Human-directed aggression in the cat.

PubMed

Curtis, Terry Marie

2008-09-01

Feline aggression-between cats or directed at humans-is, after inappropriate elimination and urine-marking behaviors, the second most common reason cats are seen by behavioral specialists. For diagnosis and treatment it is important to determine the motivation for the aggression. The more common causes for human-directed aggression in cats include play, fear, petting intolerance, and redirected aggression. Other causes include pain and maternal behavior. Sexually motivated and status related aggression are much more rare. Treatment includes a combination of behavioral modification, environmental modification, and, in some cases, medication.

REDUCING DIESEL NOX AND SOOT EMISSIONS VIA PARTICLE-FREE EXHAUST GAS RECIRCULATION - PHASE I

EPA Science Inventory

Diesel engines play an important role in the United States economy for power generation and transportation. However, NOx and soot emissions from both stationary and mobile diesel engines are a major contributor to air pollution. Many engine modifications and exhaust-after-t...

Monotopic modifications derived from in vitro glycation of albumin with ribose.

PubMed

Pataridis, Statis; Stastná, Zdeňka; Sedláková, Pavla; Mikšík, Ivan

2013-06-01

Post-translational modifications are significant reactions that occur to proteins. One of these modifications is a non-enzymatic reaction between the oxo-group(s) of sugars and amino-group(s) of protein - glycation. This reaction plays an important role in the chronic complications of diabetes mellitus, or in the aging process of organisms, that is, it has an important role in the pathophysiology and "normal" physiology of animals. In the work presented here, we studied the glycation of albumins (HSA and BSA). Methodologically, we used nano-LC coupled to a QTOF mass spectrometer. In vitro-modified proteins were cleaved by trypsin and the arising peptides were separated on a C(18) nano column with a trap-column. Peptides and their modifications were analysed with a high-resolution QTOF mass spectrometer with a mass determination precision of better than 5 ppm. Non-enzymatic in vitro reaction products between albumin and ribose were identified. Besides well-known carboxymethyl lysine, new modifications were determined - creating mass shifts of 78 and 218. The origin of the first modification is discussed and its possible structure is presented. In addition, a mass shift of 132 belonging to a Schiff base was also identified. The location of all the modifications within the structure of the proteins was determined and their reactivity to various oxo-compounds was also examined. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Repetitive sequences and epigenetic modification: inseparable partners play important roles in the evolution of plant sex chromosomes.

PubMed

Li, Shu-Fen; Zhang, Guo-Jun; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

2016-05-01

The present review discusses the roles of repetitive sequences played in plant sex chromosome evolution, and highlights epigenetic modification as potential mechanism of repetitive sequences involved in sex chromosome evolution. Sex determination in plants is mostly based on sex chromosomes. Classic theory proposes that sex chromosomes evolve from a specific pair of autosomes with emergence of a sex-determining gene(s). Subsequently, the newly formed sex chromosomes stop recombination in a small region around the sex-determining locus, and over time, the non-recombining region expands to almost all parts of the sex chromosomes. Accumulation of repetitive sequences, mostly transposable elements and tandem repeats, is a conspicuous feature of the non-recombining region of the Y chromosome, even in primitive one. Repetitive sequences may play multiple roles in sex chromosome evolution, such as triggering heterochromatization and causing recombination suppression, leading to structural and morphological differentiation of sex chromosomes, and promoting Y chromosome degeneration and X chromosome dosage compensation. In this article, we review the current status of this field, and based on preliminary evidence, we posit that repetitive sequences are involved in sex chromosome evolution probably via epigenetic modification, such as DNA and histone methylation, with small interfering RNAs as the mediator.

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

PubMed Central

Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

2017-01-01

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD. PMID:28966576

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer's Disease.

PubMed

Wang, Xin; Zhou, Xuan; Li, Gongying; Zhang, Yun; Wu, Yili; Song, Weihong

2017-01-01

Alzheimer's disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD.

Detection of histone modifications in plant leaves.

PubMed

Jaskiewicz, Michal; Peterhansel, Christoph; Conrath, Uwe

2011-09-23

Chromatin structure is important for the regulation of gene expression in eukaryotes. In this process, chromatin remodeling, DNA methylation, and covalent modifications on the amino-terminal tails of histones H3 and H4 play essential roles(1-2). H3 and H4 histone modifications include methylation of lysine and arginine, acetylation of lysine, and phosphorylation of serine residues(1-2). These modifications are associated either with gene activation, repression, or a primed state of gene that supports more rapid and robust activation of expression after perception of appropriate signals (microbe-associated molecular patterns, light, hormones, etc.)(3-7). Here, we present a method for the reliable and sensitive detection of specific chromatin modifications on selected plant genes. The technique is based on the crosslinking of (modified) histones and DNA with formaldehyde(8,9), extraction and sonication of chromatin, chromatin immunoprecipitation (ChIP) with modification-specific antibodies(9,10), de-crosslinking of histone-DNA complexes, and gene-specific real-time quantitative PCR. The approach has proven useful for detecting specific histone modifications associated with C(4;) photosynthesis in maize(5,11) and systemic immunity in Arabidopsis(3).

Epigenetics of the antibody response

PubMed Central

Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

2013-01-01

Epigenetic marks, such as DNA methylation, histone posttranslational modifications and microRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR) and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and microRNAs modulate the expression of critical elements of that machinery, such as AID, as well as factors central to plasma cell differentiation, such as Blimp-1. These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such those targeted in autoimmunity, and B cell neoplasias. PMID:23643790

NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms.

PubMed

Liao, Xing-Hua; Wang, Nan; Zhao, Dong-Wei; Zheng, De-Liang; Zheng, Li; Xing, Wen-Jing; Zhou, Hao; Cao, Dong-Sun; Zhang, Tong-Cun

2014-12-01

Myocardin is well known to play a key role in the development of cardiomyocyte hypertrophy. But the exact molecular mechanism regulating myocardin stability and transactivity to affect cardiomyocyte hypertrophy has not been studied clearly. We now report that NF-κB (p65) can inhibit myocardin-induced cardiomyocyte hypertrophy. Then we explore the molecular mechanism of this response. First, we show that p65 can functionally repress myocardin transcriptional activity and also reduce the protein expression of myocardin. Second, the function of myocardin can be regulated by epigenetic modifications. Myocardin sumoylation is known to transactivate cardiac genes, but whether p65 can inhibit SUMO modification of myocardin is still not clear. Our data show that p65 weakens myocardin transcriptional activity through attenuating SUMO modification of myocardin by SUMO1/PIAS1, thereby impairing myocardin-mediated cardiomyocyte hypertrophy. Furthermore, the expression of myocardin can be regulated by several microRNAs, which play important roles in the development and function of the heart and muscle. We next investigated potential role of miR-1 in cardiac hypotrophy. Our results show that p65 can upregulate the level of miR-1 and miR-1 can decrease protein expression of myocardin in cardiac myocytes. Notably, miR-1 expression is also controlled by myocardin, leading to a feedback loop. These data thus provide important and novel insights into the function that p65 inhibits myocardin-mediated cardiomyocyte hypertrophy by downregulating the expression and SUMO modification of myocardin and enhancing the expression of miR-1. Copyright © 2014 Elsevier Inc. All rights reserved.

Epigenetic dynamics in psychiatric disorders: environmental programming of neurodevelopmental processes.

PubMed

Kofink, Daniel; Boks, Marco P M; Timmers, H T Marc; Kas, Martien J

2013-06-01

Epigenetic processes have profound influence on gene translation and play a key role in embryonic development and tissue type specification. Recent advances in our understanding of epigenetics have pointed out that epigenetic alterations also play an important role in neurodevelopment and may increase the risk to psychiatric disorders. In addition to genetic regulation of these processes, compelling evidence suggests that environmental conditions produce persistent changes in development through epigenetic mechanisms. Adverse environmental influences in early life such as maternal care, alcohol exposure and prenatal nutrition interact with epigenetic factors and may induce neurodevelopmental disturbances that are related to psychiatric disorders. This review outlines recent findings linking environmentally induced modifications of the epigenome to brain development and psychopathology. Better understanding of these modifications is relevant from the perspective that they may be reversible and, therefore, offer potential for novel treatment strategies. We present the current state of knowledge and show that integrative approaches are necessary to further understand the causal pathways between environmental influences, epigenetic modification, and neuronal function. Copyright © 2013 Elsevier Ltd. All rights reserved.

RUNX family members are covalently modified and regulated by PIAS1-mediated sumoylation

PubMed Central

Kim, J-H; Jang, J-W; Lee, Y-S; Lee, J-W; Chi, X-Z; Li, Y-H; Kim, M-K; Kim, D-M; Choi, B-S; Kim, J; Kim, H-M; van Wijnen, A; Park, IlY; Bae, S-C

2014-01-01

Transcription factors of the RUNX family (RUNXs), which play pivotal roles in normal development and neoplasia, are regulated by various post-translational modifications. To understand the molecular mechanisms underlying the regulation of RUNXs, we performed a large-scale functional genetic screen of a fly mutant library. The screen identified dPias (the fly ortholog of mammalian PIASs), an E3 ligase for the SUMO (small ubiquitin-like modifier) modification, as a novel genetic modifier of lz (the fly ortholog of mammalian RUNX3). Molecular biological analysis revealed that lz/RUNXs are sumoylated by dPias/PIAS1 at an evolutionarily conserved lysine residue (K372 of lz, K144 of RUNX1, K181 of RUNX2 and K148 of RUNX3). PIAS1-mediated sumoylation inhibited RUNX3 transactivation activity, and this modification was promoted by the AKT1 kinase. Importantly, PIAS1 failed to sumoylate some RUNX1 mutants associated with breast cancer. In nude mice, tumorigenicity was promoted by RUNX3 bearing a mutation in the sumoylation site, but suppressed by wild-type RUNX3. Our results suggest that RUNXs are sumoylated by PIAS1, and that this modification could play a critical role in the regulation of the tumor-suppressive activity of these proteins. PMID:24777122

Reshaping of Coastlines as the Beginning of Urban Structures Changes in North Poland

NASA Astrophysics Data System (ADS)

Burda, Izabela M.; Nyka, Lucyna; Borodziuk, Adam

2017-10-01

This article discusses the problem of strategies concerning the processes of re-shaping the Baltic Sea southern coastline applied recently in North Poland. The undertaken research is an attempt to identify the relationship between the modifications of coastline forms and the positive changes of urban structures. First of all, it can be seen that these modifications are needed because of the problems of existing shoreline erosion. It can be also observed, that many realized interventions were helpful to save the land but they did not improve the condition of cities situated along the coast. In these cases, it is impossible to connect the sea coastline with the existing grid of public spaces which is a barrier to creating a system that could be perceived as a coherent landscape. The basis for proving the importance of special ways of shoreline modifications are comparative studies and in-field analyses. In facing the problems of coastal cities there is a need to analyse the condition of existing urban structures. Many studies made so far show that there are many problems which have to be identified and solved. Worth noting is the fact that these structures have a unique character because of their location. They play an important role as holiday resorts being an attraction for many inhabitants and visitors from all over the world. Such a role plays, for example, an important part in places such as Jarosławiec, Ustka or Kołobrzeg. However, analysing the strategies applied in recent years, it can be noted that they cannot be the only basis for the strengthening of connections between land and water helping to preserve the land, but they may also play an important role as a factor for initiating urban structures transformations. What is also important, it can be claimed that relationships between sea water and urban structures should be strengthened due to special forms of the coast line. They should be integrated into existing structures making them more comfortable and attractive while also protecting against threats from the water. Playing the role as a protector of land they should use special constructions being at the same time accessible to all users throughout the year and regardless of weather conditions. It is worth emphasizing that special treatment of the coastline helps to establish it as a public domain which is important in achieving high quality urban-water landscapes. Therefore it should be the objective of strategies which are being prepared for parts of coastlines waiting for intervention.

Analysis of sDMA modifications of PIWI proteins

PubMed Central

Honda, Shozo; Kirino, Yoriko; Kirino, Yohei

2015-01-01

Summary Arginine methylation is an important post-translational protein modification that modulates protein function for a wide range of biological processes. PIWI proteins, a subclade of the Argonaute family proteins, contain evolutionarily conserved symmetrical dimethylarginines (sDMAs). It has become increasingly apparent that the sDMAs of PIWI proteins serve as binding elements for TUDOR-domain containing proteins and that sDMA-dependent protein interactions play crucial roles in the biogenesis and function of PIWI-interacting RNAs (piRNAs). We describe a method for detecting PIWI sDMAs and purifying PIWI/piRNA complexes using anti-sDMA antibodies. PMID:24178562

Changes in cell wall polysaccharide composition, gene transcription and alternative splicing in germinating barley embryos.

PubMed

Zhang, Qisen; Zhang, Xiaoqi; Pettolino, Filomena; Zhou, Gaofeng; Li, Chengdao

2016-02-01

Barley (Hordeum vulgare L.) seed germination initiates many important biological processes such as DNA, membrane and mitochondrial repairs. However, little is known on cell wall modifications in germinating embryos. We have investigated cell wall polysaccharide composition change, gene transcription and alternative splicing events in four barley varieties at 24h and 48 h germination. Cell wall components in germinating barley embryos changed rapidly, with increases in cellulose and (1,3)(1,4)-β-D-glucan (20-100%) within 24h, but decreases in heteroxylan and arabinan (3-50%). There were also significant changes in the levels of type I arabinogalactans and heteromannans. Alternative splicing played very important roles in cell wall modifications. At least 22 cell wall transcripts were detected to undergo either alternative 3' splicing, alternative 5' splicing or intron retention type of alternative splicing. These genes coded enzymes catalyzing synthesis and degradation of cellulose, heteroxylan, (1,3)(1,4)-β-D-glucan and other cell wall polymers. Furthermore, transcriptional regulation also played very important roles in cell wall modifications. Transcript levels of primary wall cellulase synthase, heteroxylan synthesizing and nucleotide sugar inter-conversion genes were very high in germinating embryos. At least 50 cell wall genes changed transcript levels significantly. Expression patterns of many cell wall genes coincided with changes in polysaccharide composition. Our data showed that cell wall polysaccharide metabolism was very active in germinating barley embryos, which was regulated at both transcriptional and post-transcriptional levels. Copyright © 2015 Elsevier GmbH. All rights reserved.

Polymicrobial infection and bacterium-mediated epigenetic modification of DNA tumor viruses contribute to pathogenesis.

PubMed

Doolittle, J M; Webster-Cyriaque, J

2014-04-29

ABSTRACT The human body plays host to a wide variety of microbes, commensal and pathogenic. In addition to interacting with their host, different microbes, such as bacteria and viruses, interact with each other, sometimes in ways that exacerbate disease. In particular, gene expression of a number of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), is known to be regulated by epigenetic modifications induced by bacteria. These viruses establish latent infection in their host cells and can be reactivated by bacterial products. Viral reactivation has been suggested to contribute to periodontal disease and AIDS. In addition, bacterium-virus interactions may play a role in cancers, such as Kaposi's sarcoma, gastric cancer, and head and neck cancer. It is important to consider the effects of coexisting bacterial infections when studying viral diseases in vivo.

Complex Relationships Between Food, Diet and the Microbiome

PubMed Central

Pace, Laura A.; Crowe, Sheila E.

2018-01-01

Diet is a risk factor in a number of medically important disease states including obesity, celiac disease and functional gastrointestinal disorders. Modification of diet can prevent, treat or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations in order to increase the probability of successful implementation. These include increasing vegetable, fruit and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients. Women can play an important role in maintaining family health by making more informed dietary decisions. The gut microbiome may play a role in some gastrointestinal disorders. However better designed studies are required to differentiate correlation from causation in this emerging area. PMID:27261897

Environmental Gerontology at the Beginning of the New Millennium: Reflections on Its Historical, Empirical, and Theoretical Development

ERIC Educational Resources Information Center

Wahl, Hans-Werner; Weisman, Gerald D.

2003-01-01

Over the past four decades the environmental context of aging has come to play an important role in gerontological theory, research, and practice. Environmental gerontology (EG)--focused on the description, explanation, and modification or optimization of the relation between elderly persons and their sociospatial surroundings--has emerged as a…

Communication in Development: Modifications in the Classical Diffusion Model for Family Planning.

ERIC Educational Resources Information Center

Rogers, Everett M.

The role of mass media and interpersonal communication in development in Latin America, Africa, and Asia is reviewed. Then, research and development program experience is synthesized to show (1) that the mass media at present play a major role in creating a "climate for modernization" among villagers, but are less important in diffusing…

Epigenetics in the Vascular Endothelium: Looking From a Different Perspective in the Epigenomics Era.

PubMed

Yan, Matthew S; Marsden, Philip A

2015-11-01

Cardiovascular diseases are commonly thought to be complex, non-Mendelian diseases that are influenced by genetic and environmental factors. A growing body of evidence suggests that epigenetic pathways play a key role in vascular biology and might be involved in defining and transducing cardiovascular disease inheritability. In this review, we argue the importance of epigenetics in vascular biology, especially from the perspective of endothelial cell phenotype. We highlight and discuss the role of epigenetic modifications across the transcriptional unit of protein-coding genes, especially the role of intragenic chromatin modifications, which are underappreciated and not well characterized in the current era of genome-wide studies. Importantly, we describe the practical application of epigenetics in cardiovascular disease therapeutics. © 2015 American Heart Association, Inc.

The story of protein arginine methylation: characterization, regulation, and function.

PubMed

Peng, Chao; Wong, Catherine Cl

2017-02-01

Arginine methylation is an important post-translational modification (PTM) in cells, which is catalyzed by a group of protein arginine methyltransferases (PRMTs). It plays significant roles in diverse cellular processes and various diseases. Misregulation and aberrant expression of PRMTs can provide potential biomarkers and therapeutic targets for drug discovery. Areas covered: Herein, we review the arginine methylation literature and summarize the methodologies for the characterization of this modification, as well as describe the recent insights into arginine methyltransferases and their biological functions in diseases. Expert commentary: Benefits from the enzyme-based large-scale screening approach, the novel affinity enrichment strategies, arginine methylated protein family is the focus of attention. Although a number of arginine methyltransferases and related substrates are identified, the catalytic mechanism of different types of PRMTs remains unclear and few related demethylases are characterized. Novel functional studies continuously reveal the importance of this modification in the cell cycle and diseases. A deeper understanding of arginine methylated proteins, modification sites, and their mechanisms of regulation is needed to explore their role in life processes, especially their relationship with diseases, thus accelerating the generation of potent, selective, cell-penetrant drug candidates.

Epigenetic Control of Cytokine Gene Expression: Regulation of the TNF/LT Locus and T Helper Cell Differentiation

PubMed Central

Falvo, James V.; Jasenosky, Luke D.; Kruidenier, Laurens; Goldfeld, Anne E.

2014-01-01

Epigenetics encompasses transient and heritable modifications to DNA and nucleosomes in the native chromatin context. For example, enzymatic addition of chemical moieties to the N-terminal “tails” of histones, particularly acetylation and methylation of lysine residues in the histone tails of H3 and H4, plays a key role in regulation of gene transcription. The modified histones, which are physically associated with gene regulatory regions that typically occur within conserved noncoding sequences, play a functional role in active, poised, or repressed gene transcription. The “histone code” defined by these modifications, along with the chromatin-binding acetylases, deacetylases, methylases, demethylases, and other enzymes that direct modifications resulting in specific patterns of histone modification, shows considerable evolutionary conservation from yeast to humans. Direct modifications at the DNA level, such as cytosine methylation at CpG motifs that represses promoter activity, are another highly conserved epigenetic mechanism of gene regulation. Furthermore, epigenetic modifications at the nucleosome or DNA level can also be coupled with higher-order intra- or interchromosomal interactions that influence the location of regulatory elements and that can place them in an environment of specific nucleoprotein complexes associated with transcription. In the mammalian immune system, epigenetic gene regulation is a crucial mechanism for a range of physiological processes, including the innate host immune response to pathogens and T cell differentiation driven by specific patterns of cytokine gene expression. Here, we will review current findings regarding epigenetic regulation of cytokine genes important in innate and/or adaptive immune responses, with a special focus upon the tumor necrosis factor/lymphotoxin locus and cytokine-driven CD4+ T cell differentiation into the Th1, Th2, and Th17 lineages. PMID:23683942

Regulation of the Hippo signaling pathway by ubiquitin modification.

PubMed

Kim, Youngeun; Jho, Eek-Hoon

2018-03-01

The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. β-TrCP is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway. [BMB Reports 2018; 51(3): 143-150].

Nutrition Interventions in Chronic Kidney Disease.

PubMed

Anderson, Cheryl A M; Nguyen, Hoang Anh; Rifkin, Dena E

2016-11-01

Dietary modification is recommended in the management of chronic kidney disease (CKD). Individuals with CKD often have multiple comorbidities, such as high blood pressure, diabetes, obesity, and cardiovascular disease, for which dietary modification is also recommended. As CKD progresses, nutrition plays an important role in mitigating risk for cardiovascular disease and decline in kidney function. The objectives of nutrition interventions in CKD include management of risk factors, ensuring optimal nutritional status throughout all stages of CKD, preventing buildup of toxic metabolic products, and avoiding complications of CKD. Recommended dietary changes should be feasible, sustainable, and suited for patients' food preferences and clinical needs. Copyright © 2016 Elsevier Inc. All rights reserved.

