, Burkhardt

2017-01-01

To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. (orig.)

Influence of septic system wastewater treatment on titanium dioxide nanoparticle subsurface transport mechanisms.

Science.gov (United States)

Waller, Travis; Marcus, Ian M; Walker, Sharon L

2018-06-04

Engineered nanomaterials (ENMs) are commonly incorporated into food and consumer applications to enhance a specific product aspect (i.e., optical properties). Life cycle analyses revealed ENMs can be released from products during usage and reach wastewater treatment plants (WWTPs), with titanium dioxide (TiO 2 ) accounting for a large fraction. As such, food grade (FG) TiO 2 , a more common form of TiO 2 in wastewater, was used in this study. Nanomaterials in WWTPs have been well characterized, although the problematic septic system has been neglected. Elution and bioaccumulation of TiO 2 ENMs from WTTPs in downriver sediments and microorganisms has been observed; however, little is known about mechanisms governing the elution of FG TiO 2 from the septic drainage system. This study characterized the transport behavior and mechanisms of FG TiO 2 particles in porous media conditions after septic waste treatment. FG and industrial grade (IG) TiO 2 (more commonly studied) were introduced to septic tank effluent and low-ionic strength electrolyte solutions prior to column transport experiments. Results indicate that FG TiO 2 aggregate size (200-400 nm) remained consistent across solutions. Additionally, elution of FG and IG TiO 2 was greatest in septic effluent at the higher nanoparticle concentration (100 ppm). FG TiO 2 was well retained at the low (2 ppm) concentration in septic effluent, suggesting that particles that escape the septic system may still be retained in drainage field before reaching the groundwater system, although eluted particles are highly stabilized. Findings provide valuable insight into the significance of the solution environment at mediating differences observed between uniquely engineered nanomaterials. Graphical abstract.

Comparative genomics reveals conservative evolution of the xylem transcriptome in vascular plants.

Science.gov (United States)

Li, Xinguo; Wu, Harry X; Southerton, Simon G

2010-06-21

Wood is a valuable natural resource and a major carbon sink. Wood formation is an important developmental process in vascular plants which played a crucial role in plant evolution. Although genes involved in xylem formation have been investigated, the molecular mechanisms of xylem evolution are not well understood. We use comparative genomics to examine evolution of the xylem transcriptome to gain insights into xylem evolution. The xylem transcriptome is highly conserved in conifers, but considerably divergent in angiosperms. The functional domains of genes in the xylem transcriptome are moderately to highly conserved in vascular plants, suggesting the existence of a common ancestral xylem transcriptome. Compared to the total transcriptome derived from a range of tissues, the xylem transcriptome is relatively conserved in vascular plants. Of the xylem transcriptome, cell wall genes, ancestral xylem genes, known proteins and transcription factors are relatively more conserved in vascular plants. A total of 527 putative xylem orthologs were identified, which are unevenly distributed across the Arabidopsis chromosomes with eight hot spots observed. Phylogenetic analysis revealed that evolution of the xylem transcriptome has paralleled plant evolution. We also identified 274 conifer-specific xylem unigenes, all of which are of unknown function. These xylem orthologs and conifer-specific unigenes are likely to have played a crucial role in xylem evolution. Conifers have highly conserved xylem transcriptomes, while angiosperm xylem transcriptomes are relatively diversified. Vascular plants share a common ancestral xylem transcriptome. The xylem transcriptomes of vascular plants are more conserved than the total transcriptomes. Evolution of the xylem transcriptome has largely followed the trend of plant evolution.

The mechanical role of the cervix in pregnancy

Science.gov (United States)

Myers, Kristin M.; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J.; Hall, Timothy J.; House, Michael

2015-01-01

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineation of normal and abnormal cervical function in pregnancy. PMID:25841293

Mechanism study of pulsus paradoxus using mechanical models.