Parenting Strains, Distress, and Family Paid Labor: A Modification of the Cost-of-Caring Hypothesis

ERIC Educational Resources Information Center

Roxburgh, Susan

2005-01-01

Parenting strains are an important dimension of the parenting experience with significant implications for well-being. The cost-of-caring hypothesis suggests that mothers will be more adversely affected by parenting strains. In light of mixed support for the cost-of-caring hypothesis, the author argues that other social contexts may play a role in…

Design and Implementation of 3D Model Data Management System Based on SQL

NASA Astrophysics Data System (ADS)

Li, Shitao; Zhang, Shixin; Zhang, Zhanling; Li, Shiming; Jia, Kun; Hu, Zhongxu; Ping, Liang; Hu, Youming; Li, Yanlei

CAD/CAM technology plays an increasingly important role in the machinery manufacturing industry. As an important means of production, the accumulated three-dimensional models in many years of design work are valuable. Thus the management of these three-dimensional models is of great significance. This paper gives detailed explanation for a method to design three-dimensional model databases based on SQL and to implement the functions such as insertion, modification, inquiry, preview and so on.

Hydrothermal calcium modification of 316L stainless steel and its apatite forming ability in simulated body fluid.

PubMed

Valanezahad, Alireza; Ishikawa, Kunio; Tsuru, Kanji; Maruta, Michito; Matsuya, Shigeki

2011-01-01

To understand the feasibility of calcium (Ca) modification of type 316L stainless steel (316L SS) surface using hydrothermal treatment, 316L SS plates were treated hydrothermally in calcium chloride (CaCl(2)) solution. X-ray photoelectron spectroscopic analysis revealed that the surface of 316L SS plate was modified with Ca after hydrothermal treatment at 200°C. And the immobilized Ca increased with CaCl(2) concentration. However no Ca-modification was occurred for 316L SS plates treated at 100°C. When Ca-modified 316L SS plate was immersed in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma, low crystalline apatite was precipitated on its surface whereas no precipitate was observed on non Ca-modified 316L SS. The results obtained in the present study indicated that hydrothermal treatment at 200°C in CaCl(2) solution is useful for Ca-modification of 316L SS, and Ca-modification plays important role for apatite precipitation in SBF.

Purification of CFTR for mass spectrometry analysis: identification of palmitoylation and other post-translational modifications

PubMed Central

McClure, Michelle; DeLucas, Lawrence J.; Wilson, Landon; Ray, Marjorie; Rowe, Steven M.; Wu, Xiaoyun; Dai, Qun; Hong, Jeong S.; Sorscher, Eric J.; Kappes, John C.; Barnes, Stephen

2012-01-01

Post-translational modifications (PTMs) play a crucial role during biogenesis of many transmembrane proteins. Previously, it had not been possible to evaluate PTMs in cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial ion channel responsible for cystic fibrosis, because of difficulty obtaining sufficient amounts of purified protein. We recently used an inducible overexpression strategy to generate recombinant CFTR protein at levels suitable for purification and detailed analysis. Using liquid chromatography (LC) tandem and multiple reaction ion monitoring (MRM) mass spectrometry, we identified specific sites of PTMs, including palmitoylation, phosphorylation, methylation and possible ubiquitination. Many of these covalent CFTR modifications have not been described previously, but are likely to influence key and clinically important molecular processes including protein maturation, gating and the mechanisms underlying certain mutations associated with disease. PMID:22119790

Epigenetics and maternal nutrition: nature v. nurture.

PubMed

Simmons, Rebecca

2011-02-01

Under- and over-nutrition during pregnancy has been linked to the later development of diseases such as diabetes and obesity. Epigenetic modifications may be one mechanism by which exposure to an altered intrauterine milieu or metabolic perturbation may influence the phenotype of the organism much later in life. Epigenetic modifications of the genome provide a mechanism that allows the stable propagation of gene expression from one generation of cells to the next. This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodelling and histone modifications play key roles in adipogenesis and the development of obesity. Epigenetic modifications affecting processes important to glucose regulation and insulin secretion have been described in the pancreatic β-cells and muscle of the intrauterine growth-retarded offspring, characteristics essential to the pathophysiology of type-2 diabetes. Epigenetic regulation of gene expression contributes to both adipocyte determination and differentiation in in vitro models. The contributions of histone acetylation, histone methylation and DNA methylation to the process of adipogenesis in vivo remain to be evaluated.

Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.

PubMed

Li, Nan; Stein, Richard S L; He, Wei; Komives, Elizabeth; Wang, Wei

2013-10-01

Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein-protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure modeling, bioinformatics analysis, and peptide microarray experiments to identify lysine residues that are methylated and recognized by the chromodomain in the human proteome. Given the important role of chromobox protein homolog 6 as a reader of histone modifications, it was interesting to find that the majority of its interacting partners identified via this approach function in chromatin remodeling and transcriptional regulation. Our study not only illustrates a novel angle for identifying methyllysines on a proteome-wide scale and elucidating their potential roles in regulating protein function, but also suggests possible strategies for engineering the chromodomain-peptide interface to enhance the recognition of and manipulate the signal transduction mediated by such interactions.

Epigenetics and type II diabetes mellitus: underlying mechanisms of prenatal predisposition

PubMed Central

Sterns, J. David; Smith, Colin B.; Steele, John R.; Stevenson, Kimberly L.; Gallicano, G. Ian

2014-01-01

Type II diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance precipitating abnormally high blood glucose levels. While the onset of T2DM is known to be the consequence of a multifactorial interplay with a strong genetic component, emerging research has demonstrated the additional role of a variety of epigenetic mechanisms in the development of this disorder. Heritable epigenetic modifications, such as DNA methylation and histone modifications, play a vital role in many important cellular processes, including pancreatic cellular differentiation and maintenance of normal β-cell function. Recent studies have found possible epigenetic mechanisms to explain observed risk factors, such as altered atherogenic lipid profiles, elevated body mass index (BMI), and impaired glucose tolerance (IGT), for later development of T2DM in children born to mothers experiencing both famine and hyperglycemic conditions. It is suggested that these epigenetic influences happen early during gestation and are less susceptible to the effects of postnatal environmental modification as was previously thought, highlighting the importance of early preventative measures in minimizing the global burden of T2DM. PMID:25364722

Histone Arginine Methylation

PubMed Central

Lorenzo, Alessandra Di; Bedford, Mark T.

2012-01-01

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code. PMID:21074527

Food and Growth. Seychelles Integrated Science. [Teacher and Pupil Booklets]. Unit 7.

ERIC Educational Resources Information Center

Brophy, M.; Fryars, M.

Seychelles Integrated Science (SIS), a 3-year laboratory-based science program for students (ages 11-15) in upper primary grades 7, 8, and 9, was developed from an extensive evaluation and modification of previous P7-P9 materials. This P8 SIS unit examines: (1) the role played by bones, muscles, and teeth and the importance of developing and…

Epigenetic Modifications of Major Depressive Disorder

PubMed Central

Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

2016-01-01

Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

Significance of the Eccentricity of the Earth's Magnetic Field for the Magnetosphere and Ionospheric Modification

NASA Astrophysics Data System (ADS)

Koochak, Z.; Fraser-Smith, A. C.

2016-12-01

This paper is an extension of an earlier study of the centered and eccentric dipole models of the Earth's magnetic field [Fraser-Smith, 1987]. We have used the 1980-2015 International Geomagnetic Reference Field (IGRF) Gauss coefficients to recalculate the magnetic dipole moments and magnetic pole positions for both the centered and eccentric dipoles for an additional 35 years, thus bringing them up to date. These magnetic field models play an important role in ionosphere modification, since they influence the properties of the ionosphere. However it is not widely known that the nominal origin of the Earth's magnetic field is offset from the center of the Earth by nearly 10% of the Earth's radius, which must similarly lead to an offset of some of the larger-scale modifying effects such as those associated with the magnetosphere. We describe this offset magnetic field here to help identify its effects in ionospheric modification experiments.

Dynamics of gene expression with positive feedback to histone modifications at bivalent domains

NASA Astrophysics Data System (ADS)

Huang, Rongsheng; Lei, Jinzhi

2018-03-01

Experiments have shown that in embryonic stem cells, the promoters of many lineage-control genes contain “bivalent domains”, within which the nucleosomes possess both active (H3K4me3) and repressive (H3K27me3) marks. Such bivalent modifications play important roles in maintaining pluripotency in embryonic stem cells. Here, to investigate gene expression dynamics when there are regulations in bivalent histone modifications and random partition in cell divisions, we study how positive feedback to histone methylation/demethylation controls the transition dynamics of the histone modification patterns along with cell cycles. We constructed a computational model that includes dynamics of histone marks, three-stage chromatin state transitions, transcription and translation, feedbacks from protein product to enzymes to regulate the addition and removal of histone marks, and the inheritance of nucleosome state between cell cycles. The model reveals how dynamics of both nucleosome state transition and gene expression are dependent on the enzyme activities and feedback regulations. Results show that the combination of stochastic histone modification at each cell division and the deterministic feedback regulation work together to adjust the dynamics of chromatin state transition in stem cell regenerations.

Research on the Management Training, and Utilization of Low-Aptitude Personnel: An Annotated Bibliography

DTIC Science & Technology

1976-12-01

intercorrelated, resulting in several significant relationships involving verbal andtarithmetic skills , particularly the AFQT, GCT, ARI, and the Navy Literacy ...training in literacy and basic arithmetic skills for Category IV personnel would play a role at least as important as course modifications. When... relationship between reading level and performance is, at best, only partially uncovered. Other studies have dealt with concerns related to literacy but

Widespread occurrence of lysine methylation in Plasmodium falciparum proteins at asexual blood stages.

PubMed

Kaur, Inderjeet; Zeeshan, Mohammad; Saini, Ekta; Kaushik, Abhinav; Mohmmed, Asif; Gupta, Dinesh; Malhotra, Pawan

2016-10-20

Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites. Using liquid chromatography and tandem mass spectrometry analysis, 570 lysine methylated proteins at three different blood stages were identified. Analysis of the peptide sequences identified 605 methylated sites within 422 proteins. Functional classification of the methylated proteins revealed that the proteins are mainly involved in nucleotide metabolic processes, chromatin organization, transport, homeostatic processes and protein folding. The motif analysis of the methylated lysine peptides reveals novel motifs. Many of the identified lysine methylated proteins are also interacting partners/substrates of PfSET domain proteins as revealed by STRING database analysis. Our findings suggest that the protein methylation at lysine residues is widespread in Plasmodium and plays an important regulatory role in diverse set of the parasite pathways.

Comprehensive Analysis of Protein Modifications by Top-down Mass Spectrometry

PubMed Central

Zhang, Han; Ge, Ying

2012-01-01

Mass spectrometry (MS)-based proteomics is playing an increasingly important role in cardiovascular research. Proteomics includes not only identification and quantification of proteins, but also the characterization of protein modifications such as post-translational modifications and sequence variants. The conventional bottom-up approach, involving proteolytic digestion of proteins into small peptides prior to MS analysis, is routinely used for protein identification and quantification with high throughput and automation. Nevertheless, it has limitations in the analysis of protein modifications mainly due to the partial sequence coverage and loss of connections among modifications on disparate portions of a protein. An alternative approach, top-down MS, has emerged as a powerful tool for the analysis of protein modifications. The top-down approach analyzes whole proteins directly, providing a “bird’s eye” view of all existing modifications. Subsequently, each modified protein form can be isolated and fragmented in the mass spectrometer to locate the modification site. The incorporation of the non-ergodic dissociation methods such as electron capture dissociation (ECD) greatly enhances the top-down capabilities. ECD is especially useful for mapping labile post-translational modifications which are well-preserved during the ECD fragmentation process. Top-down MS with ECD has been successfully applied to cardiovascular research with the unique advantages in unraveling the molecular complexity, quantifying modified protein forms, complete mapping of modifications with full sequence coverage, discovering unexpected modifications, and identifying and quantifying positional isomers and determining the order of multiple modifications. Nevertheless, top-down MS still needs to overcome some technical challenges to realize its full potential. Herein, we reviewed the advantages and challenges of top-down methodology with a focus on its application in cardiovascular research. PMID:22187450

FIBER OPTICS: Role of point defects in the photosensitivity of hydrogen-loaded phosphosilicate glass

NASA Astrophysics Data System (ADS)

Larionov, Yu V.

2010-08-01

It is shown that point defect modifications in hydrogen-loaded phosphosilicate glass (PSG) do not play a central role in determining its photosensitivity. Photochemical reactions that involve a two-step point defect modification and pre-exposure effect are incapable of accounting for photoinduced refractive index changes. It seems likely that a key role in UV-induced refractive index modifications is played by structural changes in the PSG network. Experimental data are presented that demonstrate intricate network rearrangement dynamics during UV exposure of PSG.

Channeling techniques to study strains and defects in heterostructures and multi quantum wells

NASA Astrophysics Data System (ADS)

Pathak, A. P.; Dhamodaran, S.; Sathish, N.

2005-08-01

The importance and advantages of heterostructures and Quantum Wells (QWs) in device technology has made research challenging due to lack of direct techniques for their characterization. Particularly the characterization of strain and defects at the interfaces has become important due to their dominance in the electrical and optical properties of materials and devices. RBSiC has been used to study variety of defects in single crystalline materials, for nearly four decades now. Channeling based experiments play a crucial role in giving depth information of strain and defects. Ion beams are used for both material characterizations as well as for modifications. Hence it is also possible to monitor the modifications online, which are discussed in detail. In the present work, Swift Heavy Ion (SHI) modification of III-V semiconductor heterostnictures and MQWs and the results of subsequent strain measurements by RBSiC in initially strained as well as lattice matched systems are discussed. We find that the compressive strain decreases due to SHI irradiation and a tensile strain is induced in an initially lattice matched system. The incident ion fluence dependence of strain modifications in the heterostructures will also be discussed. The use of high energy channeling for better sensitivity of strain measurements in low mismatch materials will be discussed in detail. Wherever possible, a comparison of results with those obtained by other techniques like HRXRD is given.

Manipulation of the swirling flow instability in hydraulic turbine diffuser by different methods of water injection

NASA Astrophysics Data System (ADS)

Rudolf, Pavel; Litera, Jiří; Alejandro Ibarra Bolanos, Germán; Štefan, David

2018-06-01

Vortex rope, which induces substantial pressure pulsations, arises in the draft tube (diffuser) of Francis turbine for off-design operating conditions. Present paper focuses on mitigation of those pulsations using active water jet injection control. Several modifications of the original Susan-Resiga's idea were proposed. All modifications are driven by manipulation of the shear layer region, which is believed to play important role in swirling flow instability. While some of the methods provide results close to the original one, none of them works in such a wide range. Series of numerical experiments support the idea that the necessary condition for vortex rope pulsation mitigation is increasing the fluid momentum along the draft tube axis.

Aflatoxin B1-induced epigenetic alterations: An overview.

PubMed

Dai, Yaqi; Huang, Kunlun; Zhang, Boyang; Zhu, Liye; Xu, Wentao

2017-11-01

Aflatoxin B1 (AFB1) is widely distributed in nature, especially in a variety of food commodities. It is confirmed to be the most toxic of all the aflatoxins. The toxicity of AFB1 has been well investigated, and it may result in severe health problems including carcinogenesis, mutagenesis, growth retardation, and immune suppression. Epigenetic modifications including DNA methylation, histone modifications and regulation of non-coding RNA play an important role in AFB1-induced disease and carcinogenesis. To better understand the evidence for AFB1-induced epigenetic alterations and the potential mechanisms of the toxicity of AFB1, we conducted a review of published studies of AFB1-induced epigenetic alterations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutrition in early life and the programming of adult disease: the first 1000 days

PubMed

Moreno Villares, José Manuel

2016-07-12

Development during fetal life and infancy is characterized by rapid growth as well as the maturation of organs and systems. Changes, both in quality and quality, in nutrients during these periods may permanently infl uence the way these organs mature and function. These effects are termed as “programming” and play an important role in the presence of non-transmissible diseases through the lifespan. Specially cardiovascular disease, metabolic disorders and carbohydrate intolerance. Nutritional deficits during pregnancy, leading to intrauterine growth restriction, are associated to a higher risk of type 2 diabetes, and coronary disease among the offspring. This infl uence does not stop with the delivery but early nutrition in infancy, type of lactation, and the way and time solid foods are introduced, does play a role in this programming. Nutritional and non-nutritional factors alter the expression of some genes, resulting in effective remodeling of tissue structure and functionality. These epigenetic modifications can be transmitted to further generations, adding evidence that hereditable epigenetic modifications play a critical role in nutritional programming. But, at the same time, it opens a window of opportunity to decrease the burden of non-transmissible disease by a clever advise on nutrition during pregnancy and across the first 2 years of life (the so-called 1000 days strategy).

Foreword

NASA Astrophysics Data System (ADS)

Bergheau, Jean-Michel; Drapier, Sylvain; Feulvarch, Éric; Ponthot, Jean-Philippe

2016-04-01

In the face of increasingly fierce global competition, industrial companies must develop products more and more quickly and cheaply. In such a context, the numerical simulation of manufacturing processes is a big challenge and a key factor for success. Indeed, numerical simulation enables the control of manufacturing processes and of the consequences that they induce on the manufactured parts in terms of material modifications, geometrical changes or residual stresses, each of them playing an important role in the lifetime of the component.

An efficient immunodetection method for histone modifications in plants.

PubMed

Nic-Can, Geovanny; Hernández-Castellano, Sara; Kú-González, Angela; Loyola-Vargas, Víctor M; De-la-Peña, Clelia

2013-12-16

Epigenetic mechanisms can be highly dynamic, but the cross-talk among them and with the genome is still poorly understood. Many of these mechanisms work at different places in the cell and at different times of organism development. Covalent histone modifications are one of the most complex and studied epigenetic mechanisms involved in cellular reprogramming and development in plants. Therefore, the knowledge of the spatial distribution of histone methylation in different tissues is important to understand their behavior on specific cells. Based on the importance of epigenetic marks for biology, we present a simplified, inexpensive and efficient protocol for in situ immunolocalization on different tissues such as flowers, buds, callus, somatic embryo and meristematic tissue from several plants of agronomical and biological importance. Here, we fully describe all the steps to perform the localization of histone modifications. Using this method, we were able to visualize the distribution of H3K4me3 and H3K9me2 without loss of histological integrity of tissues from several plants, including Agave tequilana, Capsicum chinense, Coffea canephora and Cedrela odorata, as well as Arabidopsis thaliana. There are many protocols to study chromatin modifications; however, most of them are expensive, difficult and require sophisticated equipment. Here, we provide an efficient protocol for in situ localization of histone methylation that dispenses with the use of expensive and sensitive enzymes. The present method can be used to investigate the cellular distribution and localization of a wide array of proteins, which could help to clarify the biological role that they play at specific times and places in different tissues of various plant species.

mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.

PubMed

Visvanathan, Abhirami; Somasundaram, Kumaravel

2018-01-01

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome. © 2017 WILEY Periodicals, Inc.

Structual Effects of Cytidine 2^' Ribose Modifications as Determined by Irmpd Action Spectroscopy

NASA Astrophysics Data System (ADS)

Hamlow, Lucas; He, Chenchen; Fan, Lin; Wu, Ranran; Yang, Bo; Rodgers, M. T.; Berden, Giel; Oomens, J.

2015-06-01

Modified nucleosides, both naturally occurring and synthetic play an important role in understanding and manipulating RNA and DNA. Naturally occurring modified nucleosides are commonly found in functionally important regions of RNA and also affect antibiotic resistance or sensitivity. Synthetic modifications of nucleosides such as fluorinated and arabinosyl nucleosides have found uses as anti-virals and chemotherapy agents. Understanding the effect that modifications have on structure and glycosidic bond stability may lend insight into the functions of these modified nucleosides. Modifications such as the naturally occurring 2^'-O-methylation and the synthetic 2^'-fluorination are believed to help stabilize the nucleoside through the glycosidic bond stability and intramolecular hydrogen bonding. Changing the sugar from ribose to arabinose alters the stereochemistry at the 2^' position and thus shifts the 3D orientation of the 2^'-hydroxyl group, which also affects intramolecular hydrogen bonding and glycosidic bond stability. The structures of 2^'-deoxy-2^'-fluorocytidine, 2^'-O-methylcytidine and cytosine arabinoside are examined in the current work by measuring the infrared spectra in the IR fingerprint region using infrared multiple photon dissociation (IRMPD) action spectroscopy. The structures accessed in the experiments were determined via comparison of the measured IRMPD action spectra to the theoretical linear IR spectra determined by density functional theory and molecular modeling for the stable low-energy structures. Although glycosidic bond stability cannot be quantitatively determined from this data, complementary TCID studies will establish the effect of these modifications. Comparison of these modified nucleosides with their RNA and DNA analogues will help elucidate differences in their intrinsic chemistry.

The Histone Acetyltransferase MOF Promotes Induces Generation of Pluripotent Stem Cells.

PubMed

Mu, Xupeng; Yan, Shaohua; Fu, Changhao; Wei, Anhui

2015-08-01

Histone modification plays an important role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). The histone acetyltransferase MOF is a key regulator of ESCs; however, the role of MOF in the process of reprogramming back to induced pluripotent stem cells (iPSCs) remains unclear. In this study, we investigated the function of MOF on the generation of iPSCs. We show that iPSCs contain high levels of MOF mRNA, and the expression level of MOF protein is dramatically upregulated following reprogramming. Most importantly, overexpression of MOF improves reprogramming efficiency and facilitates the formation of iPSCs, whereas small hairpin RNA (shRNA)-mediated knockdown of MOF impairs iPSCs generation during reprogramming. Further investigation reveals that MOF interacts with the H3K4 methyltransferase Wdr5 to promote endogenous Oct4 expression during the reprogramming process. Knockdown of MOF reduces H4K16ac and H3K4me3 modification at the Oct4 promoter. In conclusion, our data indicate that MOF is an important epigenetic regulator that is critical for efficient reprogramming.

Peroxiredoxins: Guardians Against Oxidative Stress and Modulators of Peroxide Signaling

PubMed Central

Perkins, Arden; Nelson, Kimberly J.; Parsonage, Derek; Poole, Leslie B.; Karplus, P. Andrew

2015-01-01

Peroxiredoxins (Prxs) are a ubiquitous family of cysteine-dependent peroxidase enzymes that play dominant roles in regulating peroxide levels within cells. These enzymes, often present at high levels and capable of rapidly clearing peroxides, display a remarkable array of variations in their oligomeric states and susceptibility to regulation by hyperoxidative inactivation and other post-translational modifications. Key conserved residues within the active site promote catalysis by stabilizing the transition state required for transferring the terminal oxygen of hydroperoxides to the active site (peroxidatic) cysteine residue. Extensive investigations continue to expand our understanding of the scope of their importance as well as the structures and forces at play within these critical defense and regulatory enzymes. PMID:26067716

Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells

PubMed Central

Tsuchiya, Yugo; Peak-Chew, Sew Yeu; Newell, Clare; Miller-Aidoo, Sheritta; Mangal, Sriyash; Zhyvoloup, Alexander; Bakovic´, Jovana; Malanchuk, Oksana; Pereira, Gonçalo C.; Kotiadis, Vassilios; Szabadkai, Gyorgy; Duchen, Michael R.; Campbell, Mark; Cuenca, Sergio Rodriguez; Vidal-Puig, Antonio; James, Andrew M.; Murphy, Michael P.; Filonenko, Valeriy; Skehel, Mark

2017-01-01

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions. PMID:28341808

The cytosolic carboxypeptidases CCP2 and CCP3 catalyze posttranslational removal of acidic amino acids

PubMed Central

Tort, Olivia; Tanco, Sebastián; Rocha, Cecilia; Bièche, Ivan; Seixas, Cecilia; Bosc, Christophe; Andrieux, Annie; Moutin, Marie-Jo; Avilés, Francesc Xavier; Lorenzo, Julia; Janke, Carsten

2014-01-01

The posttranslational modification of carboxy-terminal tails of tubulin plays an important role in the regulation of the microtubule cytoskeleton. Enzymes responsible for deglutamylating tubulin have been discovered within a novel family of mammalian cytosolic carboxypeptidases. The discovery of these enzymes also revealed the existence of a range of other substrates that are enzymatically deglutamylated. Only four of six mammalian cytosolic carboxypeptidases had been enzymatically characterized. Here we complete the functional characterization of this protein family by demonstrating that CCP2 and CCP3 are deglutamylases, with CCP3 being able to hydrolyze aspartic acids with similar efficiency. Deaspartylation is a novel posttranslational modification that could, in conjunction with deglutamylation, broaden the range of potential substrates that undergo carboxy-terminal processing. In addition, we show that CCP2 and CCP3 are highly regulated proteins confined to ciliated tissues. The characterization of two novel enzymes for carboxy-terminal protein modification provides novel insights into the broadness of this barely studied process. PMID:25103237

Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin

PubMed Central

Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan; Krzyszton, Michal; Rothi, M Hafiz; Bouzit, Lilia; Wierzbicki, Andrzej T

2016-01-01

RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries. DOI: http://dx.doi.org/10.7554/eLife.19092.001 PMID:27779094

Cisplatin binds to pre-miR-200b and impairs its processing to mature microRNA.

PubMed

Mezencev, R; Wartell, R M

2018-01-01

Cisplatin is an important anticancer drug with a complex mode of action, a variety of possible targets, and numerous resistance mechanisms. While genomic DNA has traditionally been considered to be its most critical anticancer target, several lines of evidence suggest that various RNAs and other biomolecules may play a role in its anticancer mode of action. In this report we demonstrate that cisplatin modifies pre-miR-200b, impairs its processing to mature miRNA, and decreases miR-200b expression in ovarian cancer cells. Considering the role of miR-200b in epithelial-to-mesenchymal transition and cancer chemosensitivity, cisplatin-induced modification of pre-miR-200b and subsequent deregulation of mature miR-200b may, depending on cell context, limit anticancer activity of this important anticancer drug. More gener- ally, precursor miRNAs may be important targets of cisplatin and play a role in this drug's anticancer activity or modulate cell responses to this drug.

A Co-Precursor Approach Coupled with a Supercritical Modification Method for Constructing Highly Transparent and Superhydrophobic Polymethylsilsesquioxane Aerogels.

PubMed

Lei, Chaoshuai; Li, Junning; Sun, Chencheng; Yang, Hailong; Xia, Tao; Hu, Zijun; Zhang, Yue

2018-03-30

Polymethylsilsesquioxane (PMSQ) aerogels obtained from methyltrimethoxysilane (MTMS) are well-known high-performance porous materials. Highly transparent and hydrophobic PMSQ aerogel would play an important role in transparent vacuum insulation panels. Herein, the co-precursor approach and supercritical modification method were developed to prepare the PMSQ aerogels with high transparency and superhydrophobicity. Firstly, benefiting from the introduction of tetramethoxysilane (TMOS) in the precursor, the pore structure became more uniform and the particle size was decreased. As the TMOS content increased, the light transmittance increased gradually from 54.0% to 81.2%, whereas the contact angle of water droplet decreased from 141° to 99.9°, ascribed to the increase of hydroxyl groups on the skeleton surface. Hence, the supercritical modification method utilizing hexamethyldisilazane was also introduced to enhance the hydrophobic methyl groups on the aerogel's surface. As a result, the obtained aerogels revealed superhydrophobicity with a contact angle of 155°. Meanwhile, the developed surface modification method did not lead to any significant changes in the pore structure resulting in the superhydrophobic aerogel with a high transparency of 77.2%. The proposed co-precursor approach and supercritical modification method provide a new horizon in the fabrication of highly transparent and superhydrophobic PMSQ aerogels.

Specific cytoarchitectureal changes in hippocampal subareas in daDREAM mice.

PubMed

Mellström, Britt; Kastanauskaite, Asta; Knafo, Shira; Gonzalez, Paz; Dopazo, Xose M; Ruiz-Nuño, Ana; Jefferys, John G R; Zhuo, Min; Bliss, Tim V P; Naranjo, Jose R; DeFelipe, Javier

2016-02-29

Transcriptional repressor DREAM (downstream regulatory element antagonist modulator) is a Ca(2+)-binding protein that regulates Ca(2+) homeostasis through gene regulation and protein-protein interactions. It has been shown that a dominant active form (daDREAM) is implicated in learning-related synaptic plasticity such as LTP and LTD in the hippocampus. Neuronal spines are reported to play important roles in plasticity and memory. However, the possible role of DREAM in spine plasticity has not been reported. Here we show that potentiating DREAM activity, by overexpressing daDREAM, reduced dendritic basal arborization and spine density in CA1 pyramidal neurons and increased spine density in dendrites in dentate gyrus granule cells. These microanatomical changes are accompanied by significant modifications in the expression of specific genes encoding the cytoskeletal proteins Arc, Formin 1 and Gelsolin in daDREAM hippocampus. Our results strongly suggest that DREAM plays an important role in structural plasticity in the hippocampus.

Simultaneous Surface Modification and Chemical Reduction of Graphene Oxide Using Glucose.

PubMed

Pan, Hui; Liu, Ruiqi; Li, Guanglong; Wang, Xiaodong; Ding, Tao

2018-05-01

In this paper, we develop a simple and facile approach to prepare graphene nanosheets through chemical reduction with glucose as reducing agent and modification agent. The reduced and modified graphene by glucose (denoted as g-rGO) was characterized with techniques of Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Raman spectra, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), etc. It is found that, besides the desired reduction capability to graphene oxide (denoted as GO), glucose plays an important role as a modifying reagent in stabilizing the as-prepared graphene nanosheets simultaneously and the g-rGO exhibits good dispersibility and stability in water and waterborne polyurethane matrix (denoted as WPU). Moreover, the g-rGO can improve evidently the mechanical properties, weather ability and water resistance of WPU.

Manipulation of Metabolic Pathways to Develop Vitamin-Enriched Crops for Human Health

PubMed Central

Jiang, Ling; Wang, Weixuan; Lian, Tong; Zhang, Chunyi

2017-01-01

Vitamin deficiencies are major forms of micronutrient deficiencies, and are associated with huge economic losses as well as severe physical and intellectual damages to humans. Much evidence has demonstrated that biofortification plays an important role in combating vitamin deficiencies due to its economical and effective delivery of nutrients to populations in need. Biofortification enables food plants to be enriched with vitamins through conventional breeding and/or biotechnology. Here, we focus on the progress in the manipulation of the vitamin metabolism, an essential part of biofortification, by the genetic modification or by the marker-assisted selection to understand mechanisms underlying metabolic improvement in food plants. We also propose to integrate new breeding technologies with metabolic pathway modification to facilitate biofortification in food plants and, thereby, to benefit human health. PMID:28634484

Inland capture fishery contributions to global food security and threats to their future

USGS Publications Warehouse

Youn, So-Jung; Taylor, William W.; Lynch, Abigail J.; Cowx, Ian G.; Beard, T. Douglas; Bartley, Devin; Wu, Felicia

2014-01-01

Inland fish and fisheries play important roles in ensuring global food security. They provide a crucial source of animal protein and essential micronutrients for local communities, especially in the developing world. Data concerning fisheries production and consumption of freshwater fish are generally inadequately assessed, often leading decision makers to undervalue their importance. Modification of inland waterways for alternative uses of freshwater (particularly dams for hydropower and water diversions for human use) negatively impacts the productivity of inland fisheries for food security at local and regional levels. This paper highlights the importance of inland fisheries to global food security, the challenges they face due to competing demands for freshwater, and possible solutions.

Deglycosylation of glycoproteins with trifluoromethanesulphonic acid: elucidation of molecular structure and function.

PubMed Central

Edge, Albert S B

2003-01-01

The alteration of proteins by post-translational modifications, including phosphorylation, sulphation, processing by proteolysis, lipid attachment and glycosylation, gives rise to a broad range of molecules that can have an identical underlying protein core. An understanding of glycosylation of proteins is important in clarifying the nature of the numerous variants observed and in determining the biological roles of these modifications. Deglycosylation with TFMS (trifluoromethanesulphonic acid) [Edge, Faltynek, Hof, Reichert, and Weber, (1981) Anal. Biochem. 118, 131-137] has been used extensively to remove carbohydrate from glycoproteins, while leaving the protein backbone intact. Glycosylated proteins from animals, plants, fungi and bacteria have been deglycosylated with TFMS, and the most extensively studied types of carbohydrate chains in mammals, the N-linked, O-linked and glycosaminoglycan chains, are all removed by this procedure. The method is based on the finding that linkages between sugars are sensitive to cleavage by TFMS, whereas the peptide bond is stable and is not broken, even with prolonged deglycosylation. The relative susceptibility of individual sugars in glycosidic linkage varies with the substituents at C-2 and the occurrence of amido and acetyl groups, but even the most stable sugars are removed under conditions that are sufficiently mild to prevent scission of peptide bonds. The post-translational modifications of proteins have been shown to be required for diverse biological functions, and selective procedures to remove these modifications play an important role in the elucidation of protein structure and function. PMID:12974674

m6A RNA Methylation Controls Neural Development and Is Involved in Human Diseases.

PubMed

Du, Kunzhao; Zhang, Longbin; Lee, Trevor; Sun, Tao

2018-06-16

RNA modifications are involved in many aspects of biological functions. N6-methyladenosine (m 6 A) is one of the most important forms of RNA methylation and plays a vital role in regulating gene expression, protein translation, cell behaviors, and physiological conditions in many species, including humans. The dynamic and reversible modification of m 6 A is conducted by three elements: methyltransferases ("writers"), such as methyltransferase-like protein 3 (METTL3) and METTL14; m 6 A-binding proteins ("readers"), such as the YTH domain family proteins (YTHDFs) and YTH domain-containing protein 1 (YTHDC1); and demethylases ("erasers"), such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). In this review, we summarize the current knowledge on mapping mRNA positions of m 6 A modification and revealing molecular processes of m 6 A. We further highlight the biological significance of m 6 A modification in neural cells during development of the nervous system and its association with human diseases. m 6 A RNA methylation is becoming a new frontier in neuroscience and should help us better understand neural development and neurological diseases from a novel point of view.

The paternal hidden agenda: Epigenetic inheritance through sperm chromatin.

PubMed

Puri, Deepika; Dhawan, Jyotsna; Mishra, Rakesh K

2010-07-01

Epigenetic modifications play a crucial role in developmental gene regulation. These modifications, being reversible, provide a layer of information over and above the DNA sequence, that has plasticity and leads to the generation of cell type-specific epigenomes during cellular differentiation. In almost all higher eukaryotes, the oocyte provides not only its cytoplasm, mitochondria, maternally deposited RNA and proteins but also an epigenetic component in the form of DNA and histone-modifications. During spermeiogenesis however, most of the histones are replaced by protamines, leading to a loss of the epigenetic component. The sperm is, therefore, viewed as a passive carrier of the paternal genome with a disproportionate, lower epigenetic contribution except for DNA methylation, to the next generation. A recent study overturns this view by demonstrating a locus-specific retention of histones, with specific modifications in the sperm chromatin at the promoters of developmentally important genes. This programmed retention of epigenetic marks with a role in embryonic development is suggested to offset, in some measure, the dominant maternal effect. This new finding helps in addressing the question of epigenetic transmission of environmental and 'lifestyle' experiences across generations and raises the question of 'parental conflict' at the loci that may be differentially marked.

Phosphorylation of Elp1 by Hrr25 Is Required for Elongator-Dependent tRNA Modification in Yeast

PubMed Central

Abdel-Fattah, Wael; Jablonowski, Daniel; Di Santo, Rachael; Thüring, Kathrin L.; Scheidt, Viktor; Hammermeister, Alexander; ten Have, Sara; Helm, Mark; Schaffrath, Raffael; Stark, Michael J. R.

2015-01-01

Elongator is a conserved protein complex comprising six different polypeptides that has been ascribed a wide range of functions, but which is now known to be required for modification of uridine residues in the wobble position of a subset of tRNAs in yeast, plants, worms and mammals. In previous work, we showed that Elongator's largest subunit (Elp1; also known as Iki3) was phosphorylated and implicated the yeast casein kinase I Hrr25 in Elongator function. Here we report identification of nine in vivo phosphorylation sites within Elp1 and show that four of these, clustered close to the Elp1 C-terminus and adjacent to a region that binds tRNA, are important for Elongator's tRNA modification function. Hrr25 protein kinase directly modifies Elp1 on two sites (Ser-1198 and Ser-1202) and through analyzing non-phosphorylatable (alanine) and acidic, phosphomimic substitutions at Ser-1198, Ser-1202 and Ser-1209, we provide evidence that phosphorylation plays a positive role in the tRNA modification function of Elongator and may regulate the interaction of Elongator both with its accessory protein Kti12 and with Hrr25 kinase. PMID:25569479

Genome-wide analyses of four major histone modifications in Arabidopsis hybrids at the germinating seed stage.

PubMed

Zhu, Anyu; Greaves, Ian K; Dennis, Elizabeth S; Peacock, W James

2017-02-07

Hybrid vigour (heterosis) has been used for decades in cropping agriculture, especially in the production of maize and rice, because hybrid varieties exceed their parents in plant biomass and seed yield. The molecular basis of hybrid vigour is not fully understood. Previous studies have suggested that epigenetic systems could play a role in heterosis. In this project, we investigated genome-wide patterns of four histone modifications in Arabidopsis hybrids in germinating seeds. We found that although hybrids have similar histone modification patterns to the parents in most regions of the genome, they have altered patterns at specific loci. A small subset of genes show changes in histone modifications in the hybrids that correlate with changes in gene expression. Our results also show that genome-wide patterns of histone modifications in geminating seeds parallel those at later developmental stages of seedlings. Ler/C24 hybrids showed similar genome-wide patterns of histone modifications as the parents at an early germination stage. However, a small subset of genes, such as FLC, showed correlated changes in histone modification and in gene expression in the hybrids. The altered patterns of histone modifications for those genes in hybrids could be related to some heterotic traits in Arabidopsis, such as flowering time, and could play a role in hybrid vigour establishment.

Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

PubMed

Johnson, Nicole L; Carini, Lindsay; Schenk, Marian E; Stewart, Michelle; Byrnes, Elizabeth M

2011-01-01

The non-medical use of prescription opiates, such as Vicodin(®) and MSContin(®), has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females' spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

Roles of O-GlcNAc in chronic diseases of aging.

PubMed

Banerjee, Partha S; Lagerlöf, Olof; Hart, Gerald W

2016-10-01

O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive-behavioral play therapy.

PubMed

Knell, S M

1998-03-01

Discusses cognitive-behavioral play therapy (CBPT), a developmentally sensitive treatment for young children that relies on flexibility, decreased expectation for verbalizations by the child, and increased reliance on experiential approaches. The development of CBPT for preschool-age children provides a relatively unique adaptation of cognitive therapy as it was originally developed for adults. CBPT typically contains a modeling component through which adaptive coping skills are demonstrated. Through the use of play, cognitive change is communicated indirectly, and more adaptive behaviors can be introduced to the child. Modeling is tailored for use with many specific cognitive and behavioral interventions. Generalization and response prevention are important features of CBPT. With minor modifications, many of the principles of cognitive therapy, as delineated for use with adults, are applicable to young children. Case examples are presented to highlight the application of CBPT. Although CBPT has a sound therapeutic base and utilizes proven techniques, more rigorous empirical scrutiny is needed.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

PubMed

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-09-03

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism

PubMed Central

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-01-01

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression. PMID:27598153

Post-translational modifications of linker histone H1 variants in mammals

NASA Astrophysics Data System (ADS)

Starkova, T. Yu; Polyanichko, A. M.; Artamonova, T. O.; Khodorkovskii, M. A.; Kostyleva, E. I.; Chikhirzhina, E. V.; Tomilin, A. N.

2017-02-01

The covalent modifications of the linker histone H1 and the core histones are thought to play an important role in the control of chromatin functioning. Histone H1 variants from K562 cell line (hH1), mouse (mH1) and calf (cH1) thymi were studied by matrix-activated laser desorption/ionization fourier transform ion cyclotron resonance mass-spectroscopy (MALDI-FT-ICR-MS). The proteomics analysis revealed novel post-translational modifications of the histone H1, such as meK34-mH1.4, meK35-cH1.1, meK35-mH1.1, meK75-hH1.2, meK75-hH1.3, acK26-hH1.4, acK26-hH1.3 and acK17-hH1.1. The comparison of the hH1, mH1 and cH1 proteins has demonstrated that the types and positions of the post-translational modifications of the globular domains of the H1.2-H1.4 variants are very conservative. However, the post-translational modifications of the N- and C-terminal tails of H1.2, H1.3 and H1.4 are different. The differences of post-translational modifications in the N- and C-terminal tails of H1.2, H1.3 and H1.4 likely lead to the differences in DNA-H1 and H1-protein interactions.

Golf in the United States: an evolution of accessibility.