Directory of Open Access Journals (Sweden)

Chang-yang Xing

Full Text Available Pulsus paradoxus is an exaggeration of the normal inspiratory decrease in systolic blood pressure. Despite a century of attempts to explain this sign consensus is still lacking. To solve the controversy and reveal the exact mechanism, we reexamined the characteristic anatomic arrangement of the circulation system in the chest and designed these mechanical models based on related hydromechanic principles. Model 1 was designed to observe the primary influence of respiratory intrathoracic pressure change (RIPC on systemic and pulmonary venous return systems (SVR and PVR respectively. Model 2, as an equivalent mechanical model of septal swing, was to study the secondary influence of RIPC on the motion of the interventriclar septum (IVS, which might be the direct cause for pulsus paradoxus. Model 1 demonstrated that the simulated RIPC had different influence on the simulated SVR and PVR. It increased the volume of the simulated right ventricle (SRV when the internal pressure was kept constant (8.16 cmH2O, while it had the opposite effect on PVR. Model 2 revealed the three major factors determining the respiratory displacement of IVS in normal and different pathophysiological conditions: the magnitude of RIPC, the pressure difference between the two ventricles and the intrapericardial pressure. Our models demonstrate that the different anatomical arrangement of the two venous return systems leads to a different effect of RIPC on right and left ventricles, and thus a pressure gradient across IVS that tends to shift IVS left- and rightwards. When the leftward displacement of IVS reaches a considerable amplitude in some pathologic condition such as cardiac tamponade, the pulsus paradoxus occurs.

Role of failure-mechanism identification in accelerated testing

Science.gov (United States)

Hu, J. M.; Barker, D.; Dasgupta, A.; Arora, A.

1993-01-01

Accelerated life testing techniques provide a short-cut method to investigate the reliability of electronic devices with respect to certain dominant failure mechanisms that occur under normal operating conditions. However, accelerated tests have often been conducted without knowledge of the failure mechanisms and without ensuring that the test accelerated the same mechanism as that observed under normal operating conditions. This paper summarizes common failure mechanisms in electronic devices and packages and investigates possible failure mechanism shifting during accelerated testing.

Common Input to Motor Units of Intrinsic and Extrinsic Hand Muscles During Two-Digit Object Hold

OpenAIRE

Winges, Sara A.; Kornatz, Kurt W.; Santello, Marco

2008-01-01

Anatomical and physiological evidence suggests that common input to motor neurons of hand muscles is an important neural mechanism for hand control. To gain insight into the synaptic input underlying the coordination of hand muscles, significant effort has been devoted to describing the distribution of common input across motor units of extrinsic muscles. Much less is known, however, about the distribution of common input to motor units belonging to different intrinsic muscles and to intrinsi...

Beta-Glucan induced immune modulation of wound healing in common carp (Cyprinus carpio)

OpenAIRE

Jiménez, Natalia Ivonne Vera; Nielsen, Michael Engelbrecht; Lindenstrøm, Thomas

2012-01-01

Immune modulators are compounds capable to interact with the immune system and to modify the host response. This interaction enhances non-specific defense mechanisms, improving health and promoting survival. β-glucans are glucose polysaccharides present in sea weed, bacteria, fungi and cereal but not in animals. β-glucans are commonly used as immune modulators, but the mechanisms through which the modulation is achieved remains to be understood. Wound healing and tissue regeneration are essen...

Cytotoxicity of polycations: Relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity.

Science.gov (United States)

Monnery, Bryn D; Wright, Michael; Cavill, Rachel; Hoogenboom, Richard; Shaunak, Sunil; Steinke, Joachim H G; Thanou, Maya

2017-04-15

The mechanism of polycation cytotoxicity and the relationship to polymer molecular weight is poorly understood. To gain an insight into this important phenomenon a range of newly synthesised uniform (near monodisperse) linear polyethylenimines, commercially available poly(l-lysine)s and two commonly used PEI-based transfectants (broad 22kDa linear and 25kDa branched) were tested for their cytotoxicity against the A549 human lung carcinoma cell line. Cell membrane damage assays (LDH release) and cell viability assays (MTT) showed a strong relationship to dose and polymer molecular weight, and increasing incubation times revealed that even supposedly "non-toxic" low molecular weight polymers still damage cell membranes. The newly proposed mechanism of cell membrane damage is acid catalysed hydrolysis of lipidic phosphoester bonds, which was supported by observations of the hydrolysis of DOPC liposomes. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Skin mechanical properties and modeling: A review.