PubMed

Parziale, John R

2014-09-01

Golf affords physical and psychological benefits to persons who are physically challenged. Advances in adaptive technology, changes in golf course design, and rules modifications have enabled persons with neurological, musculoskeletal, and other impairments to play golf at a recreational, elite amateur, or professional level. The Americans with Disabilities Act has been cited in both federal and US Supreme Court rulings that have improved access for physically challenged golfers. Medical specialties, including physiatry, have played an important role in this process. This article reviews the history of golf's improvements in accessibility, and provides clinicians and physically challenged golfers with information that will facilitate participation in the sport. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

The role of play objects and object play in human cognitive evolution and innovation

PubMed Central

Johannsen, Niels N.; Högberg, Anders; Nowell, April; Lombard, Marlize

2018-01-01

Abstract In this contribution, we address a major puzzle in the evolution of human material culture: If maturing individuals just learn their parental generation's material culture, then what is the origin of key innovations as documented in the archeological record? We approach this question by coupling a life‐history model of the costs and benefits of experimentation with a niche‐construction perspective. Niche‐construction theory suggests that the behavior of organisms and their modification of the world around them have important evolutionary ramifications by altering developmental settings and selection pressures. Part of Homo sapiens' niche is the active provisioning of children with play objects — sometimes functional miniatures of adult tools — and the encouragement of object play, such as playful knapping with stones. Our model suggests that salient material culture innovation may occur or be primed in a late childhood or adolescence sweet spot when cognitive and physical abilities are sufficiently mature but before the full onset of the concerns and costs associated with reproduction. We evaluate the model against a series of archeological cases and make suggestions for future research. PMID:29446561

Targeting the Regulatory Machinery of BIM for Cancer Therapy

PubMed Central

Harada, Hisashi; Grant, Steven

2013-01-01

BIM represents a BH3-only proapoptotic member of the BCL-2 family of apoptotic regulatory proteins. Recent evidence suggests that in addition to its involvement in normal homeostasis, BIM plays a critical role in tumor cell biology, including the regulation of tumorigenesis through activities as a tumor suppressor, tumor metastasis, and tumor cell survival. Consequently, BIM has become the focus of intense interest as a potential target for cancer chemotherapy. The control of BIM expression is complex, and involves multiple factors, including epigenetic events (i.e., promoter acetylation or methylation, miRNA), transcription factors, posttranscriptional regulation, and posttranslational modifications, most notably phosphorylation. Significantly, the expression of BIM by tumor cells has been shown to play an important role in determining the response of transformed cells to not only conventional cytotoxic agents, but also to a broad array of targeted agents that interrupt cell signaling and survival pathways. Furthermore, modifications in BIM expression may be exploited to improve the therapeutic activity and potentially the selectivity of such agents. It is likely that evolving insights into the factors that regulate BIM expression will ultimately lead to novel BIM-based therapeutic strategies in the future. PMID:22856430

Functional importance of Ψ38 and Ψ39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast

PubMed Central

Han, Lu; Kon, Yoshiko

2015-01-01

The numerous modifications of tRNA play central roles in controlling tRNA structure and translation. Modifications in and around the anticodon loop often have critical roles in decoding mRNA and in maintaining its reading frame. Residues U38 and U39 in the anticodon stem–loop are frequently modified to pseudouridine (Ψ) by members of the widely conserved TruA/Pus3 family of pseudouridylases. We investigate here the cause of the temperature sensitivity of pus3Δ mutants of the yeast Saccharomyces cerevisiae and find that, although Ψ38 or Ψ39 is found on at least 19 characterized cytoplasmic tRNA species, the temperature sensitivity is primarily due to poor function of tRNAGln(UUG), which normally has Ψ38. Further investigation reveals that at elevated temperatures there are substantially reduced levels of the s2U moiety of mcm5s2U34 of tRNAGln(UUG) and the other two cytoplasmic species with mcm5s2U34, that the reduced s2U levels occur in the parent strain BY4741 and in the widely used strain W303, and that reduced levels of the s2U moiety are detectable in BY4741 at temperatures as low as 33°C. Additional examination of the role of Ψ38,39 provides evidence that Ψ38 is important for function of tRNAGln(UUG) at permissive temperature, and indicates that Ψ39 is important for the function of tRNATrp(CCA) in trm10Δ pus3Δ mutants and of tRNALeu(CAA) as a UAG nonsense suppressor. These results provide evidence for important roles of both Ψ38 and Ψ39 in specific tRNAs, and establish that modification of the wobble position is subject to change under relatively mild growth conditions. PMID:25505024

A Genetically Encoded Probe for Live-Cell Imaging of H4K20 Monomethylation.

PubMed

Sato, Yuko; Kujirai, Tomoya; Arai, Ritsuko; Asakawa, Haruhiko; Ohtsuki, Chizuru; Horikoshi, Naoki; Yamagata, Kazuo; Ueda, Jun; Nagase, Takahiro; Haraguchi, Tokuko; Hiraoka, Yasushi; Kimura, Akatsuki; Kurumizaka, Hitoshi; Kimura, Hiroshi

2016-10-09

Eukaryotic gene expression is regulated in the context of chromatin. Dynamic changes in post-translational histone modification are thought to play key roles in fundamental cellular functions such as regulation of the cell cycle, development, and differentiation. To elucidate the relationship between histone modifications and cellular functions, it is important to monitor the dynamics of modifications in single living cells. A genetically encoded probe called mintbody (modification-specific intracellular antibody), which is a single-chain variable fragment tagged with a fluorescent protein, has been proposed as a useful visualization tool. However, the efficacy of intracellular expression of antibody fragments has been limited, in part due to different environmental conditions in the cytoplasm compared to the endoplasmic reticulum where secreted proteins such as antibodies are folded. In this study, we have developed a new mintbody specific for histone H4 Lys20 monomethylation (H4K20me1). The specificity of the H4K20me1-mintbody in living cells was verified using yeast mutants and mammalian cells in which this target modification was diminished. Expression of the H4K20me1-mintbody allowed us to monitor the oscillation of H4K20me1 levels during the cell cycle. Moreover, dosage-compensated X chromosomes were visualized using the H4K20me1-mintbody in mouse and nematode cells. Using X-ray crystallography and mutational analyses, we identified critical amino acids that contributed to stabilization and/or proper folding of the mintbody. Taken together, these data provide important implications for future studies aimed at developing functional intracellular antibodies. Specifically, the H4K20me1-mintbody provides a powerful tool to track this particular histone modification in living cells and organisms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells

PubMed Central

Watanabe, Yukiko; Onodera, Atsushi; Kanai, Urara; Ichikawa, Tomomi; Obata-Ninomiya, Kazushige; Wada, Tomoko; Kiuchi, Masahiro; Iwamura, Chiaki; Tumes, Damon J.; Shinoda, Kenta; Yagi, Ryoji; Motohashi, Shinichiro; Hirahara, Kiyoshi; Nakayama, Toshinori

2014-01-01

Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin−/− T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression. PMID:25136117

Recording electrocardiograms using 3-limb lead cables instead of the standard 4: a modification to minimize incorrect electrode placements.

PubMed

Soliman, Elsayed Z

2008-01-01

The similarity between and the number of limb lead cables play an important role in the frequency of incorrect connection of limb electrodes. Hence, a modified electrocardiogram (ECG) acquisition procedure is proposed in this brief communication, whereby the left-leg (LL) and right-leg (RL) electrode cables are combined into 1 cable, referred to as combined LL/RL cable. The electrode wires in the combined LL/RL cable are connected to 2 electrodes placed on both sides of the LL. The combined LL/RL cable is unique enough (being thicker) not to be mistaken with the upper limb electrode cables. The proposed modification will not in any way influence the ECG waveforms or amplitudes, and it can be expected to substantially reduce incorrect limb electrode placements.

Lightness modification of color image for protanopia and deuteranopia

NASA Astrophysics Data System (ADS)

Tanaka, Go; Suetake, Noriaki; Uchino, Eiji

2010-01-01

In multimedia content, colors play important roles in conveying visual information. However, color information cannot always be perceived uniformly by all people. People with a color vision deficiency, such as dichromacy, cannot recognize and distinguish certain color combinations. In this paper, an effective lightness modification method, which enables barrier-free color vision for people with dichromacy, especially protanopia or deuteranopia, while preserving the color information in the original image for people with standard color vision, is proposed. In the proposed method, an optimization problem concerning lightness components is first defined by considering color differences in an input image. Then a perceptible and comprehensible color image for both protanopes and viewers with no color vision deficiency or both deuteranopes and viewers with no color vision deficiency is obtained by solving the optimization problem. Through experiments, the effectiveness of the proposed method is illustrated.

Role of the plant cell wall in gravity resistance.

PubMed

Hoson, Takayuki; Wakabayashi, Kazuyuki

2015-04-01

Gravity resistance, mechanical resistance to the gravitational force, is a principal graviresponse in plants, comparable to gravitropism. The cell wall is responsible for the final step of gravity resistance. The gravity signal increases the rigidity of the cell wall via the accumulation of its constituents, polymerization of certain matrix polysaccharides due to the suppression of breakdown, stimulation of cross-link formation, and modifications to the wall environment, in a wide range of situations from microgravity in space to hypergravity. Plants thus develop a tough body to resist the gravitational force via an increase in cell wall rigidity and the modification of growth anisotropy. The development of gravity resistance mechanisms has played an important role in the acquisition of responses to various mechanical stresses and the evolution of land plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plant hormone signaling in flowering: An epigenetic point of view.

PubMed

Campos-Rivero, Gerardo; Osorio-Montalvo, Pedro; Sánchez-Borges, Rafael; Us-Camas, Rosa; Duarte-Aké, Fátima; De-la-Peña, Clelia

2017-07-01

Reproduction is one of the most important phases in an organism's lifecycle. In the case of angiosperm plants, flowering provides the major developmental transition from the vegetative to the reproductive stage, and requires genetic and epigenetic reprogramming to ensure the success of seed production. Flowering is regulated by a complex network of genes that integrate multiple environmental cues and endogenous signals so that flowering occurs at the right time; hormone regulation, signaling and homeostasis are very important in this process. Working alone or in combination, hormones are able to promote flowering by epigenetic regulation. Some plant hormones, such as gibberellins, jasmonic acid, abscisic acid and auxins, have important effects on chromatin compaction mediated by DNA methylation and histone posttranslational modifications, which hints at the role that epigenetic regulation may play in flowering through hormone action. miRNAs have been viewed as acting independently from DNA methylation and histone modification, ignoring their potential to interact with hormone signaling - including the signaling of auxins, gibberellins, ethylene, jasmonic acid, salicylic acid and others - to regulate flowering. Therefore, in this review we examine new findings about interactions between epigenetic mechanisms and key players in hormone signaling to coordinate flowering. Copyright © 2017 Elsevier GmbH. All rights reserved.

Molecular docking and ADME-toxicity studies of potential compounds of medicinal plants grown in Indonesia as an anti-rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Awaluddin, Rizki; Muhtadi, Wildan Khairi; Chabib, Lutfi; Ikawati, Zullies; Martien, Ronny; Ismail, Hilda

2017-03-01

Rheumatoid arthritis (RA) is an autoimmune disease with recurrent bone destruction around the joints that could lead to permanent joint damage. DMARDs (Disease Modifying Anti-Rheumatoid Drugs) and NSAIDs (Non-Steroid Anti-Inflammatory Drugs) are the RA therapies with many side effects on long term use. Based on the ethnomedicine, there are many plants that could be found in Indonesia that contain the potential compounds as alternative RA therapies. The aim of this study is to assess the potential of compounds of various medicinal plants against multiple proteins that play an important role on RA through the molecular docking study and pharmacokinetic prediction. Hesperidin, EGCG (Epigallocatechin gallate), and mangiferin showed higher activity compared to the other compounds against TACE (TNF-α converting enzyme) which play an important role in the inhibition of TNF-α. Inhibition on it could suppress macrophage cell and T-cell activity by suppressing the regulation of cytokine secretion against inflammation. Furthermore, hesperidin, EGCG, and mangiferin did not show effects on CYP450 (cytochrome P450). Modification of drug delivery system must be done to increase the bioavailability of the compounds. It can be concluded that hesperidin, EGCG, and mangiferin are potential to be developed as an RA therapy with a modification of drug delivery system. This study suggest the encapsulation method using liposome as the drug carrier, which is suitable with the charactheristic of hesperidine, EGCG, and mangiferin.

Glycosyltransferase-mediated Sweet Modification in Oral Streptococci.

PubMed

Zhu, F; Zhang, H; Wu, H

2015-05-01

Bacterial glycosyltransferases play important roles in bacterial fitness and virulence. Oral streptococci have evolved diverse strategies to survive and thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2 important biological processes mediated by 2 distinct groups of glycosyltransferases in oral streptococci that are important for bacterial colonization and virulence. The first process is the glycosylation of highly conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using Streptococcus parasanguinis as a model, we highlight new features of several glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1. Distinct features of a novel glycosyltransferase fold from a domain of unknown function 1792 are contrasted with common properties of canonical glycosyltransferases. The second biological process we cover is involved in building sticky glucan matrix to establish cariogenic biofilms by an important opportunistic pathogen Streptococcus mutans through the action of a family of 3 glucosyltransferases. We focus on discussing the structural feature of this family as a glycoside hydrolase family of enzymes. While the 2 processes are distinct, they all produce carbohydrate-coated biomolecules, which enable bacteria to stick better in the complex oral microbiome. Understanding the making of the sweet modification presents a unique opportunity to develop novel antiadhesion and antibiofilm strategies to fight infections by oral streptococci and beyond. © International & American Associations for Dental Research 2015.

Glycosyltransferase-mediated Sweet Modification in Oral Streptococci

PubMed Central

Zhu, F.; Zhang, H.

2015-01-01

Bacterial glycosyltransferases play important roles in bacterial fitness and virulence. Oral streptococci have evolved diverse strategies to survive and thrive in the carbohydrate-rich oral cavity. In this review, we discuss 2 important biological processes mediated by 2 distinct groups of glycosyltransferases in oral streptococci that are important for bacterial colonization and virulence. The first process is the glycosylation of highly conserved serine-rich repeat adhesins by a series of glycosyltransferases. Using Streptococcus parasanguinis as a model, we highlight new features of several glycosyltransferases that sequentially modify the serine-rich glycoprotein Fap1. Distinct features of a novel glycosyltransferase fold from a domain of unknown function 1792 are contrasted with common properties of canonical glycosyltransferases. The second biological process we cover is involved in building sticky glucan matrix to establish cariogenic biofilms by an important opportunistic pathogen Streptococcus mutans through the action of a family of 3 glucosyltransferases. We focus on discussing the structural feature of this family as a glycoside hydrolase family of enzymes. While the 2 processes are distinct, they all produce carbohydrate-coated biomolecules, which enable bacteria to stick better in the complex oral microbiome. Understanding the making of the sweet modification presents a unique opportunity to develop novel antiadhesion and antibiofilm strategies to fight infections by oral streptococci and beyond. PMID:25755271

m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

PubMed Central

Cui, Qi; Shi, Hailing; Ye, Peng; Li, Li; Qu, Qiuhao; Sun, Guoqiang; Sun, Guihua; Lu, Zhike; Huang, Yue; Yang, Cai-Guang; Riggs, Arthur D.

2017-01-01

Summary RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma. PMID:28297667

Post-translational modification of therapeutic peptides by NisB, the dehydratase of the lantibiotic nisin.

PubMed

Kluskens, Leon D; Kuipers, Anneke; Rink, Rick; de Boef, Esther; Fekken, Susan; Driessen, Arnold J M; Kuipers, Oscar P; Moll, Gert N

2005-09-27

Post-translationally introduced dehydroamino acids often play an important role in the activity and receptor specificity of biologically active peptides. In addition, a dehydroamino acid can be coupled to a cysteine to yield a cyclized peptide with increased biostability and resistance against proteolytic degradation and/or modified specificity. The lantibiotic nisin is an antimicrobial peptide produced by Lactococcus lactis. Its post-translational enzymatic modification involves NisB-mediated dehydration of serines and threonines and NisC-catalyzed coupling of cysteines to dehydroresidues, followed by NisT-mediated secretion. Here, we demonstrate that a L. lactis strain containing the nisBTC genes effectively dehydrates and secretes a wide range of medically relevant nonlantibiotic peptides among which variants of adrenocorticotropic hormone, vasopressin, an inhibitor of tripeptidyl peptidase II, enkephalin, luteinizing hormone-releasing hormone, angiotensin, and erythropoietin. For most of these peptides, ring formation was demonstrated. These data show that lantibiotic enzymes can be applied for the modification of peptides, thereby enabling the biotechnological production of dehydroresidue-containing and/or thioether-bridged therapeutic peptides with enhanced stability and/or modulated activities.

Interaction Network and Localization of Brucella abortus Membrane Proteins Involved in the Synthesis, Transport, and Succinylation of Cyclic β-1,2-Glucans

PubMed Central

Guidolin, Leticia S.; Morrone Seijo, Susana M.; Guaimas, Francisco F.

2015-01-01

ABSTRACT Cyclic β-1,2-glucans (CβG) are periplasmic homopolysaccharides that play an important role in the virulence and interaction of Brucella with the host. Once synthesized in the cytoplasm by the CβG synthase (Cgs), CβG are transported to the periplasm by the CβG transporter (Cgt) and succinylated by the CβG modifier enzyme (Cgm). Here, we used a bacterial two-hybrid system and coimmunoprecipitation techniques to study the interaction network between these three integral inner membrane proteins. Our results indicate that Cgs, Cgt, and Cgm can form both homotypic and heterotypic interactions. Analyses carried out with Cgs mutants revealed that the N-terminal region of the protein (Cgs region 1 to 418) is required to sustain the interactions with Cgt and Cgm as well as with itself. We demonstrated by single-cell fluorescence analysis that in Brucella, Cgs and Cgt are focally distributed in the membrane, particularly at the cell poles, whereas Cgm is mostly distributed throughout the membrane with a slight accumulation at the poles colocalizing with the other partners. In summary, our results demonstrate that Cgs, Cgt, and Cgm form a membrane-associated biosynthetic complex. We propose that the formation of a membrane complex could serve as a mechanism to ensure the fidelity of CβG biosynthesis by coordinating their synthesis with the transport and modification. IMPORTANCE In this study, we analyzed the interaction and localization of the proteins involved in the synthesis, transport, and modification of Brucella abortus cyclic β-1,2-glucans (CβG), which play an important role in the virulence and interaction of Brucella with the host. We demonstrate that these proteins interact, forming a complex located mainly at the cell poles; this is the first experimental evidence of the existence of a multienzymatic complex involved in the metabolism of osmoregulated periplasmic glucans in bacteria and argues for another example of pole differentiation in Brucella. We propose that the formation of this membrane complex could serve as a mechanism to ensure the fidelity of CβG biosynthesis by coordinating synthesis with the transport and modification. PMID:25733613

Importance of surface modification of γ-alumina in creating its nanostructured composites with zeolitic imidazolate framework ZIF-67.

PubMed

Liu, Yuanyuan; Gonçalves, Alexandre A S; Zhou, Yang; Jaroniec, Mietek

2018-05-07

Application of zeolitic imidazolate framework-67 (ZIF-67) as an adsorbent has been greatly hindered by slow mass transfer of adsorbate molecules due to its inherent microporosity. To address this limitation, we have developed binary nanostructures composed of ZIF-67 and γ-alumina (GA) containing respectively micropores and large mesopores. The nanostructured composites were successfully prepared by coupling ZIF-67 and GA with and without surface modification with imidazole silane that mimics the building blocks of ZIF-67 to obtain GA-Im-ZIF-67 (with imidazole silane) and GA-ZIF-67 (without imidazole silane). The sizes of ZIF-67 crystals in these composites were smaller as compared to those of pure ZIF-67, and the textural properties of these composites with and without surface modification were quite similar. However, the surface grafting of alumina with imidazole silane played an important role in improving interfacial coupling between GA and ZIF-67, which resulted in significant changes in the dispersion of ZIF-67 crystals and better adsorption properties. The presence of large mesopores in the alumina-based composites containing smaller ZIF-67 crystals improved their adsorption properties toward dyes such as Rhodamine B (RhB). The RhB adsorption capacity of GA-Im-ZIF-67 was much higher than that of GA-ZIF-67, suggesting that the imidazole silane modification of GA before its coupling with ZIF-67 and the GA mesoporosity were essential for a substantial increase in the adsorption capacity of RhB. Copyright © 2018 Elsevier Inc. All rights reserved.

Modifications of Glycans: Biological Significance and Therapeutic Opportunities

PubMed Central

Muthana, Saddam M.; Campbell, Christopher; Gildersleeve, Jeffrey C.

2012-01-01

Carbohydrates play a central role in a wide range of biological processes. As with nucleic acids and proteins, modifications of specific sites within the glycan chain can modulate a carbohydrate’s overall biological function. For example, acylation, methylation, sulfation, epimerization, and phosphorylation can occur at various positions within a carbohydrate to modulate bioactivity. Therefore, there is significant interest in identifying discrete carbohydrate modifications and understanding their biological effects. Additionally, enzymes that catalyze those modifications and proteins that bind modified glycans provide numerous targets for therapeutic intervention. This review will focus on modifications of glycans that occur after the oligomer/polymer has been assembled, generally referred to as postglycosylational modifications. PMID:22195988

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

PubMed Central

Mason, Mike J; Fan, Guoping; Plath, Kathrin; Zhou, Qing; Horvath, Steve

2009-01-01

Background Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes. Results We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation. Conclusion Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology. PMID:19619308

Phosphorylation of glutaminase by PKCε is essential for its enzymatic activity and critically contributes to tumorigenesis.

PubMed

Han, Tianyu; Zhan, Weihua; Gan, Mingxi; Liu, Fanrong; Yu, Bentong; Chin, Y Eugene; Wang, Jian-Bin

2018-06-01

Glutamine metabolism plays an important role in cancer development and progression. Glutaminase C (GAC), the first enzyme in glutaminolysis, has emerged as an important target for cancer therapy and many studies have focused on the mechanism of enhanced GAC expression in cancer cells. However, little is known about the post-translational modification of GAC. Here, we report that phosphorylation is a crucial post-translational modification of GAC, which is responsible for the higher glutaminase activity in lung tumor tissues and cancer cells. We identify the key Ser314 phosphorylation site on GAC that is regulated by the NF-κB-PKCε axis. Blocking Ser314 phosphorylation by the S314A mutation in lung cancer cells inhibits the glutaminase activity, triggers genetic reprogramming, and alleviates tumor malignancy. Furthermore, we find that a high level of GAC phosphorylation correlates with poor survival rate of lung cancer patients. These findings highlight a previously unappreciated mechanism for activation of GAC by phosphorylation and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.

Oligophrenin-1 (OPHN1), a Gene Involved in X-Linked Intellectual Disability, Undergoes RNA Editing and Alternative Splicing during Human Brain Development

PubMed Central

Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development. PMID:24637888

Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development.

PubMed

Barresi, Sabina; Tomaselli, Sara; Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development.

A homology-based pipeline for global prediction of post-translational modification sites

NASA Astrophysics Data System (ADS)

Chen, Xiang; Shi, Shao-Ping; Xu, Hao-Dong; Suo, Sheng-Bao; Qiu, Jian-Ding

2016-05-01

The pathways of protein post-translational modifications (PTMs) have been shown to play particularly important roles for almost any biological process. Identification of PTM substrates along with information on the exact sites is fundamental for fully understanding or controlling biological processes. Alternative computational strategies would help to annotate PTMs in a high-throughput manner. Traditional algorithms are suited for identifying the common organisms and tissues that have a complete PTM atlas or extensive experimental data. While annotation of rare PTMs in most organisms is a clear challenge. In this work, to this end we have developed a novel homology-based pipeline named PTMProber that allows identification of potential modification sites for most of the proteomes lacking PTMs data. Cross-promotion E-value (CPE) as stringent benchmark has been used in our pipeline to evaluate homology to known modification sites. Independent-validation tests show that PTMProber achieves over 58.8% recall with high precision by CPE benchmark. Comparisons with other machine-learning tools show that PTMProber pipeline performs better on general predictions. In addition, we developed a web-based tool to integrate this pipeline at http://bioinfo.ncu.edu.cn/PTMProber/index.aspx. In addition to pre-constructed prediction models of PTM, the website provides an extensional functionality to allow users to customize models.

Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations.

PubMed

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S; SantaLucia, John

2014-04-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson-Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity.

Oxidative Modulation of Voltage-Gated Potassium Channels

PubMed Central

Sahoo, Nirakar; Hoshi, Toshinori

2014-01-01

Abstract Significance: Voltage-gated K+ channels are a large family of K+-selective ion channel protein complexes that open on membrane depolarization. These K+ channels are expressed in diverse tissues and their function is vital for numerous physiological processes, in particular of neurons and muscle cells. Potentially reversible oxidative regulation of voltage-gated K+ channels by reactive species such as reactive oxygen species (ROS) represents a contributing mechanism of normal cellular plasticity and may play important roles in diverse pathologies including neurodegenerative diseases. Recent Advances: Studies using various protocols of oxidative modification, site-directed mutagenesis, and structural and kinetic modeling provide a broader phenomenology and emerging mechanistic insights. Critical Issues: Physicochemical mechanisms of the functional consequences of oxidative modifications of voltage-gated K+ channels are only beginning to be revealed. In vivo documentation of oxidative modifications of specific amino-acid residues of various voltage-gated K+ channel proteins, including the target specificity issue, is largely absent. Future Directions: High-resolution chemical and proteomic analysis of ion channel proteins with respect to oxidative modification combined with ongoing studies on channel structure and function will provide a better understanding of how the function of voltage-gated K+ channels is tuned by ROS and the corresponding reducing enzymes to meet cellular needs. Antioxid. Redox Signal. 21, 933–952. PMID:24040918

Ray craters on Ganymede: Implications for cratering apex-antapex asymmetry and surface modification processes

NASA Astrophysics Data System (ADS)

Xu, Luyuan; Hirata, Naoyuki; Miyamoto, Hideaki

2017-10-01

As the youngest features on Ganymede, ray craters are useful in revealing the sources of recent impactors and surface modification processes on the satellite. We examine craters with D > 10 km on Ganymede from images obtained by the Voyager and Galileo spacecraft to identify ray craters and study their spatial distributions. Furthermore, we carefully select images of appropriate solar and emission angles to obtain unbiased ray crater densities. As a result, we find that the density of large ray craters (D > 25 km) on the bright terrain exhibits an apex-antapex asymmetry, and its degree of asymmetry is much lower than the theoretical estimation for ecliptic comets. For large craters (D > 25 km), ecliptic comets ought to be less important than previously assumed, and a possible explanation is that nearly isotropic comets may play a more important role on Ganymede than previously thought. We also find that small ray craters (10 km < D < 25 km) on the bright terrain and ray craters (D > 10 km) on the dark terrain show no apex-antapex asymmetry. We interpret that the distribution difference between the terrain types comes from preferential thermal sublimation on the dark terrain, while the distribution difference between large and small ray craters suggests that rays of small craters are more readily erased by some surface modification processes, such as micrometeorite gardening.

Simulating smokers' acceptance of modifications in a cessation program.

PubMed Central

Spoth, R

1992-01-01

Recent research has underscored the importance of assessing barriers to smokers' acceptance of cessation programs. This paper illustrates the use of computer simulations to gauge smokers' response to program modifications which may produce barriers to participation. It also highlights methodological issues encountered in conducting this work. Computer simulations were based on conjoint analysis, a consumer research method which enables measurement of smokers' relative preference for various modifications of cessation programs. Results from two studies are presented in this paper. The primary study used a randomly selected sample of 218 adult smokers who participated in a computer-assisted phone interview. Initially, the study assessed smokers' relative utility rating of 30 features of cessation programs. Utility data were used in computer-simulated comparisons of a low-cost, self-help oriented program under development and five other existing programs. A baseline version of the program under development and two modifications (for example, use of a support group with a higher level of cost) were simulated. Both the baseline version and modifications received a favorable response vis-à-vis comparison programs. Modifications requiring higher program costs were, however, associated with moderately reduced levels of favorable consumer response. The second study used a sample of 70 smokers who responded to an expanded set of smoking cessation program features focusing on program packaging. This secondary study incorporate in-person, computer-assisted interviews at a shopping mall, with smokers viewing an artist's mock-up of various program options on display. A similar pattern of responses to simulated program modifications emerged, with monetary cost apparently playing a key role. The significance of conjoint-based computer simulation as a tool in program development or dissemination, salient methodological issues, and implications for further research are discussed. PMID:1738813

Simulating smokers' acceptance of modifications in a cessation program.

PubMed

Spoth, R

1992-01-01

Recent research has underscored the importance of assessing barriers to smokers' acceptance of cessation programs. This paper illustrates the use of computer simulations to gauge smokers' response to program modifications which may produce barriers to participation. It also highlights methodological issues encountered in conducting this work. Computer simulations were based on conjoint analysis, a consumer research method which enables measurement of smokers' relative preference for various modifications of cessation programs. Results from two studies are presented in this paper. The primary study used a randomly selected sample of 218 adult smokers who participated in a computer-assisted phone interview. Initially, the study assessed smokers' relative utility rating of 30 features of cessation programs. Utility data were used in computer-simulated comparisons of a low-cost, self-help oriented program under development and five other existing programs. A baseline version of the program under development and two modifications (for example, use of a support group with a higher level of cost) were simulated. Both the baseline version and modifications received a favorable response vis-à-vis comparison programs. Modifications requiring higher program costs were, however, associated with moderately reduced levels of favorable consumer response. The second study used a sample of 70 smokers who responded to an expanded set of smoking cessation program features focusing on program packaging. This secondary study incorporate in-person, computer-assisted interviews at a shopping mall, with smokers viewing an artist's mock-up of various program options on display. A similar pattern of responses to simulated program modifications emerged, with monetary cost apparently playing a key role. The significance of conjoint-based computer simulation as a tool in program development or dissemination, salient methodological issues, and implications for further research are discussed.

Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation

PubMed Central

Celi, Pietro; Gabai, Gianfranco

2015-01-01

This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions, such as respiratory diseases and parasitic infection; however, some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions, such as reproduction, nutrition, metabolism, lactation, gut health, and neonatal physiology. As the characterization of the mechanisms by which OS may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins. PMID:26664975

The human gut microbiota and its interactive connections to diet.

PubMed

Milani, C; Ferrario, C; Turroni, F; Duranti, S; Mangifesta, M; van Sinderen, D; Ventura, M

2016-10-01

The microbiota of the gastrointestinal tract plays an important role in human health. In addition to their metabolic interactions with dietary constituents, gut bacteria may also be involved in more complex host interactions, such as modulation of the immune system. Furthermore, the composition of the gut microbiota may be important in reducing the risk of contracting particular gut infections. Changes in the microbiota during an individual's lifespan are accompanied by modifications in multiple health parameters, and such observations have prompted intense scientific efforts aiming to understand the complex interactions between the microbiota and its human host, as well as how this may be influenced by diet. © 2016 The British Dietetic Association Ltd.

Expression and purification of myristoylated matrix protein of Mason-Pfizer monkey virus for NMR and MS measurements.

PubMed

Prchal, Jan; Junkova, Petra; Strmiskova, Miroslava; Lipov, Jan; Hynek, Radovan; Ruml, Tomas; Hrabal, Richard

2011-09-01

Matrix proteins play multiple roles both in early and late stages of the viral replication cycle. Their N-terminal myristoylation is important for interaction with the host cell membrane during virus budding. We used Escherichia coli, carrying N-myristoyltransferase gene, for the expression of the myristoylated His-tagged matrix protein of Mason-Pfizer monkey virus. An efficient, single-step purification procedure eliminating all contaminating proteins including, importantly, the non-myristoylated matrix protein was designed. The comparison of NMR spectra of matrix protein with its myristoylated form revealed substantial structural changes induced by this fatty acid modification. Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical constituents of Baeckea frutescens leaves inhibit copper-induced low-density lipoprotein oxidation.

PubMed

Kamiya, Kohei; Satake, Toshiko

2010-04-01

Oxidative modification of LDL plays an important role in the genesis of arteriosclerosis. This study focused on the effects of the leaves of Baeckea frutescens in the prevention of arteriosclerosis. The leaves of B. frutescens have afforded, besides known flavonoid and chromone glycosides, a novel biflavonoid glycoside, characterized as 3-O-alpha-L-rhamnopyranosylmyricetinyl-(I-2'',II-2'')-3-O-alpha-L-rhamnopyranosylmyricetin on the basis of chemical and spectral evidence. This compound exhibited marked inhibition of copper-induced LDL oxidation. Copyright (c) 2009 Elsevier B.V. All rights reserved.

S-Nitrosylation: NO-Related Redox Signaling to Protect Against Oxidative Stress

PubMed Central

STEENBERGEN, CHARLES; MURPHY, ELIZABETH

2007-01-01

Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S>-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative stress and the resultant dysfunction of NO signaling have been implicated in the pathogenesis of cardiovascular diseases. PMID:16987022

Role of miRNAs and their potential to be useful as diagnostic and prognostic biomarkers in gastric cancer

PubMed Central

da Silva Oliveira, Kelly Cristina; Thomaz Araújo, Taíssa Maíra; Albuquerque, Camila Inagaki; Barata, Gabriela Alcantara; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Rodrigues Mello Junior, Fernando Augusto; Khayat, André Salim; de Assumpção, Paulo Pimentel; Rodriguez Burbano, Rommel Mário; Smith, Marília Cardoso; Calcagno, Danielle Queiroz

2016-01-01

Alterations in epigenetic control of gene expression play an important role in many diseases, including gastric cancer. Many studies have identified a large number of upregulated oncogenic miRNAs and downregulated tumour-suppressor miRNAs in this type of cancer. In this review, we provide an overview of the role of miRNAs, pointing to their potential to be useful as diagnostic and/or prognostic biomarkers in gastric cancer. Moreover, we discuss the influence of polymorphisms and epigenetic modifications on miRNA activity. PMID:27672290

Epigenetic mechanisms: critical contributors to long-term memory formation.

PubMed

Lubin, Farah D; Gupta, Swati; Parrish, R Ryley; Grissom, Nicola M; Davis, Robin L

2011-12-01

Recent advances in chromatin biology have identified a role for epigenetic mechanisms in the regulation of neuronal gene expression changes, a necessary process for proper synaptic plasticity and memory formation. Experimental evidence for dynamic chromatin remodeling influencing gene transcription in postmitotic neurons grew from initial reports describing posttranslational modifications of histones, including phosphorylation and acetylation occurring in various brain regions during memory consolidation. An accumulation of recent studies, however, has also highlighted the importance of other epigenetic modifications, such as DNA methylation and histone methylation, as playing a role in memory formation. This present review examines learning-induced gene transcription by chromatin remodeling underlying long-lasting changes in neurons, with direct implications for the study of epigenetic mechanisms in long-term memory formation and behavior. Furthermore, the study of epigenetic gene regulation, in conjunction with transcription factor activation, can provide complementary lines of evidence to further understanding transcriptional mechanisms subserving memory storage.

Structural Color of Rock Dove’s Neck Feather

NASA Astrophysics Data System (ADS)

Nakamura, Eri; Yoshioka, Shinya; Kinoshita, Shuichi

2008-12-01

It is well known that some kinds of animal have surprisingly brilliant colors showing beautiful iridescence. These colors are called structural colors, and are thought to originate from optical interference caused by periodic microstructures that have sizes comparable with the wavelength of light. However, much larger structural modifications can also play an important role in the coloration mechanism. In this paper, we show through careful optical and structural investigations that the structural color of the neck feather of rock dove, Columba livia, has a very comprehensive mechanism: the thin-layer optical interference phenomenon fundamentally produces the iridescence, while the layer structure is accompanied by various kinds of larger-size structural modifications that control the angular range of the reflection. Further, it is found that the granules containing melanin pigment exist in a localized manner to effectively enhance the contrast of the color caused by optical interference.

Quinine conjugates and quinine analogues as potential antimalarial agents.

PubMed

Jones, Rachel A; Panda, Siva S; Hall, C Dennis

2015-06-05

Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Recent structural and mechanistic insights into post-translational enzymatic glycosylation.

PubMed

Hurtado-Guerrero, Ramon; Davies, Gideon J

2012-12-01

Enzymatic glycosylation of proteins, a post-transitional modification of great significance, is carried out by diverse glycosyltransferases (GTs) that harness activated sugar donors, typically nucleotide or lipid-phosphate linked species. Recent work has seen a major increase in the study of the 3D structure and reaction mechanism of these enzymes. Key advances include the dissection of the classical O-glycosylating and N-glycosylating apparatus, revealing unusual folds and hitherto unconsidered chemical mechanisms for acceptor activation. There has been considerable success in the application of kinetic isotope effects and quantum simulations to address the controversial issue of the reaction mechanism of retaining GTs. New roles for old modifications, exemplified by potential epigenetic roles for glycosylation, have been discovered and there has also been a plethora of studies into important mammalian glycosylations that play key roles in cellular biology, opening up new targets for chemical intervention approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation

PubMed Central

Fuchs, Gilad; Shema, Efrat; Vesterman, Rita; Kotler, Eran; Wolchinsky, Zohar; Wilder, Sylvia; Golomb, Lior; Pribluda, Ariel; Zhang, Feng; Haj-Yahya, Mahmood; Feldmesser, Ester; Brik, Ashraf; Yu, Xiaochun; Hanna, Jacob; Aberdam, Daniel; Domany, Eytan; Oren, Moshe

2012-01-01

Summary Embryonic stem cells (ESC) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. PMID:22681888

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

PubMed Central

Liao, Hsin-Wei; Hsu, Jung-Mao; Xia, Weiya; Wang, Hung-Ling; Wang, Ying-Nai; Chang, Wei-Chao; Arold, Stefan T.; Chou, Chao-Kai; Tsou, Pei-Hsiang; Yamaguchi, Hirohito; Fang, Yueh-Fu; Lee, Hong-Jen; Lee, Heng-Huan; Tai, Shyh-Kuan; Yang, Mhu-Hwa; Morelli, Maria P.; Sen, Malabika; Ladbury, John E.; Chen, Chung-Hsuan; Grandis, Jennifer R.; Kopetz, Scott; Hung, Mien-Chie

2015-01-01

Posttranslational modifications to the intracellular domain of the EGFR are known to regulate EGFR functions; however, modifications to the extracellular domain and their effects remain relatively unexplored. Here, we determined that methylation at R198 and R200 of the EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) enhances binding to EGF and subsequent receptor dimerization and signaling activation. In a mouse orthotopic colorectal cancer xenograft model, expression of a methylation-defective EGFR reduced tumor growth. Moreover, increased EGFR methylation sustained signaling activation and cell proliferation in the presence of the therapeutic EGFR monoclonal antibody cetuximab. In colorectal cancer patients, EGFR methylation level also correlated with a higher recurrence rate after cetuximab treatment and reduced overall survival. Together, these data indicate that R198/R200 methylation of the EGFR plays an important role in regulating EGFR functionality and resistance to cetuximab treatment. PMID:26571401

Regulation of parkin and PINK1 by neddylation

PubMed Central

Choo, Yeun Su; Vogler, Georg; Wang, Danling; Kalvakuri, Sreehari; Iliuk, Anton; Tao, W. Andy; Bodmer, Rolf; Zhang, Zhuohua

2012-01-01

Neddylation is a posttranslational modification that plays important roles in regulating protein structure and function by covalently conjugating NEDD8, an ubiquitin-like small molecule, to the substrate. Here, we report that Parkinson's disease (PD)-related parkin and PINK1 are NEDD8 conjugated. Neddylation of parkin and PINK1 results in increased E3 ligase activity of parkin and selective stabilization of the 55 kDa PINK1 fragment. Expression of dAPP-BP1, a NEDD8 activation enzyme subunit, in Drosophila suppresses abnormalities induced by dPINK1 RNAi. PD neurotoxin MPP+ inhibits neddylation of both parkin and PINK1. NEDD8 immunoreactivity is associated with Lewy bodies in midbrain dopaminergic neurons of PD patients. Together, these results suggest that parkin and PINK1 are regulated by neddylation and that impaired NEDD8 modification of these proteins likely contributes to PD pathogenesis. PMID:22388932

A Numerical Model Study of Nocturnal Drainage Flows with Strong Wind and Temperature Gradients.

NASA Astrophysics Data System (ADS)

Yamada, T.; Bunker, S.

1989-07-01

A second-moment turbulence-closure model described in Yamada and Bunker is used to simulate nocturnal drainage flows observed during the 1984 ASCOT field expedition in Brush Creek, Colorado. In order to simulate the observed strong wind directional shear and temperature gradients, two modifications are added to the model. The strong wind directional shear was maintained by introducing a `nudging' term in the equation of motion to guide the modeled winds in the layers above the ridge top toward the observed wind direction. The second modification was accomplished by reformulating the conservation equation for the potential temperature in such a way that only the deviation from the horizontally averaged value was prognostically computed.The vegetation distribution used in this study is undoubtedly crude. Nevertheless, the present simulation suggests that tall tree canopy can play an important role in producing inhomogeneous wind distribution, particularly in the levels below the canopy top.

Total chemical synthesis of modified histones

NASA Astrophysics Data System (ADS)

Qi, Yun-Kun; Ai, Hua-Song; Li, Yi-Ming; Yan, Baihui

2018-02-01

In the post-genome era, epigenetics has received increasing attentions in recent years. The post-translational modifications (PTMs) of four core histones play central roles in epigenetic regulation of eukaryotic genome by either directly altering the biophysical properties of nucleosomes or by recruiting other effector proteins. In order to study the biological functions and structural mechanisms of these histone PTMs, an obligatory step is to prepare a sufficient amount of homogeneously modified histones. This task cannot be fully accomplished either by recombinant technology or enzymatic modification. In this context, synthetic chemists have developed novel protein synthetic tools and state-of-the-art chemical ligation strategies for the preparation of homologous modified histones. In this review, we summarize the recent advances in the preparation of modified histones, focusing on the total chemical synthesis strategies. The importance and potential of synthetic chemistry for the study of histone code will be also discussed.

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

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

Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.

ABSTRACT Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggestmore » that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.« less

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

DOE PAGES

Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.; ...

2017-11-28

ABSTRACT Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggestmore » that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.« less

Regulation of Cell Physiology and Pathology by Protein S-Glutathionylation: Lessons Learned from the Cardiovascular System

PubMed Central

Pimentel, David; Haeussler, Dagmar Johanna; Matsui, Reiko; Burgoyne, Joseph Robert; Cohen, Richard Alan

2012-01-01

Abstract Significance: Reactive oxygen and nitrogen species contributing to homeostatic regulation and the pathogenesis of various cardiovascular diseases, including atherosclerosis, hypertension, endothelial dysfunction, and cardiac hypertrophy, is well established. The ability of oxidant species to mediate such effects is in part dependent on their ability to induce specific modifications on particular amino acids, which alter protein function leading to changes in cell signaling and function. The thiol containing amino acids, methionine and cysteine, are the only oxidized amino acids that undergo reduction by cellular enzymes and are, therefore, prime candidates in regulating physiological signaling. Various reports illustrate the significance of reversible oxidative modifications on cysteine thiols and their importance in modulating cardiovascular function and physiology. Recent Advances: The use of mass spectrometry, novel labeling techniques, and live cell imaging illustrate the emerging importance of reversible thiol modifications in cellular redox signaling and have advanced our analytical abilities. Critical Issues: Distinguishing redox signaling from oxidative stress remains unclear. S-nitrosylation as a precursor of S-glutathionylation is controversial and needs further clarification. Subcellular distribution of glutathione (GSH) may play an important role in local regulation, and targeted tools need to be developed. Furthermore, cellular redundancies of thiol metabolism complicate analysis and interpretation. Future Directions: The development of novel pharmacological analogs that specifically target subcellular compartments of GSH to promote or prevent local protein S-glutathionylation as well as the establishment of conditional gene ablation and transgenic animal models are needed. Antioxid. Redox Signal. 16, 524–542. PMID:22010840

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika

2017-01-01

Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061

The role of play objects and object play in human cognitive evolution and innovation.