Science.gov (United States)

Joodaki, Hamed; Panzer, Matthew B

2018-04-01

The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.

Common Agency and Coordinated Bids in Sponsored Search Auctions

OpenAIRE

Maris Goldmanis; Antonio Penta; Francesco Decarolis

2012-01-01

As auctions are becoming the main mechanism for selling advertisement space on the web, marketing agencies specialized in bidding in online auctions are proliferating. We analyze theoretically how bidding delegation to a common marketing agency can undermine both revenues and efficiency of the generalized second price auction, the format used by Google and Microsoft-Yahoo!. Our characterization allows us to quantify the revenue losses relative to both the case of full competition and the case...

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones.

Science.gov (United States)

Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Ozbek, Suat; Technau, Ulrich; Gurevitz, Michael

2012-04-07

Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

Discovery of cancer common and specific driver gene sets

Science.gov (United States)

2017-01-01

Abstract Cancer is known as a disease mainly caused by gene alterations. Discovery of mutated driver pathways or gene sets is becoming an important step to understand molecular mechanisms of carcinogenesis. However, systematically investigating commonalities and specificities of driver gene sets among multiple cancer types is still a great challenge, but this investigation will undoubtedly benefit deciphering cancers and will be helpful for personalized therapy and precision medicine in cancer treatment. In this study, we propose two optimization models to de novo discover common driver gene sets among multiple cancer types (ComMDP) and specific driver gene sets of one certain or multiple cancer types to other cancers (SpeMDP), respectively. We first apply ComMDP and SpeMDP to simulated data to validate their efficiency. Then, we further apply these methods to 12 cancer types from The Cancer Genome Atlas (TCGA) and obtain several biologically meaningful driver pathways. As examples, we construct a common cancer pathway model for BRCA and OV, infer a complex driver pathway model for BRCA carcinogenesis based on common driver gene sets of BRCA with eight cancer types, and investigate specific driver pathways of the liquid cancer lymphoblastic acute myeloid leukemia (LAML) versus other solid cancer types. In these processes more candidate cancer genes are also found. PMID:28168295

Reversible Guest Exchange Mechanisms in Supramolecular Host-GuestAssemblies

Energy Technology Data Exchange (ETDEWEB)

Pluth, Michael D.; Raymond, Kenneth N.

2006-09-01

Synthetic chemists have provided a wide array of supramolecular assemblies able to encapsulate guest molecules. The scope of this tutorial review focuses on supramolecular host molecules capable of reversibly encapsulating polyatomic guests. Much work has been done to determine the mechanism of guest encapsulation and guest release. This review covers common methods of monitoring and characterizing guest exchange such as NMR, UV-VIS, mass spectroscopy, electrochemistry, and calorimetry and also presents representative examples of guest exchange mechanisms. The guest exchange mechanisms of hemicarcerands, cucurbiturils, hydrogen-bonded assemblies, and metal-ligand assemblies are discussed. Special attention is given to systems which exhibit constrictive binding, a motif common in supramolecular guest exchange systems.

Constructing Common Information Space across Distributed Emergency Medical Teams

DEFF Research Database (Denmark)

Zhang, Zhan; Sarcevic, Aleksandra; Bossen, Claus

2017-01-01

This paper examines coordination and real-time information sharing across four emergency medical teams in a high-risk and distributed setting as they provide care to critically injured patients within the first hour after injury. Through multiple field studies we explored how common understanding...... of critical patient data is established across these heterogeneous teams and what coordination mechanisms are being used to support information sharing and interpretation. To analyze the data, we drew on the concept of Common Information Spaces (CIS). Our results showed that teams faced many challenges...... in achieving efficient information sharing and coordination, including difficulties in locating and assembling team members, communicating and interpreting information from the field, and accommodating differences in team goals and information needs, all while having minimal technology support. We reflect...