PubMed

Riede, Felix; Johannsen, Niels N; Högberg, Anders; Nowell, April; Lombard, Marlize

2018-01-01

In this contribution, we address a major puzzle in the evolution of human material culture: If maturing individuals just learn their parental generation's material culture, then what is the origin of key innovations as documented in the archeological record? We approach this question by coupling a life-history model of the costs and benefits of experimentation with a niche-construction perspective. Niche-construction theory suggests that the behavior of organisms and their modification of the world around them have important evolutionary ramifications by altering developmental settings and selection pressures. Part of Homo sapiens' niche is the active provisioning of children with play objects - sometimes functional miniatures of adult tools - and the encouragement of object play, such as playful knapping with stones. Our model suggests that salient material culture innovation may occur or be primed in a late childhood or adolescence sweet spot when cognitive and physical abilities are sufficiently mature but before the full onset of the concerns and costs associated with reproduction. We evaluate the model against a series of archeological cases and make suggestions for future research. © 2018 The Authors Evolutionary Anthropology Published by Wiley Periodicals, Inc.

EG-03EXPRESSION OF PRMT5 CORRELATES WITH MALIGNANT GRADE IN GLIOMAS AND PLAYS A PIVOTAL ROLE IN TUMOR GROWTH

PubMed Central

Han, Xiaosi; Li, Rong; Zhang, Wenbin; Yang, Xiuhua; Fathallah-Shaykh, Hassan; Gillespie, Yancey; Nabors, Burt

2014-01-01

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of ω-NG,N′G-symmetric dimethylarginine residues on histones as well as other proteins. The modification play an important role in cell differentiation and tumor cell growth. However, the role of PRMT5 in human glioma cells has not been characterized. In this study, we assessed protein expression profiles of PRMT5 in control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial cells in control brain tissues and low grade astrocytomas. Its expression increased in parallel with malignant progression, and was highly expressed in GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and significantly repressed the clonogenic potential and viability of glioma cells. These findings indicate that PRMT5 is a marker of malignant progression in glioma tumors and plays a pivotal role in tumor growth.

Role of Achiral Nucleobases in Multicomponent Chiral Self-Assembly: Purine-Triggered Helix and Chirality Transfer.

PubMed

Deng, Ming; Zhang, Li; Jiang, Yuqian; Liu, Minghua

2016-11-21

Chiral self-assembly is a basic process in biological systems, where many chiral biomolecules such as amino acids and sugars play important roles. Achiral nucleobases usually covalently bond to saccharides and play a significant role in the formation of the double helix structure. However, it remains unclear how the achiral nucleobases can function in chiral self-assembly without the sugar modification. Herein, we have clarified that purine nucleobases could trigger N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to self-assemble into helical nanostructures. Moreover, the helical nanostructure could serve as a matrix and transfer the chirality to an achiral fluorescence probe, thioflavin T (ThT). Upon chirality transfer, the ThT showed not only supramolecular chirality but also circular polarized fluorescence (CPL). Without the nucleobase, the self-assembly processes cannot happen, thus providing an example where achiral molecules played an essential role in the expression and transfer of the chirality. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modulating macrophage polarization with divalent cations in nanostructured titanium implant surfaces

NASA Astrophysics Data System (ADS)

Lee, Chung-Ho; Kim, Youn-Jeong; Jang, Je-Hee; Park, Jin-Woo

2016-02-01

Nanoscale topographical modification and surface chemistry alteration using bioactive ions are centrally important processes in the current design of the surface of titanium (Ti) bone implants with enhanced bone healing capacity. Macrophages play a central role in the early tissue healing stage and their activity in response to the implant surface is known to affect the subsequent healing outcome. Thus, the positive modulation of macrophage phenotype polarization (i.e. towards the regenerative M2 rather than the inflammatory M1 phenotype) with a modified surface is essential for the osteogenesis funtion of Ti bone implants. However, relatively few advances have been made in terms of modulating the macrophage-centered early healing capacity in the surface design of Ti bone implants for the two important surface properties of nanotopography and and bioactive ion chemistry. We investigated whether surface bioactive ion modification exerts a definite beneficial effect on inducing regenerative M2 macrophage polarization when combined with the surface nanotopography of Ti. Our results indicate that nanoscale topographical modification and surface bioactive ion chemistry can positively modulate the macrophage phenotype in a Ti implant surface. To the best of our knowledge, this is the first demonstration that chemical surface modification using divalent cations (Ca and Sr) dramatically induces the regenerative M2 macrophage phenotype of J774.A1 cells in nanostructured Ti surfaces. In this study, divalent cation chemistry regulated the cell shape of adherent macrophages and markedly up-regulated M2 macrophage phenotype expression when combined with the nanostructured Ti surface. These results provide insight into the surface engineering of future Ti bone implants that are harmonized between the macrophage-governed early wound healing process and subsequent mesenchymal stem cell-centered osteogenesis function.

Chromatin immunoprecipitation (ChIP) method for non-model fruit flies (Diptera: Tephritidae) and evidence of histone modifications.

PubMed

Nagalingam, Kumaran; Lorenc, Michał T; Manoli, Sahana; Cameron, Stephen L; Clarke, Anthony R; Dudley, Kevin J

2018-01-01

Interactions between DNA and proteins located in the cell nucleus play an important role in controlling physiological processes by specifying, augmenting and regulating context-specific transcription events. Chromatin immunoprecipitation (ChIP) is a widely used methodology to study DNA-protein interactions and has been successfully used in various cell types for over three decades. More recently, by combining ChIP with genomic screening technologies and Next Generation Sequencing (e.g. ChIP-seq), it has become possible to profile DNA-protein interactions (including covalent histone modifications) across entire genomes. However, the applicability of ChIP-chip and ChIP-seq has rarely been extended to non-model species because of a number of technical challenges. Here we report a method that can be used to identify genome wide covalent histone modifications in a group of non-model fruit fly species (Diptera: Tephritidae). The method was developed by testing and refining protocols that have been used in model organisms, including Drosophila melanogaster. We demonstrate that this method is suitable for a group of economically important pest fruit fly species, viz., Bactrocera dorsalis, Ceratitis capitata, Zeugodacus cucurbitae and Bactrocera tryoni. We also report an example ChIP-seq dataset for B. tryoni, providing evidence for histone modifications in the genome of a tephritid fruit fly for the first time. Since tephritids are major agricultural pests globally, this methodology will be a valuable resource to study taxa-specific evolutionary questions and to assist with pest management. It also provides a basis for researchers working with other non-model species to undertake genome wide DNA-protein interaction studies.

Parametric Study of Amorphous High-Entropy Alloys formation from two New Perspectives: Atomic Radius Modification and Crystalline Structure of Alloying Elements

NASA Astrophysics Data System (ADS)

Hu, Q.; Guo, S.; Wang, J. M.; Yan, Y. H.; Chen, S. S.; Lu, D. P.; Liu, K. M.; Zou, J. Z.; Zeng, X. R.

2017-01-01

Chemical and topological parameters have been widely used for predicting the phase selection in high-entropy alloys (HEAs). Nevertheless, previous studies could be faulted due to the small number of available data points, the negligence of kinetic effects, and the insensitivity to small compositional changes. Here in this work, 92 TiZrHfM, TiZrHfMM, TiZrHfMMM (M = Fe, Cr, V, Nb, Al, Ag, Cu, Ni) HEAs were prepared by melt spinning, to build a reliable and sufficiently large material database to inspect the robustness of previously established parameters. Modification of atomic radii by considering the change of local electronic environment in alloys, was critically found out to be superior in distinguishing the formation of amorphous and crystalline alloys, when compared to using atomic radii of pure elements in topological parameters. Moreover, crystal structures of alloying element were found to play an important role in the amorphous phase formation, which was then attributed to how alloying hexagonal-close-packed elements and face-centered-cubic or body-centered-cubic elements can affect the mixing enthalpy. Findings from this work not only provide parametric studies for HEAs with new and important perspectives, but also reveal possibly a hidden connection among some important concepts in various fields.

Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide analogue.

PubMed

Scuotto, M; Persico, M; Bucci, M; Vellecco, V; Borbone, N; Morelli, E; Oliviero, G; Novellino, E; Piccialli, G; Cirino, G; Varra, M; Fattorusso, C; Mayol, L

2014-07-28

Herein, we report optically pure modified acyclic nucleosides as ideal probes for aptamer modification. These new monomers offer unique advantages in exploring the role played in thrombin inhibition by a single residue modification at key positions of the TBA structure.

The tomato UV-damaged DNA binding protein 1 (DDB1) plays a role in organ size control via an epigenetic manner

USDA-ARS?s Scientific Manuscript database

Epigenetic regulation, including various covalent modifications of histone proteins and methylation of cytosine bases in DNA, participates broadly in many fundamentally physiological and developmental processes. The repressed or active states of transcription resulted from epigenetic modifications a...

Histone methyltransferase Dot1L plays a role in postembryonic development in Xenopus tropicalis

PubMed Central

Wen, Luan; Fu, Liezhen; Guo, Xiaogang; Chen, Yonglong; Shi, Yun-Bo

2015-01-01

Histone methylations have been implicated to play important roles in diverse cellular processes. Of particular interest is the methylation of histone H3K79, which is catalyzed by an evolutionarily conserved methyltransferase, disruptor of telomeric silencing (Dot1)-like (Dot1L). To investigate the role of Dot1L during vertebrate development, we have generated a Dot1L-specific transcription activator-like effector nuclease (TALEN) nuclease to knockdown endogenous Dot1L in Xenopus tropicalis, a diploid species highly related to the well-known developmental model Xenopus laevis, a pseudotetraploid amphibian. We show that the TALEN was extremely efficient in mutating Dot1L when expressed in fertilized eggs, creating essentially Dot1L knockout embryos with little H3K79 methylation. Importantly, we observed that Dot1L knockdown had no apparent effect on embryogenesis because normally feeding tadpoles were formed, consistent with the lack of maternal Dot1L expression. On the other hand, Dot1L knockdown severely retarded the growth of the tadpoles and led to tadpole lethality prior to metamorphosis. These findings suggest that Dot1L and H3K79 methylation play an important role for tadpole growth and development prior to metamorphosis into a frog. Our findings further reveal interesting similarities and differences between Xenopus and mouse development and suggest the existence of 2 separate phases of vertebrate development with distinct requirements for epigenetic modifications.—Wen, L., Fu, L., Guo, X., Chen, Y., Shi, Y.-B. Histone methyltransferase Dot1L plays a role in postembryonic development in Xenopus tropicalis. PMID:25366346

Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-κB-dependent Genes

PubMed Central

Sundar, Isaac K.; Chung, Sangwoon; Hwang, Jae-woong; Lapek, John D.; Bulger, Michael; Friedman, Alan E.; Yao, Hongwei; Davie, James R.; Rahman, Irfan

2012-01-01

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase-dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-κB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-κB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-κB activation and chromatin modifications, which have implications in pathogenesis of COPD. PMID:22312446

Ambient water and visible-light irradiation drive changes in graphene morphology, structure, surface chemistry, aggregation, and toxicity.

PubMed

Hu, Xiangang; Zhou, Ming; Zhou, Qixing

2015-03-17

The environmental behaviors and risks associated with graphene have attracted considerable attention. However, the fundamental effects of ambient water and visible-light irradiation on the properties and toxicity of graphene remain unknown. This work revealed that hydration and irradiation result in the transformation of large-sheet graphene to long-ribbon graphene. The thickness of the treated graphene decreased, and oxides were formed through the generation of singlet oxygen. In addition, hydration and irradiation resulted in greater disorder in the graphene structure and in the expansion of the d-spacing of the structure due to the introduction of water molecules and modifications of the functional groups. Oxidative modifications with two-stage (fast and low) kinetics enhanced the number of negative surface charges on the graphene and enhanced graphene aggregation. The above property alterations reduced the nanotoxicity of graphene to algal cells by reducing the generation of reactive oxygen species, diminishing protein carbonylation and decreasing tail DNA. A comparative study using graphene oxide suggested that oxidative modifications could play an important role in inhibiting toxicological activity. This study provides a preliminary approach for understanding the environmental behaviors of graphene and avoids overestimating the risks of graphene in the natural environment.

An in-situ synthesis of Ag/AgCl/TiO2/hierarchical porous magnesian material and its photocatalytic performance

PubMed Central

Yang, Lu; Wang, Fazhou; Shu, Chang; Liu, Peng; Zhang, Wenqin; Hu, Shuguang

2016-01-01

The absorption ability and photocatalytic activity of photocatalytic materials play important roles in improving the pollutants removal effects. Herein, we reported a new kind of photocatalytic material, which was synthesized by simultaneously designing hierarchical porous magnesian (PM) substrate and TiO2 catalyst modification. Particularly, PM substrate could be facilely prepared by controlling its crystal phase (Phase 5, Mg3Cl(OH)5·4H2O), while Ag/AgCl particles modification of TiO2 could be achieved by in situ ion exchange between Ag+ and above crystal Phase. Physiochemical analysis shows that Ag/AgCl/TiO2/PM material has higher visible and ultraviolet light absorption response, and excellent gas absorption performance compared to other controls. These suggested that Ag/AgCl/TiO2/PM material could produce more efficient photocatalytic effects. Its photocatalytic reaction rate was 5.21 and 30.57 times higher than that of TiO2/PM and TiO2/imporous magnesian substrate, respectively. Thus, this material and its intergration synthesis method could provide a novel strategy for high-efficiency application and modification of TiO2 photocatalyst in engineering filed. PMID:26883972

Epigenetic: a molecular link between testicular cancer and environmental exposures.

PubMed

Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A; Volle, David H

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Epigenetic: a molecular link between testicular cancer and environmental exposures

PubMed Central

Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A.; Volle, David H.

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures. PMID:23230429

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

PubMed

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficiency of plasma actuator ionization in shock wave modification in a rarefied supersonic flow over a flat plate

NASA Astrophysics Data System (ADS)

Joussot, Romain; Lago, Viviana; Parisse, Jean-Denis

2014-12-01

This paper describes experimental and numerical investigations focused on the shock wave modification, induced by a dc glow discharge, of a Mach 2 flow under rarefied regime. The model under investigation is a flat plate equipped with a plasma actuator composed of two electrodes. The glow discharge is generated by applying a negative potential to the upstream electrode, enabling the creation of a weakly ionized plasma. The natural flow (i.e. without the plasma) exhibits a thick laminar boundary layer and a shock wave with a hyperbolic shape. Images of the flow obtained with an ICCD camera revealed that the plasma discharge induces an increase in the shock wave angle. Thermal effects (volumetric, and at the surface) and plasma effects (ionization, and thermal non-equilibrium) are the most relevant processes explaining the observed modifications. The effect induced by the heating of the flat plate surface is studied experimentally by replacing the upstream electrode by a heating element, and numerically by modifying the thermal boundary condition of the model surface. The results show that for a similar temperature distribution over the plate surface, modifications induced by the heating element are lower than those produced by the plasma. This difference shows that other effects than purely thermal effects are involved with the plasma actuator. Measurements of the electron density with a Langmuir probe highlight the fact that the ionization degree plays an important role into the modification of the flow. The gas properties, especially the isentropic exponent, are indeed modified by the plasma above the actuator and upstream the flat plate. This leads to a local modification of the flow conditions, inducing an increase in the shock wave angle.

A Novel Post-translational Modification of Nucleolin, SUMOylation at Lys-294, Mediates Arsenite-induced Cell Death by Regulating gadd45α mRNA Stability*

PubMed Central

Zhang, Dongyun; Liang, Yuguang; Xie, Qipeng; Gao, Guangxun; Wei, Jinlong; Huang, Haishan; Li, Jingxia; Gao, Jimin; Huang, Chuanshu

2015-01-01

Nucleolin is a ubiquitously expressed protein and participates in many important biological processes, such as cell cycle regulation and ribosomal biogenesis. The activity of nucleolin is regulated by intracellular localization and post-translational modifications, including phosphorylation, methylation, and ADP-ribosylation. Small ubiquitin-like modifier (SUMO) is a category of recently verified forms of post-translational modifications and exerts various effects on the target proteins. In the studies reported here, we discovered SUMOylational modification of human nucleolin protein at Lys-294, which facilitated the mRNA binding property of nucleolin by maintaining its nuclear localization. In response to arsenic exposure, nucleolin-SUMO was induced and promoted its binding with gadd45α mRNA, which increased gadd45α mRNA stability and protein expression, subsequently causing GADD45α-mediated cell death. On the other hand, ectopic expression of Mn-SOD attenuated the arsenite-generated superoxide radical level, abrogated nucleolin-SUMO, and in turn inhibited arsenite-induced apoptosis by reducing GADD45α expression. Collectively, our results for the first time demonstrate that nucleolin-SUMO at K294R plays a critical role in its nucleus sequestration and gadd45α mRNA binding activity. This novel biological function of nucleolin is distinct from its conventional role as a proto-oncogene. Therefore, our findings here not only reveal a new modification of nucleolin protein and its novel functional paradigm in mRNA metabolism but also expand our understanding of the dichotomous roles of nucleolin in terms of cancer development, which are dependent on multiple intracellular conditions and consequently the appropriate regulations of its modifications, including SUMOylation. PMID:25561743

Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations

PubMed Central

Jiang, Jun; Aduri, Raviprasad; Chow, Christine S.; SantaLucia, John

2014-01-01

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson–Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity. PMID:24371282

The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

PubMed Central

Zheng, Liming; Zhai, Yuanxin; Li, Na; Ma, Fanglin; Zhu, Haijing; Du, Xiaomin; Li, Guangpeng; Hua, Jinlian

2016-01-01

Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock. In our study, we not only analyzed the morphology, gene expression, DNA methylation and histone methylation dynamic in mouse Tet1 (mTet1) modified mGSCs, we also analyzed the stemness ability by in vivo transplantation and explored the functional mechanism of Tet1 in dairy goat mGSCs. The results showed mTet1 modified mGSCs had better self-renewal and proliferation ability than wild-type mGSCs, mTet1 could also up-regulate JMJD3 to decrease H3K27me3, which also showed to suppress the MEK-ERK pathway. Furthermore, Co-IP analysis demonstrated that TET1 interact with PCNA and HDAC1 by forming protein complexes to comprehensively regulate dairy goat mGSCs and spermatogenesis. PMID:27857213

Modified Amber Force Field Correctly Models the Conformational Preference for Tandem GA pairs in RNA

PubMed Central

2015-01-01

Molecular mechanics with all-atom models was used to understand the conformational preference of tandem guanine-adenine (GA) noncanonical pairs in RNA. These tandem GA pairs play important roles in determining stability, flexibility, and structural dynamics of RNA tertiary structures. Previous solution structures showed that these tandem GA pairs adopt either imino (cis Watson–Crick/Watson–Crick A-G) or sheared (trans Hoogsteen/sugar edge A-G) conformations depending on the sequence and orientation of the adjacent closing base pairs. The solution structures (GCGGACGC)2 [Biochemistry, 1996, 35, 9677–9689] and (GCGGAUGC)2 [Biochemistry, 2007, 46, 1511–1522] demonstrate imino and sheared conformations for the two central GA pairs, respectively. These systems were studied using molecular dynamics and free energy change calculations for conformational changes, using umbrella sampling. For the structures to maintain their native conformations during molecular dynamics simulations, a modification to the standard Amber ff10 force field was required, which allowed the amino group of guanine to leave the plane of the base [J. Chem. Theory Comput., 2009, 5, 2088–2100] and form out-of-plane hydrogen bonds with a cross-strand cytosine or uracil. The requirement for this modification suggests the importance of out-of-plane hydrogen bonds in stabilizing the native structures. Free energy change calculations for each sequence demonstrated the correct conformational preference when the force field modification was used, but the extent of the preference is underestimated. PMID:24803859

Providing Public Space Continuities in Post-Industrial Areas through Remodelling Land/Water Connections

NASA Astrophysics Data System (ADS)

Burda, Izabela M.; Nyka, Lucyna

2017-10-01

This article examines the problem of urban transformation strategies applied in recent years which are based on the creation of new water areas and modification of existing ones. The research is an attempt to prove that modifications of plans of water areas and forms of their borders may play an important role in achieving the best quality public spaces in post-industrial territories. The basis for demonstrating the importance of modifying water borders, and introducing new forms of water-based structures in cities, are theoretical surveys, comparative studies and in-field analyses. It can be seen that post-industrial areas, which used to create voids in the urban fabric, can be perceived as unique but isolated places that should be integrated into the layout of cities. Thus, creating continuity of public spaces that will relate converted areas to their surroundings is a well-known objective of many transformation strategies. This research proves that an effective strategy toward achieving this goal can be based on the modification of relationships between land and water. Namely, the introduction of new water areas, designing new pieces of land that protrude into the water, softening the boundaries of water lines or the opposite, like structuring smaller water flows into well-defined canals, may significantly contribute to the quality of public spaces. As such, all of this fosters the development of sustainable cities and contributes significantly to the emergence of high-quality urban landscapes.