On uncertainty relations in quantum mechanics

International Nuclear Information System (INIS)

Ignatovich, V.K.

2004-01-01

Uncertainty relations (UR) are shown to have nothing specific for quantum mechanics (QM), being the general property valid for the arbitrary function. A wave function of a particle simultaneously having a precisely defined position and momentum in QM is demonstrated. Interference on two slits in a screen is shown to exist in classical mechanics. A nonlinear classical system of equations replacing the QM Schroedinger equation is suggested. This approach is shown to have nothing in common with the Bohm mechanics

Examining the media portrayal of obesity through the lens of the Common Sense Model of Illness Representations.

Science.gov (United States)

De Brún, Aoife; McCarthy, Mary; McKenzie, Kenneth; McGloin, Aileen

2015-01-01

This study examined the Irish media discourse on obesity by employing the Common Sense Model of Illness Representations. A media sample of 368 transcripts was compiled from newspaper articles (n = 346), radio discussions (n = 5), and online news articles (n = 17) on overweight and obesity from the years 2005, 2007, and 2009. Using the Common Sense Model and framing theory to guide the investigation, a thematic analysis was conducted on the media sample. Analysis revealed that the behavioral dimensions of diet and activity levels were the most commonly cited causes of and interventions in obesity. The advertising industry was blamed for obesity, and there were calls for increased government action to tackle the issue. Physical illness and psychological consequences of obesity were prevalent in the sample, and analysis revealed that the economy, regardless of its state, was blamed for obesity. These results are discussed in terms of expectations of audience understandings of the issue and the implications of these dominant portrayals and framings on public support for interventions. The article also outlines the value of a qualitative analytical framework that combines the Common Sense Model and framing theory in the investigation of illness narratives.

Revealing time bunching effect in single-molecule enzyme conformational dynamics.

Science.gov (United States)

Lu, H Peter

2011-04-21

In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a

Revealing Nanoscale Passivation and Corrosion Mechanisms of Reactive Battery Materials in Gas Environments.

Science.gov (United States)

Li, Yuzhang; Li, Yanbin; Sun, Yongming; Butz, Benjamin; Yan, Kai; Koh, Ai Leen; Zhao, Jie; Pei, Allen; Cui, Yi

2017-08-09

Lithium (Li) metal is a high-capacity anode material (3860 mAh g -1 ) that can enable high-energy batteries for electric vehicles and grid-storage applications. However, Li metal is highly reactive and repeatedly consumed when exposed to liquid electrolyte (during battery operation) or the ambient environment (throughout battery manufacturing). Studying these corrosion reactions on the nanoscale is especially difficult due to the high chemical reactivity of both Li metal and its surface corrosion films. Here, we directly generate pure Li metal inside an environmental transmission electron microscope (TEM), revealing the nanoscale passivation and corrosion process of Li metal in oxygen (O 2 ), nitrogen (N 2 ), and water vapor (H 2 O). We find that while dry O 2 and N 2 (99.9999 vol %) form uniform passivation layers on Li, trace water vapor (∼1 mol %) disrupts this passivation and forms a porous film on Li metal that allows gas to penetrate and continuously react with Li. To exploit the self-passivating behavior of Li in dry conditions, we introduce a simple dry-N 2 pretreatment of Li metal to form a protective layer of Li nitride prior to battery assembly. The fast ionic conductivity and stable interface of Li nitride results in improved battery performance with dendrite-free cycling and low voltage hysteresis. Our work reveals the detailed process of Li metal passivation/corrosion and demonstrates how this mechanistic insight can guide engineering solutions for Li metal batteries.

Prostate cancer revealed by skin metastasis: A case report in black ...

African Journals Online (AJOL)

Introduction: Prostate cancer is the most common male malignancy in Togo. Most patients present with advanced and metastatic disease. Skin metastasis from prostate cancer is very rare and it occurs late and often with a poor prognosis. We report a case in a 52-year-old Togolese man where the skin lesions reveal the ...

Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

Science.gov (United States)

Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

2018-01-01

The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Insights into the catalytic mechanism of dehydrogenase BphB: A quantum mechanics/molecular mechanics study.

Science.gov (United States)

Zhang, Ruiming; Shi, Xiangli; Sun, Yanhui; Zhang, Qingzhu; Wang, Wenxing

2018-05-17

The present study delineated the dehydrogenation mechanism of cis-2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DDBPH) and cis-2,3-dihydro-2,3-dihydroxy-4,4'-dichlorobiphenyl (2,3-DD-4,4'-DBPH) by Pandoraea pnomenusa strain B-356 cis-2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase (BphB) in atomistic detail. The enzymatic process was investigated by a combined quantum mechanics/molecular mechanics (QM/MM) approach. Five different snapshots were extracted and calculated, which revealed that the Boltzmann-weighted average barriers of 2,3-DDBPH and 2,3-DD-4,4'-DBPH dehydrogenation processes are 10.7 and 11.5 kcal mol -1 , respectively. The established dehydrogenation mechanism provides new insight into the degradation processes of other chlorinated 2,3-DDBPH. In addition to Asn115, Ser142, and Lys149, the importance of Ile 89, Asn143, Pro184, Met 187, Thr189, and Lue 191 during the dehydrogenation process of 2,3-DDBPH and 2,3-DD-4,4'-DBPH were also highlighted to search for promising mutation targets for improving the catalytic efficiency of BphB. Copyright © 2018. Published by Elsevier Ltd.

Thiamine deficiency impairs common eider (Somateria mollissima) reproduction in the field.

Science.gov (United States)

Mörner, Torsten; Hansson, Tomas; Carlsson, Le; Berg, Anna-Lena; Ruiz Muñoz, Yolanda; Gustavsson, Hanna; Mattsson, Roland; Balk, Lennart

2017-10-31

The Baltic Sea population of the common eider (Somateria mollissima) has declined dramatically during the last two decades. Recently, widespread episodic thiamine (vitamin B 1 ) deficiency has been demonstrated in feral birds and suggested to contribute significantly to declining populations. Here we show that the decline of the common eider population in the Baltic Sea is paralleled by high mortality of the pulli a few days after hatch, owing to thiamine deficiency and probably also thereby associated abnormal behaviour resulting in high gull predation. An experiment with artificially incubated common eider eggs collected in the field revealed that thiamine treatment of pulli had a therapeutic effect on the thiamine status of the brain and prevented death. The mortality was 53% in untreated specimens, whereas it was only 7% in thiamine treated specimens. Inability to dive was also linked to brain damage typical for thiamine deficiency. Our results demonstrate how thiamine deficiency causes a range of symptoms in the common eider pulli, as well as massive die-offs a few days after hatch, which probably are the major explanation of the recent dramatic population declines.

Perivalvular pannus and valve thrombosis: two concurrent mechanisms of mechanical valve prosthesis dysfunction.

Science.gov (United States)

Arnáiz-García, María Elena; González-Santos, Jose María; Bueno-Codoñer, María E; López-Rodríguez, Javier; Dalmau-Sorlí, María José; Arévalo-Abascal, Adolfo; Arribas-Jiménez, Antonio; Diego-Nieto, Alejandro; Rodríguez-Collado, Javier; Rodríguez-López, Jose María

2015-02-01

A 78-year-old woman was admitted to our institution with progressive dyspnea. She had previously been diagnosed with rheumatic heart disease and had undergone cardiac surgery for mechanical mitral valve replacement ten years previously. Transesophageal echocardiography revealed blockage of the mechanical prosthesis and the patient was scheduled for surgery, in which a thrombus was removed from the left atrial appendage. A partial thrombosis of the mechanical prosthesis and circumferential pannus overgrowth were concomitantly detected. Prosthetic heart valve blockage is a rare but life-threatening complication, the main causes of which are thrombosis and pannus formation. The two conditions are different but both are usually misdiagnosed. Two concurrent mechanisms of prosthesis blockage were found in this patient. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Digital gene atlas of neonate common marmoset brain.