SUMOylation in Neurological Diseases.

PubMed

Liu, F-Y; Liu, Y-F; Yang, Y; Luo, Z-W; Xiang, J-W; Chen, Z-G; Qi, R-L; Yang, T-H; Xiao, Y; Qing, W-J; Li, D W-C

2017-01-01

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antibody-free PRISM-SRM for multiplexed protein quantification: Is this the new competition for immunoassays in bioanalysis?

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

Shi, Tujin; Qian, Weijun

2013-02-01

Highly sensitive technologies for multiplexed quantification of a large number of candidate proteins will play an increasingly important role in clinical biomarker discovery, systems biology, and general biomedical research. Herein we introduce the new PRISM-SRM technology, which represents a highly sensitive multiplexed quantification technology capable of simultaneous quantification of many low-abundance proteins without the need of affinity reagents. The versatility of antibody-free PRISM-SRM for quantifying various types of targets including protein isoforms, protein modifications, metabolites, and others, thus offering new competition with immunoassays.

Career development resource: academic career in surgical education.

PubMed

Sanfey, Hilary; Gantt, Nancy L

2012-07-01

Academic surgeons play an instrumental role in the training of our medical students and surgical residents. Although volunteer faculty often have an important role in the clinical development of surgeons-in-training, the tasks of curricular development, structured didactic sessions, professional advising, research sponsorship, and mentoring at all levels fall to the academic surgeon. Historically, the career advancement path for an academic physician favored grant acquisition and scholarly publication. Broader definitions of scholarship have emerged, along with corresponding modifications in academic award systems that allow advancement in faculty rank based on a surgeon's educational efforts. Copyright © 2012 Elsevier Inc. All rights reserved.

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

Protein palmitoylation plays an important role in Trichomonas vaginalis adherence.

PubMed

Nievas, Yesica R; Vashisht, Ajay A; Corvi, Maria M; Metz, Sebastian; Johnson, Patricia J; Wohlschlegel, James A; de Miguel, Natalia

2018-02-14

The flagellated protozoan parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. As an obligate extracellular pathogen, adherence to epithelial cells is critical for parasite survival within the human host and a better understanding of this process is a prerequisite for the development of therapies to combat infection. In this sense, recent work has shown S-acylation as a key modification that regulates pathogenesis in different protozoan parasites. However, there are no reports indicating whether this post-translational modification is a mechanism operating in T. vaginalis. In order to study the extent and function of S-acylation in T. vaginalis biology, we undertook a proteomic study to profile the full scope of S-acylated proteins in this parasite and reported the identification of 363 proteins involved in a variety of biological processes such as protein transport, pathogenesis related and signaling, among others. Importantly, treatment of parasites with the palmitoylation inhibitor 2-bromopalmitate causes a significant decrease in parasite: parasite aggregation as well as adherence to host cells suggesting that palmitoylation could be modifying proteins that are key regulators of Trichomonas vaginalis pathogenesis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular farming on rescue of pharma industry for next generations.

PubMed

Moustafa, Khaled; Makhzoum, Abdullah; Trémouillaux-Guiller, Jocelyne

2016-10-01

Recombinant proteins expressed in plants have been emerged as a novel branch of the biopharmaceutical industry, offering practical and safety advantages over traditional approaches. Cultivable in various platforms (i.e. open field, greenhouses or bioreactors), plants hold great potential to produce different types of therapeutic proteins with reduced risks of contamination with human and animal pathogens. To maximize the yield and quality of plant-made pharmaceuticals, crucial factors should be taken into account, including host plants, expression cassettes, subcellular localization, post-translational modifications, and protein extraction and purification methods. DNA technology and genetic transformation methods have also contributed to great parts with substantial improvements. To play their proper function and stability, proteins require multiple post-translational modifications such as glycosylation. Intensive glycoengineering research has been performed to reduce the immunogenicity of recombinant proteins produced in plants. Important strategies have also been developed to minimize the proteolysis effects and enhance protein accumulation. With growing human population and new epidemic threats, the need for new medications will be paramount so that the traditional pharmaceutical industry will not be alone to answer medication demands for upcoming generations. Here, we review several aspects of plant molecular pharming and outline some important challenges that hamper these ambitious biotechnological developments.

Gene Flow in Genetically Engineered Perennial Grasses: Lessons for Modification of Dedicated Bioenergy Crops

USDA-ARS?s Scientific Manuscript database

Genetic modification of dedicated bioenergy crops, such as switchgrass, will play a major role in crop improvement for a wide range of beneficial traits specific to biofuels. One obstacle that arises regarding transgenic improvement of perennials used for biofuels is the propensity of these plants t...

Task Modification and Knowledge Utilization by Korean Prospective Mathematics Teachers

ERIC Educational Resources Information Center

Lee, Kyeong-Hwa; Lee, Eun-Jung; Park, Min-Sun

2016-01-01

It has been asserted that mathematical tasks play a critical role in the teaching and learning of mathematics. Modification of tasks included in intended curriculum materials, such as textbooks, can be an effective activity for prospective teachers to understand the role of mathematical tasks in the teaching and learning of mathematics; designing…

Receptors and aging: dedicated to the memory of Paul Ehrlich for the 100th anniversary of his Nobel Prize.

PubMed

Robert, L; Labat-Robert, J; Robert, A M

2010-01-01

The initiation and evolution of the receptor concept and its application in pharmacology can be traced back to Paul Ehrlich's original experiments. Since several decades the receptor concept is in the foreground of cell biology and pharmacology. We present here a short reminder of Ehrlich's concepts on receptor action, its evolution and modifications as a result of increasing life expectancy of human societies. Results obtained by several teams on the age-dependent modifications of receptor function are reviewed with special emphasis on the age-dependent loss of receptors and of uncoupling of receptors from their intracellular transmission pathway. As a special example we summarize our results on the elastin receptor and its age-dependent modifications. These modifications result in the loss of the physiologically helpful functions mediated by this receptor, such as vasodilation by coupling with the inducible nitric oxide synthase (iNOS)-inhibition of cellular cholesterol synthesis and modulation of free radical production by inhibition of the guanine nucleotide binding protein (Gi protein)-mediated transmission pathway. Only the harmful effects such as free radical release and up-regulation of elastase production remain in "old" cells. The age-dependent modifications of receptor function play an important role in the increasing frequency and severity of age-related diseases such as athero-arteriosclerosis and emphysema as well as the loss of hormone- and drug actions. These processes and their inhibition or correction represent a new challenge for cellular pharmacology. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Chemical-modification studies of a unique sialic acid-binding lectin from the snail Achatina fulica. Involvement of tryptophan and histidine residues in biological activity.

PubMed Central

Basu, S; Mandal, C; Allen, A K

1988-01-01

A unique sialic acid-binding lectin, achatininH (ATNH) was purified in single step from the haemolymph of the snail Achatina fulica by affinity chromatography on sheep submaxillary-gland mucin coupled to Sepharose 4B. The homogeneity was checked by alkaline gel electrophoresis, immunodiffusion and immunoelectrophoresis. Amino acid analysis showed that the lectin has a fairly high content of acidic amino acid residues (22% of the total). About 1.3% of the residues are half-cystine. The glycoprotein contains 21% carbohydrate. The unusually high content of xylose (6%) and fucose (2.7%) in this snail lectin is quite interesting. The protein was subjected to various chemical modifications in order to detect the amino acid residues and carbohydrate residues present in its binding sites. Modification of tyrosine and arginine residues did not affect the binding activity of ATNH; however, modification of tryptophan and histidine residues led to a complete loss of its biological activity. A marked decrease in the fluorescence emission was found as the tryptophan residues of ATNH were modified. The c.d. data showed the presence of an identical type of conformation in the native and modified agglutinin. The modification of lysine and carboxy residues partially diminished the biological activity. The activity was completely lost after a beta-elimination reaction, indicating that the sugars are O-glycosidically linked to the glycoprotein's protein moiety. This result confirms that the carbohydrate moiety also plays an important role in the agglutination property of this lectin. Images Fig. 3. PMID:3140796

The Halophile protein database.

PubMed

Sharma, Naveen; Farooqi, Mohammad Samir; Chaturvedi, Krishna Kumar; Lal, Shashi Bhushan; Grover, Monendra; Rai, Anil; Pandey, Pankaj

2014-01-01

Halophilic archaea/bacteria adapt to different salt concentration, namely extreme, moderate and low. These type of adaptations may occur as a result of modification of protein structure and other changes in different cell organelles. Thus proteins may play an important role in the adaptation of halophilic archaea/bacteria to saline conditions. The Halophile protein database (HProtDB) is a systematic attempt to document the biochemical and biophysical properties of proteins from halophilic archaea/bacteria which may be involved in adaptation of these organisms to saline conditions. In this database, various physicochemical properties such as molecular weight, theoretical pI, amino acid composition, atomic composition, estimated half-life, instability index, aliphatic index and grand average of hydropathicity (Gravy) have been listed. These physicochemical properties play an important role in identifying the protein structure, bonding pattern and function of the specific proteins. This database is comprehensive, manually curated, non-redundant catalogue of proteins. The database currently contains 59 897 proteins properties extracted from 21 different strains of halophilic archaea/bacteria. The database can be accessed through link. Database URL: http://webapp.cabgrid.res.in/protein/ © The Author(s) 2014. Published by Oxford University Press.

75 FR 1269 - Vegetable Import Regulations; Modification of Potato Import Regulations; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-11

... C] Vegetable Import Regulations; Modification of Potato Import Regulations; Correction AGENCY... modified the import regulations for Irish potatoes and made minor administrative changes to the potato...

Behavior Modification of Retarded Preschool Children.

ERIC Educational Resources Information Center

Yamaguchi, Kaoru

1977-01-01

In a study of behavior modification two Down's syndrome preschool children, the first a 5-year-old boy with autistic behavior patterns and the second a 4-year-old girl whose behavior problem was to reject other children, were examined. The first S was engaged in ball catching activities with a teacher with positive reinforcement (playing the S's…

PHANTASTICA regulates leaf polarity and petiole identity in Medicago truncatula

PubMed Central

Ge, Liangfa; Chen, Rujin

2014-01-01

Establishment of proper polarities along the adaxial-abaxial, proximodistal, and medial-lateral axes is a critical step for the expansion of leaves from leaf primordia. It has been shown that the MYB domain protein, ASYMMETRIC LEAVES1/ROUGH SHEATH2/PHANTASTICA (collectively named ARP) plays an important role in this process. Loss of function of ARP leads to severe leaf polarity defects, such as abaxialized or needle-like leaves. In addition to its role in leaf polarity establishment, we have recently shown that the Medicago truncatula ARP gene, MtPHAN, also plays a role in leaf petiole identity regulation. We show that a mutation of MtPHAN results in petioles acquiring characteristics of the motor organ, pulvinus, including small epidermal cells with extensive cell surface modifications and altered vascular tissue development. Taken together, our results reveal a previously unidentified function of ARP in leaf development. PMID:24603499

Radical SAM Enzymes in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides (RiPPs).

PubMed

Benjdia, Alhosna; Balty, Clémence; Berteau, Olivier

2017-01-01

Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large and diverse family of natural products. They possess interesting biological properties such as antibiotic or anticancer activities, making them attractive for therapeutic applications. In contrast to polyketides and non-ribosomal peptides, RiPPs derive from ribosomal peptides and are post-translationally modified by diverse enzyme families. Among them, the emerging superfamily of radical SAM enzymes has been shown to play a major role. These enzymes catalyze the formation of a wide range of post-translational modifications some of them having no counterparts in living systems or synthetic chemistry. The investigation of radical SAM enzymes has not only illuminated unprecedented strategies used by living systems to tailor peptides into complex natural products but has also allowed to uncover novel RiPP families. In this review, we summarize the current knowledge on radical SAM enzymes catalyzing RiPP post-translational modifications and discuss their mechanisms and growing importance notably in the context of the human microbiota.

Femtosecond laser modification of an array of vertically aligned carbon nanotubes intercalated with Fe phase nanoparticles

PubMed Central

2013-01-01

Femtosecond lasers (FSL) are playing an increasingly important role in materials research, characterization, and modification. Due to an extremely short pulse width, interactions of FSL irradiation with solid surfaces attract special interest, and a number of unusual phenomena resulted in the formation of new materials are expected. Here, we report on a new nanostructure observed after the interaction of FSL irradiation with arrays of vertically aligned carbon nanotubes (CNTs) intercalated with iron phase catalyst nanoparticles. It was revealed that the FSL laser ablation transforms the topmost layer of CNT array into iron phase nanospheres (40 to 680 nm in diameter) located at the tip of the CNT bundles of conical shape. Besides, the smaller nanospheres (10 to 30 nm in diameter) are found to be beaded at the sides of these bundles. Some of the larger nanospheres are encapsulated into carbon shells, which sometime are found to contain CNTs. The mechanism of creation of such nanostructures is proposed. PMID:24004518

Femtosecond laser modification of an array of vertically aligned carbon nanotubes intercalated with Fe phase nanoparticles.

PubMed

Labunov, Vladimir; Prudnikava, Alena; Bushuk, Serguei; Filatov, Serguei; Shulitski, Boris; Tay, Beng Kang; Shaman, Yury; Basaev, Alexander

2013-09-03

Femtosecond lasers (FSL) are playing an increasingly important role in materials research, characterization, and modification. Due to an extremely short pulse width, interactions of FSL irradiation with solid surfaces attract special interest, and a number of unusual phenomena resulted in the formation of new materials are expected. Here, we report on a new nanostructure observed after the interaction of FSL irradiation with arrays of vertically aligned carbon nanotubes (CNTs) intercalated with iron phase catalyst nanoparticles. It was revealed that the FSL laser ablation transforms the topmost layer of CNT array into iron phase nanospheres (40 to 680 nm in diameter) located at the tip of the CNT bundles of conical shape. Besides, the smaller nanospheres (10 to 30 nm in diameter) are found to be beaded at the sides of these bundles. Some of the larger nanospheres are encapsulated into carbon shells, which sometime are found to contain CNTs. The mechanism of creation of such nanostructures is proposed.

Nanotubular topography enhances the bioactivity of titanium implants.

PubMed

Huang, Jingyan; Zhang, Xinchun; Yan, Wangxiang; Chen, Zhipei; Shuai, Xintao; Wang, Anxun; Wang, Yan

2017-08-01

Surface modification on titanium implants plays an important role in promoting mesenchymal stem cell (MSC) response to enhance osseointegration persistently. In this study, nano-scale TiO 2 nanotube topography (TNT), micro-scale sand blasted-acid etched topography (SLA), and hybrid sand blasted-acid etched/nanotube topography (SLA/TNT) were fabricated on the surfaces of titanium implants. Although the initial cell adherence at 60 min among TNT, SLA and TNT/SLA was not different, SLA and SLA/TNT presented to be rougher and suppressed the proliferation of MSC. TNT showed hydrophilic surface and balanced promotion of cellular functions. After being implanted in rabbit femur models, TNT displayed the best osteogenesis inducing ability as well as strong bonding strength to the substrate. These results indicate that nano-scale TNT provides favorable surface topography for improving the clinical performance of endosseous implants compared with micro and hybrid micro/nano surfaces, suggesting a promising and reliable surface modification strategy of titanium implants for clinical application. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein.

PubMed

Liger, Dominique; Mora, Liliana; Lazar, Noureddine; Figaro, Sabine; Henri, Julien; Scrima, Nathalie; Buckingham, Richard H; van Tilbeurgh, Herman; Heurgué-Hamard, Valérie; Graille, Marc

2011-08-01

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases.

Mechanism of activation of methyltransferases involved in translation by the Trm112 ‘hub’ protein

PubMed Central

Liger, Dominique; Mora, Liliana; Lazar, Noureddine; Figaro, Sabine; Henri, Julien; Scrima, Nathalie; Buckingham, Richard H.; van Tilbeurgh, Herman; Heurgué-Hamard, Valérie; Graille, Marc

2011-01-01

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases. PMID:21478168

A Multifeatures Fusion and Discrete Firefly Optimization Method for Prediction of Protein Tyrosine Sulfation Residues.

PubMed

Guo, Song; Liu, Chunhua; Zhou, Peng; Li, Yanling

2016-01-01

Tyrosine sulfation is one of the ubiquitous protein posttranslational modifications, where some sulfate groups are added to the tyrosine residues. It plays significant roles in various physiological processes in eukaryotic cells. To explore the molecular mechanism of tyrosine sulfation, one of the prerequisites is to correctly identify possible protein tyrosine sulfation residues. In this paper, a novel method was presented to predict protein tyrosine sulfation residues from primary sequences. By means of informative feature construction and elaborate feature selection and parameter optimization scheme, the proposed predictor achieved promising results and outperformed many other state-of-the-art predictors. Using the optimal features subset, the proposed method achieved mean MCC of 94.41% on the benchmark dataset, and a MCC of 90.09% on the independent dataset. The experimental performance indicated that our new proposed method could be effective in identifying the important protein posttranslational modifications and the feature selection scheme would be powerful in protein functional residues prediction research fields.

A Multifeatures Fusion and Discrete Firefly Optimization Method for Prediction of Protein Tyrosine Sulfation Residues

PubMed Central

Liu, Chunhua; Zhou, Peng; Li, Yanling

2016-01-01

Tyrosine sulfation is one of the ubiquitous protein posttranslational modifications, where some sulfate groups are added to the tyrosine residues. It plays significant roles in various physiological processes in eukaryotic cells. To explore the molecular mechanism of tyrosine sulfation, one of the prerequisites is to correctly identify possible protein tyrosine sulfation residues. In this paper, a novel method was presented to predict protein tyrosine sulfation residues from primary sequences. By means of informative feature construction and elaborate feature selection and parameter optimization scheme, the proposed predictor achieved promising results and outperformed many other state-of-the-art predictors. Using the optimal features subset, the proposed method achieved mean MCC of 94.41% on the benchmark dataset, and a MCC of 90.09% on the independent dataset. The experimental performance indicated that our new proposed method could be effective in identifying the important protein posttranslational modifications and the feature selection scheme would be powerful in protein functional residues prediction research fields. PMID:27034949

BGDB: a database of bivalent genes.

PubMed

Li, Qingyan; Lian, Shuabin; Dai, Zhiming; Xiang, Qian; Dai, Xianhua

2013-01-01

Bivalent gene is a gene marked with both H3K4me3 and H3K27me3 epigenetic modification in the same area, and is proposed to play a pivotal role related to pluripotency in embryonic stem (ES) cells. Identification of these bivalent genes and understanding their functions are important for further research of lineage specification and embryo development. So far, lots of genome-wide histone modification data were generated in mouse and human ES cells. These valuable data make it possible to identify bivalent genes, but no comprehensive data repositories or analysis tools are available for bivalent genes currently. In this work, we develop BGDB, the database of bivalent genes. The database contains 6897 bivalent genes in human and mouse ES cells, which are manually collected from scientific literature. Each entry contains curated information, including genomic context, sequences, gene ontology and other relevant information. The web services of BGDB database were implemented with PHP + MySQL + JavaScript, and provide diverse query functions. Database URL: http://dailab.sysu.edu.cn/bgdb/

Yeast synthetic biology for the production of recombinant therapeutic proteins.

PubMed

Kim, Hyunah; Yoo, Su Jin; Kang, Hyun Ah

2015-02-01

The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

NASA Astrophysics Data System (ADS)

Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

2016-05-01

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.

CRISPR-Mediated Epigenome Editing

PubMed Central

Enríquez, Paul

2016-01-01

Mounting evidence has called into question our understanding of the role that the central dogma of molecular biology plays in human pathology. The conventional view that elucidating the mechanisms for translating genes into proteins can account for a panoply of diseases has proven incomplete. Landmark studies point to epigenetics as a missing piece of the puzzle. However, technological limitations have hindered the study of specific roles for histone post-translational modifications, DNA modifications, and non-coding RNAs in regulation of the epigenome and chromatin structure. This feature highlights CRISPR systems, including CRISPR-Cas9, as novel tools for targeted epigenome editing. It summarizes recent developments in the field, including integration of optogenetic and functional genomic approaches to explore new therapeutic opportunities, and underscores the importance of mitigating current limitations in the field. This comprehensive, analytical assessment identifies current research gaps, forecasts future research opportunities, and argues that as epigenome editing technologies mature, overcoming critical challenges in delivery, specificity, and fidelity should clear the path to bring these technologies into the clinic. PMID:28018139

Lysosomal enzymes and their receptors in invertebrates: an evolutionary perspective.