Science.gov (United States)

Shimogori, Tomomi; Abe, Ayumi; Go, Yasuhiro; Hashikawa, Tsutomu; Kishi, Noriyuki; Kikuchi, Satomi S; Kita, Yoshiaki; Niimi, Kimie; Nishibe, Hirozumi; Okuno, Misako; Saga, Kanako; Sakurai, Miyano; Sato, Masae; Serizawa, Tsuna; Suzuki, Sachie; Takahashi, Eiki; Tanaka, Mami; Tatsumoto, Shoji; Toki, Mitsuhiro; U, Mami; Wang, Yan; Windak, Karl J; Yamagishi, Haruhiko; Yamashita, Keiko; Yoda, Tomoko; Yoshida, Aya C; Yoshida, Chihiro; Yoshimoto, Takuro; Okano, Hideyuki

2018-03-01

Interest in the common marmoset (Callithrix jacchus) as a primate model animal has grown recently, in part due to the successful demonstration of transgenic marmosets. However, there is some debate as to the suitability of marmosets, compared to more widely used animal models, such as the macaque monkey and mouse. Especially, the usage of marmoset for animal models of human cognition and mental disorders, is still yet to be fully explored. To examine the prospects of the marmoset model for neuroscience research, the Marmoset Gene Atlas (https://gene-atlas.bminds.brain.riken.jp/) provides a whole brain gene expression atlas in the common marmoset. We employ in situ hybridization (ISH) to systematically analyze gene expression in neonate marmoset brains, which allows us to compare expression with other model animals such as mouse. We anticipate that these data will provide sufficient information to develop tools that enable us to reveal marmoset brain structure, function, cellular and molecular organization for primate brain research. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Stress-related phenomena and detoxification mechanisms induced by common pharmaceuticals in alfalfa (Medicago sativa L.) plants

International Nuclear Information System (INIS)

Christou, Anastasis; Antoniou, Chrystalla; Christodoulou, Charalampia; Hapeshi, Evroula; Stavrou, Ioannis; Michael, Costas; Fatta-Kassinos, Despo; Fotopoulos, Vasileios

2016-01-01

Pharmaceutically active compounds (PhACs) have been recently shown to exert phytotoxic effects. The present study explores the uptake, systemic translocation, and abiotic stress responses and detoxification mechanisms induced by the exposure of alfalfa plants grown in sand under greenhouse conditions to four common, individually applied PhACs (10 μg L −1 ) (diclofenac, sulfamethoxazole, trimethoprim, 17a-ethinylestradiol) and their mixture. Stress physiology markers (lipid peroxidation, proline, H 2 O 2 and NO content, antioxidant activity assays) and gene expression levels of key plant detoxification components (including glutathione S-transferases, GST7, GST17; superoxide dismutases, CuZnSOD, FeSOD; proton pump, H + -ATP, and cytochrome c oxidase, CytcOx), were evaluated. PhACs were detected in significantly higher concentrations in roots compared with leaves. Stress related effects, manifested via membrane lipid peroxidation and oxidative burst, were local (roots) rather than systemic (leaves), and exacerbated when the tested PhACs were applied in mixture. Systemic accumulation of H 2 O 2 in leaves suggests its involvement in signal transduction and detoxification responses. Increased antioxidant enzymatic activities, as well as upregulated transcript levels of GST7, GST17, H + -ATPase and CytcOx, propose their role in the detoxification of the selected PhACs in plants. The current findings provide novel biochemical and molecular evidence highlighting the studied PhACs as an emerging abiotic stress factor, and point the need for further research on wastewater flows under natural agricultural environments. - Highlights: • PhACs were detected in higher concentrations in roots compared with leaves. • Stress effects were local and exacerbated when PhACs were applied in mixture. • H 2 O 2 may be involved in signal transduction and detoxification responses. • GSTs, H + -ATPase and CytcOx contribute to the detoxification of PhACs in plants. • Results

Stress-related phenomena and detoxification mechanisms induced by common pharmaceuticals in alfalfa (Medicago sativa L.) plants

Energy Technology Data Exchange (ETDEWEB)

Christou, Anastasis [Agricultural Research Institute, P.O. Box 22016, 1516 Nicosia (Cyprus); Antoniou, Chrystalla; Christodoulou, Charalampia [Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, 3603 Lemesos (Cyprus); Hapeshi, Evroula; Stavrou, Ioannis; Michael, Costas [NIREAS-International Water Research Center, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Fatta-Kassinos, Despo [Department of Civil and Environmental Engineering, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); NIREAS-International Water Research Center, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Fotopoulos, Vasileios, E-mail: vassilis.fotopoulos@cut.ac.cy [Department of Agricultural Sciences, Biotechnology and Food Science, Cyprus University of Technology, 3603 Lemesos (Cyprus)

2016-07-01

Pharmaceutically active compounds (PhACs) have been recently shown to exert phytotoxic effects. The present study explores the uptake, systemic translocation, and abiotic stress responses and detoxification mechanisms induced by the exposure of alfalfa plants grown in sand under greenhouse conditions to four common, individually applied PhACs (10 μg L{sup −1}) (diclofenac, sulfamethoxazole, trimethoprim, 17a-ethinylestradiol) and their mixture. Stress physiology markers (lipid peroxidation, proline, H{sub 2}O{sub 2} and NO content, antioxidant activity assays) and gene expression levels of key plant detoxification components (including glutathione S-transferases, GST7, GST17; superoxide dismutases, CuZnSOD, FeSOD; proton pump, H{sup +}-ATP, and cytochrome c oxidase, CytcOx), were evaluated. PhACs were detected in significantly higher concentrations in roots compared with leaves. Stress related effects, manifested via membrane lipid peroxidation and oxidative burst, were local (roots) rather than systemic (leaves), and exacerbated when the tested PhACs were applied in mixture. Systemic accumulation of H{sub 2}O{sub 2} in leaves suggests its involvement in signal transduction and detoxification responses. Increased antioxidant enzymatic activities, as well as upregulated transcript levels of GST7, GST17, H{sup +}-ATPase and CytcOx, propose their role in the detoxification of the selected PhACs in plants. The current findings provide novel biochemical and molecular evidence highlighting the studied PhACs as an emerging abiotic stress factor, and point the need for further research on wastewater flows under natural agricultural environments. - Highlights: • PhACs were detected in higher concentrations in roots compared with leaves. • Stress effects were local and exacerbated when PhACs were applied in mixture. • H{sub 2}O{sub 2} may be involved in signal transduction and detoxification responses. • GSTs, H{sup +}-ATPase and CytcOx contribute to the

Stochastic modelling in design of mechanical properties of nanometals

International Nuclear Information System (INIS)

Tengen, T.B.; Wejrzanowski, T.; Iwankiewicz, R.; Kurzydlowski, K.J.

2010-01-01

Polycrystalline nanometals are being fabricated through different processing routes and conditions. The consequence is that nanometals having the same mean grain size may have different grain size dispersion and, hence, may have different material properties. This has often led to conflicting reports from both theoretical and experimental findings about the evolutions of the mechanical properties of nanomaterials. The present paper employs stochastic model to study the impact of microstructure evolution during grain growth on the mechanical properties of polycrystalline nanometals. The stochastic model for grain growth and the stochastic model for changes in mechanical properties of nanomaterials are proposed. The model for the mechanical properties developed is tested on aluminium samples.Many salient features of the mechanical properties of the aluminium samples are revealed. The results show that the different mechanisms of grain growth impart different nature of response to the material mechanical properties. The conventional, homologous and anomalous temperature dependences of the yield stress have also been revealed to be due to different nature of interactions of the microstructures during evolution.

Advantages and controversy of common agricultural and cohesion policy in the EU

Directory of Open Access Journals (Sweden)

Kostić Vladimir

2016-01-01

Full Text Available The authors explore deals and payments that have a positive effect on the development of Common agricultural and cohesion policy. They particularly emphasize the ways of protecting the European Union from cheap imported products from non-EU countries. They also deal with the mechanisms that are built into the process, with the structural policy regarding 'Agenda 2000', as well as the reforms of Common agricultural and cohesion policy from its beginnings until now. The paper presents problems of guaranteed prices, ecology, quotas, agricultural levies and customs duties. The authors also investigated the Common Agricultural and Rural Policy of the European Union 2014-2020, the ways to accelerate the transfer of technology and strengthen the cooperation between agriculture and research sectors in the future.

Genome-Wide Identification, Characterization and Phylogenetic Analysis of ATP-Binding Cassette (ABC) Transporter Genes in Common Carp (Cyprinus carpio).

Science.gov (United States)

Liu, Xiang; Li, Shangqi; Peng, Wenzhu; Feng, Shuaisheng; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A; Xu, Peng

2016-01-01

The ATP-binding cassette (ABC) gene family is considered to be one of the largest gene families in all forms of prokaryotic and eukaryotic life. Although the ABC transporter genes have been annotated in some species, detailed information about the ABC superfamily and the evolutionary characterization of ABC genes in common carp (Cyprinus carpio) are still unclear. In this research, we identified 61 ABC transporter genes in the common carp genome. Phylogenetic analysis revealed that they could be classified into seven subfamilies, namely 11 ABCAs, six ABCBs, 19 ABCCs, eight ABCDs, two ABCEs, four ABCFs, and 11 ABCGs. Comparative analysis of the ABC genes in seven vertebrate species including common carp, showed that at least 10 common carp genes were retained from the third round of whole genome duplication, while 12 duplicated ABC genes may have come from the fourth round of whole genome duplication. Gene losses were also observed for 14 ABC genes. Expression profiles of the 61 ABC genes in six common carp tissues (brain, heart, spleen, kidney, intestine, and gill) revealed extensive functional divergence among the ABC genes. Different copies of some genes had tissue-specific expression patterns, which may indicate some gene function specialization. This study provides essential genomic resources for future studies in common carp.

Genome-Wide Identification, Characterization and Phylogenetic Analysis of ATP-Binding Cassette (ABC) Transporter Genes in Common Carp (Cyprinus carpio)

Science.gov (United States)

Peng, Wenzhu; Feng, Shuaisheng; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A.

2016-01-01

The ATP-binding cassette (ABC) gene family is considered to be one of the largest gene families in all forms of prokaryotic and eukaryotic life. Although the ABC transporter genes have been annotated in some species, detailed information about the ABC superfamily and the evolutionary characterization of ABC genes in common carp (Cyprinus carpio) are still unclear. In this research, we identified 61 ABC transporter genes in the common carp genome. Phylogenetic analysis revealed that they could be classified into seven subfamilies, namely 11 ABCAs, six ABCBs, 19 ABCCs, eight ABCDs, two ABCEs, four ABCFs, and 11 ABCGs. Comparative analysis of the ABC genes in seven vertebrate species including common carp, showed that at least 10 common carp genes were retained from the third round of whole genome duplication, while 12 duplicated ABC genes may have come from the fourth round of whole genome duplication. Gene losses were also observed for 14 ABC genes. Expression profiles of the 61 ABC genes in six common carp tissues (brain, heart, spleen, kidney, intestine, and gill) revealed extensive functional divergence among the ABC genes. Different copies of some genes had tissue-specific expression patterns, which may indicate some gene function specialization. This study provides essential genomic resources for future studies in common carp. PMID:27058731