PubMed

Kumar, Nadimpalli Siva; Bhamidimarri, Poorna M

2015-01-01

Lysosomal biogenesis is an important process in eukaryotic cells to maintain cellular homeostasis. The key components that are involved in the biogenesis such as the lysosomal enzymes, their modifications and the mannose 6-phosphate receptors have been well studied and their evolutionary conservation across mammalian and non-mammalian vertebrates is clearly established. Invertebrate lysosomal biogenesis pathway on the other hand is not well studied. Although, details on mannose 6-phosphate receptors and enzymes involved in lysosomal enzyme modifications were reported earlier, a clear cut pathway has not been established. Recent research on the invertebrate species involving biogenesis of lysosomal enzymes suggests a possible conserved pathway in invertebrates. This review presents certain observations based on these processes that include biochemical, immunological and functional studies. Major conclusions include conservation of MPR-dependent pathway in higher invertebrates and recent evidence suggests that MPR-independent pathway might have been more prominent among lower invertebrates. The possible components of MPR-independent pathway that may play a role in lysosomal enzyme targeting are also discussed here.

Influence of Chemical Composition on Rupture Properties at 1200 Degrees F. of Forged Chromium-Cobalt-Nickel-Iron Base Alloys in Solution-Treated and Aged Condition

NASA Technical Reports Server (NTRS)

Reynolds, E E; Freeman, J W; White, A E

1951-01-01

The influence of systematic variations of chemical composition on rupture properties at 1200 degrees F. was determined for 62 modifications of a basic alloy containing 20 percent chromium, 20 percent nickel, 20 percent cobalt, 3 percent molybdenum, 2 percent tungsten, 1 percent columbium, 0.15 percent carbon, 1.7 percent manganese, 0.5 percent silicon, 0.12 percent nitrogen and the balance iron. These modifications included individual variations of each of 10 elements present and simultaneous variations of molybdenum, tungsten, and columbium. Laboratory induction furnace heats were hot-forged to round bar stock, solution-treated at 2200 degrees F., and aged at 1400 degrees F. The melting and fabrication conditions were carefully controlled in order to minimize all variable effects on properties except chemical composition. Information is presented which indicates that melting and hot-working conditions play an important role in high-temperature properties of alloys of the type investigated.

CRISPR-Mediated Epigenome Editing.

PubMed

Enríquez, Paul

2016-12-01

Mounting evidence has called into question our understanding of the role that the central dogma of molecular biology plays in human pathology. The conventional view that elucidating the mechanisms for translating genes into proteins can account for a panoply of diseases has proven incomplete. Landmark studies point to epigenetics as a missing piece of the puzzle. However, technological limitations have hindered the study of specific roles for histone post-translational modifications, DNA modifications, and non-coding RNAs in regulation of the epigenome and chromatin structure. This feature highlights CRISPR systems, including CRISPR-Cas9, as novel tools for targeted epigenome editing. It summarizes recent developments in the field, including integration of optogenetic and functional genomic approaches to explore new therapeutic opportunities, and underscores the importance of mitigating current limitations in the field. This comprehensive, analytical assessment identifies current research gaps, forecasts future research opportunities, and argues that as epigenome editing technologies mature, overcoming critical challenges in delivery, specificity, and fidelity should clear the path to bring these technologies into the clinic.

Methanol Steam Reforming Promoted by Molten Salt-Modified Platinum on Alumina Catalysts

PubMed Central

Kusche, Matthias; Agel, Friederike; Ní Bhriain, Nollaig; Kaftan, Andre; Laurin, Mathias; Libuda, Jörg; Wasserscheid, Peter

2014-01-01

We herein describe a straight forward procedure to increase the performance of platinum-on-alumina catalysts in methanol steam reforming by applying an alkali hydroxide coating according to the “solid catalyst with ionic liquid layer” (SCILL) approach. We demonstrate by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed desorption (TPD) studies that potassium doping plays an important role in the catalyst activation. Moreover, the hygroscopic nature and the basicity of the salt modification contribute to the considerable enhancement in catalytic performance. During reaction, a partly liquid film of alkali hydroxides/carbonates forms on the catalyst/alumina surface, thus significantly enhancing the availability of water at the catalytically active sites. Too high catalyst pore fillings with salt introduce a considerable mass transfer barrier into the system as indicated by kinetic studies. Thus, the optimum interplay between beneficial catalyst modification and detrimental mass transfer effects had to be identified and was found on the applied platinum-on-alumina catalyst at KOH loadings around 7.5 mass %. PMID:25124120

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

Laskin, Julia; Johnson, Grant E.; Prabhakaran, Venkateshkumar

Immobilization of complex molecules and clusters on supports plays an important role in a variety of disciplines including materials science, catalysis and biochemistry. In particular, deposition of clusters on surfaces has attracted considerable attention due to their non-scalable, highly size-dependent properties. The ability to precisely control the composition and morphology of clusters and small nanoparticles on surfaces is crucial for the development of next generation materials with rationally tailored properties. Soft- and reactive landing of ions onto solid or liquid surfaces introduces unprecedented selectivity into surface modification by completely eliminating the effect of solvent and sample contamination on the qualitymore » of the film. The ability to select the mass-to-charge ratio of the precursor ion, its kinetic energy and charge state along with precise control of the size, shape and position of the ion beam on the deposition target makes soft-landing an attractive approach for surface modification. High-purity uniform thin films on surfaces generated using mass-selected ion deposition facilitate understanding of critical interfacial phenomena relevant to catalysis, energy generation and storage, and materials science. Our efforts have been directed toward understanding charge retention by soft-landed metal and metal-oxide cluster ions, which may affect both their structure and reactivity. Specifically, we have examined the effect of the surface on charge retention by both positively and negatively charged cluster ions. We found that the electronic properties of the surface play an important role in charge retention by cluster cations. Meanwhile, the electron binding energy is a key factor determining charge retention by cluster anions. These findings provide the scientific foundation for the rational design of interfaces for advanced catalysts and energy storage devices. Further optimization of electrode-electrolyte interfaces for applications in energy storage and electrocatalysis may be achieved by understanding and controlling the properties of soft-landed cluster ions.« less

Update on inflammation in chronic kidney disease.

PubMed

Akchurin, Oleh M; Kaskel, Frederick

2015-01-01

Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting. The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials. Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in children). © 2015 S. Karger AG, Basel.

Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

PubMed

Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

2015-04-24

Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by adopting liquid chromatography tandem mass spectrometry. The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulate expression of specific cellulases and hemicellulases, and expression level as a function of substrate. Post translational modifications revealed deamidation of key cellulases including endoglucanases, cellobiohydrolases and glucosidases; and hemicellulases and lignin degrading enzymes. The knowledge on deamidated enzymes along with specific sites of modifications could be crucial information for further functional studies of these enzymes of A. fumigatus. Copyright © 2015 Elsevier B.V. All rights reserved.

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system.

PubMed

Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M; Görlach, Agnes

2017-06-01

Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post-translational histone modifications, ATP-dependent alterations to chromatin and non-coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage-specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. © 2017 The British Pharmacological Society.

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

PubMed Central

Kietzmann, Thomas; Petry, Andreas; Shvetsova, Antonina; Gerhold, Joachim M

2017-01-01

Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post‐translational histone modifications, ATP‐dependent alterations to chromatin and non‐coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage‐specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:28332701

Importance of tyrosine phosphorylation in receptor kinase complexes.

PubMed

Macho, Alberto P; Lozano-Durán, Rosa; Zipfel, Cyril

2015-05-01

Tyrosine phosphorylation is an important post-translational modification that is known to regulate receptor kinase (RK)-mediated signaling in animals. Plant RKs are annotated as serine/threonine kinases, but recent work has revealed that tyrosine phosphorylation is also crucial for the activation of RK-mediated signaling in plants. These initial observations have paved the way for subsequent detailed studies on the mechanism of activation of plant RKs and the biological relevance of tyrosine phosphorylation for plant growth and immunity. In this Opinion article we review recent reports on the contribution of RK tyrosine phosphorylation in plant growth and immunity; we propose that tyrosine phosphorylation plays a major regulatory role in the initiation and transduction of RK-mediated signaling in plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of ATM Protein Kinase Phosphorylation Sites by Mass Spectrometry.

PubMed

Graham, Mark E; Lavin, Martin F; Kozlov, Sergei V

2017-01-01

ATM (ataxia-telangiectasia mutated) protein kinase is a key regulator of cellular responses to DNA damage and oxidative stress. DNA damage triggers complex cascade of signaling events leading to numerous posttranslational modification on multitude of proteins. Understanding the regulation of ATM kinase is therefore critical not only for understanding the human genetic disorder ataxia-telangiectasia and potential treatment strategies, but essential for deciphering physiological responses of cells to stress. These responses play an important role in carcinogenesis, neurodegeneration, and aging. We focus here on the identification of DNA damage inducible ATM phosphorylation sites to understand the importance of autophosphorylation in the mechanism of ATM kinase activation. We demonstrate the utility of using immunoprecipitated ATM in quantitative LC-MS/MS workflow with stable isotope dimethyl labeling of ATM peptides for identification of phosphorylation sites.

LncRNA Structural Characteristics in Epigenetic Regulation

PubMed Central

Wang, Chenguang; Wang, Lianzong; Ding, Yu; Lu, Xiaoyan; Zhang, Guosi; Yang, Jiaxin; Zheng, Hewei; Wang, Hong; Jiang, Yongshuai; Xu, Liangde

2017-01-01

The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes. PMID:29292750

Application of epigenetic markers in molecular breeding of the swine.

PubMed

Zhang, Ke; Feng, Guang-de; Zhang, Bao-yun; Xiang, Wei; Chen, Long; Yang, Fang; Chu, Ming-xing; Wang, Ping-qing

2016-07-20

Livestock phenotypes are determined by the interaction of a variety of factors, including the genome, the epigenome and the environment. Epigenetics refers to gene expression changes without DNA sequence alterations. Epigenetic markers mainly include DNA methylation, histone modifications, non-coding RNAs, and imprinting genes. More and more researches show that epigenetic markers play an important role in the traits of pigs by modulating phenotype changes via gene expression. However, the role of epigenetic markers has caught little attention in swine breeding. The mechanism that influences important traits of swine has not been analyzed in detail, and it still lacks adequate scientific basis for practical applications. From the aspects of nutrition, diseases, important economic traits and trans-generational inheritance, we summarize the research, application prospects and challenges in the field of utilizing epigenetic markers in molecular breeding of pigs, thus providing a more comprehensive theoretical basis to promote more rapid research development in this field.

Evidence for glaciation in Elysium

NASA Technical Reports Server (NTRS)

Anderson, Duwayne M.

1987-01-01

Evidence for the existence of permafrost and the surface modification due to frost effects and the presence of ice on Mars dates from early observations. Later analysis of the Viking Orbiter imagery produced evidence suggesting the former presence of ice sheets that could have played a part in shaping the surface of Mars. Similarities were pointed out between a number of streamlined Martian channel features and similar streamlined landforms created by Antarctic ice sheet movement. A study of Viking Orbiter imagery of Granicus Valles and the surrounding terrain in Elysium has produced further evidence of glaciation on Mars. Volcanism has played an important role in developing the landscapes of the Elysium region. A possible explanation is that subsidence occurred during formation of the Martian moberg ridges due to the melting of ground ice near the eruption area while at a distance most of the ground ice in the permafrost is still present and the original elevation was preserved. Meltwater during and following eruptions might be suddenly released during subglacial volcanism into Granicus Valles in one case and into Hrad Valles in the other. Fluvial erosion thus could have played a role in shaping both.

Evolutionary changes of Hox genes and relevant regulatory factors provide novel insights into mammalian morphological modifications.

PubMed

Li, Kui; Sun, Xiaohui; Chen, Meixiu; Sun, Yingying; Tian, Ran; Wang, Zhengfei; Xu, Shixia; Yang, Guang

2018-01-01

The diversity of body plans of mammals accelerates the innovation of lifestyles and the extensive adaptation to different habitats, including terrestrial, aerial and aquatic habitats. However, the genetic basis of those phenotypic modifications, which have occurred during mammalian evolution, remains poorly explored. In the present study, we synthetically surveyed the evolutionary pattern of Hox clusters that played a powerful role in the morphogenesis along the head-tail axis of animal embryos and the main regulatory factors (Mll, Bmi1 and E2f6) that control the expression of Hox genes. A deflected density of repetitive elements and lineage-specific radical mutations of Mll have been determined in marine mammals with morphological changes, suggesting that evolutionary changes may alter Hox gene expression in these lineages, leading to the morphological modification of these lineages. Although no positive selection was detected at certain ancestor nodes of lineages, the increased ω values of Hox genes implied the relaxation of functional constraints of these genes during the mammalian evolutionary process. More importantly, 49 positively-selected sites were identified in mammalian lineages with phenotypic modifications, indicating adaptive evolution acting on Hox genes and regulatory factors. In addition, 3 parallel amino acid substitutions in some Hox genes were examined in marine mammals, which might be responsible for their streamlined body. © 2017 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

PubMed Central

Janczar, Szymon; Janczar, Karolina; Pastorczak, Agata; Harb, Hani; Paige, Adam J. W.; Zalewska-Szewczyk, Beata; Danilewicz, Marian; Mlynarski, Wojciech

2017-01-01

While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis. PMID:28054944

Tailored HIV-1 vectors for genetic modification of primary human dendritic cells and monocytes.

PubMed

Durand, Stéphanie; Nguyen, Xuan-Nhi; Turpin, Jocelyn; Cordeil, Stephanie; Nazaret, Nicolas; Croze, Séverine; Mahieux, Renaud; Lachuer, Joël; Legras-Lachuer, Catherine; Cimarelli, Andrea

2013-01-01

Monocyte-derived dendritic cells (MDDCs) play a key role in the regulation of the immune system and are the target of numerous gene therapy applications. The genetic modification of MDDCs is possible with human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LVs) but requires high viral doses to bypass their natural resistance to viral infection, and this in turn affects their physiological properties. To date, a single viral protein is able to counter this restrictive phenotype, Vpx, a protein derived from members of the HIV-2/simian immunodeficiency virus SM lineage that counters at least two restriction factors present in myeloid cells. By tagging Vpx with a short heterologous membrane-targeting domain, we have obtained HIV-1 LVs incorporating high levels of this protein (HIV-1-Src-Vpx). These vectors efficiently transduce differentiated MDDCs and monocytes either as previously purified populations or as populations within unsorted peripheral blood mononuclear cells (PBMCs). In addition, these vectors can be efficiently pseudotyped with receptor-specific envelopes, further restricting their cellular tropism almost uniquely to MDDCs. Compared to conventional HIV-1 LVs, these novel vectors allow for an efficient genetic modification of MDDCs and, more importantly, do not cause their maturation or affect their survival, which are unwanted side effects of the transduction process. This study describes HIV-1-Src-Vpx LVs as a novel potent tool for the genetic modification of differentiated MDDCs and of circulating monocyte precursors with strong potential for a wide range of gene therapy applications.

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

The concomitant effects of phrase length and informational content in sentence comprehension.

PubMed

Thornton, R; MacDonald, M C; Arnold, J E

2000-03-01

Recent evidence suggests that phrase length plays a crucial role in modification ambiguities. Using a self-paced reading task, we extended these results by examining the additional pragmatic effects that length manipulations may exert. The results demonstrate that length not only modulates modification preferences directly, but that it also necessarily changes the informational content of a sentence, which itself affects modification preferences. Our findings suggest that the same length manipulation affects multiple sources of constraints, both structural and pragmatic, which can each exert differing effects on processing.

Structural landscape of base pairs containing post-transcriptional modifications in RNA

PubMed Central

Seelam, Preethi P.; Sharma, Purshotam

2017-01-01

Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts toward understanding the structural and functional role of naturally occurring modified base pairs using a combination of X-ray crystal structure database analysis, sequence analysis, and advanced quantum chemical methods. Our bioinformatics analysis reveals that despite their presence in all major secondary structural elements, modified base pairs are most prevalent in tRNA crystal structures and most commonly involve guanine or uridine modifications. Further, analysis of tRNA sequences reveals additional examples of modified base pairs at structurally conserved tRNA regions and highlights the conservation patterns of these base pairs in three domains of life. Comparison of structures and binding energies of modified base pairs with their unmodified counterparts, using quantum chemical methods, allowed us to classify the base modifications in terms of the nature of their electronic structure effects on base-pairing. Analysis of specific structural contexts of modified base pairs in RNA crystal structures revealed several interesting scenarios, including those at the tRNA:rRNA interface, antibiotic-binding sites on the ribosome, and the three-way junctions within tRNA. These scenarios, when analyzed in the context of available experimental data, allowed us to correlate the occurrence and strength of modified base pairs with their specific functional roles. Overall, our study highlights the structural importance of modified base pairs in RNA and points toward the need for greater appreciation of the role of modified bases and their interactions, in the context of many biological processes involving RNA. PMID:28341704

Surface modifications of magnesium alloys for biomedical applications.

PubMed

Yang, Jingxin; Cui, Fuzhai; Lee, In Seop

2011-07-01

In recent years, research on magnesium (Mg) alloys had increased significantly for hard tissue replacement and stent application due to their outstanding advantages. Firstly, Mg alloys have mechanical properties similar to bone which avoid stress shielding. Secondly, they are biocompatible essential to the human metabolism as a factor for many enzymes. In addition, main degradation product Mg is an essential trace element for human enzymes. The most important reason is they are perfectly biodegradable in the body fluid. However, extremely high degradation rate, resulting in too rapid loss of mechanical strength in chloride containing environments limits their applications. Engineered artificial biomaterials with appropriate mechanical properties, surface chemistry, and surface topography are in a great demand. As the interaction between the cells and tissues with biomaterials at the tissue--implant interface is a surface phenomenon; surface properties play a major role in determining both the biological response to implants and the material response to the physiological condition. Therefore, the ability to modify the surface properties while preserve the bulk properties is important, and surface modification to form a hard, biocompatible and corrosion resistant modified layer have always been an interesting topic in biomaterials field. In this article, attempts are made to give an overview of the current research and development status of surface modification technologies of Mg alloys for biomedical materials research. Further, the advantages/disadvantages of the different methods and with regard to the most promising method for Mg alloys are discussed. Finally, the scientific challenges are proposed based on own research and the work of other scientists.

Biological Behavior of Osteoblast Cell and Apatite Forming Ability of the Surface Modified Ti Alloys.

PubMed

Zhao, Jingming; Hwang, K H; Choi, W S; Shin, S J; Lee, J K

2016-02-01

Titanium as one kind of biomaterials comes in direct contact with the body, making evaluation of biocompatibility an important aspect to biomaterials development. Surface chemistry of titanium plays an important role in osseointegration. Different surface modification alters the surface chemistry and result in different biological response. In this study, three kinds of mixed acid solutions were used to treat Ti specimens to induce Ca-P formation. Following a strong mixed acid activation process, Ca-P coating successfully formed on the Ti surfaces in simulated body fluid. Strong mixed acid increased the roughness of the metal surface, because the porous and rough surface allows better adhesion between Ca-P coatings and substrates. After modification of titanium surface by mixed acidic solution and subsequently H2O2/HCL treatment evaluation of biocompatibility was conducted from hydroxyapatite formation by biomimetic process and cell viability on modified titanium surface. Nano-scale modification of titanium surfaces can alter cellular and tissue responses, which may benefit osseointegration and dental implant therapy. Results from this study indicated that surface treatment methods affect the surface morphology, type of TiO2 layer formed and subsequent apatite deposition and biological responses. The thermo scientific alamarblue cell viability assay reagent is used to quantitatively measure the viability of mammalian cell lines, bacteria and fungi by incorporating a rapid, sensitive and reliable fluorometric/colorimetric growth indicator, without any toxic and side effect to cell line. In addition, mixed acid treatment uses a lower temperature and shorter time period than widely used alkali treatment.

Uncovering the Protein Lysine and Arginine Methylation Network in Arabidopsis Chloroplasts

PubMed Central

Mininno, Morgane; Brugière, Sabine; Gilgen, Annabelle; Ma, Sheng; Mazzoleni, Meryl; Gigarel, Océane; Martin-Laffon, Jacqueline; Ferro, Myriam; Ravanel, Stéphane

2014-01-01

Post-translational modification of proteins by the addition of methyl groups to the side chains of Lys and Arg residues is proposed to play important roles in many cellular processes. In plants, identification of non-histone methylproteins at a cellular or subcellular scale is still missing. To gain insights into the extent of this modification in chloroplasts we used a bioinformatics approach to identify protein methyltransferases targeted to plastids and set up a workflow to specifically identify Lys and Arg methylated proteins from proteomic data used to produce the Arabidopsis chloroplast proteome. With this approach we could identify 31 high-confidence Lys and Arg methylation sites from 23 chloroplastic proteins, of which only two were previously known to be methylated. These methylproteins are split between the stroma, thylakoids and envelope sub-compartments. They belong to essential metabolic processes, including photosynthesis, and to the chloroplast biogenesis and maintenance machinery (translation, protein import, division). Also, the in silico identification of nine protein methyltransferases that are known or predicted to be targeted to plastids provided a foundation to build the enzymes/substrates relationships that govern methylation in chloroplasts. Thereby, using in vitro methylation assays with chloroplast stroma as a source of methyltransferases we confirmed the methylation sites of two targets, plastid ribosomal protein L11 and the β-subunit of ATP synthase. Furthermore, a biochemical screening of recombinant chloroplastic protein Lys methyltransferases allowed us to identify the enzymes involved in the modification of these substrates. The present study provides a useful resource to build the methyltransferases/methylproteins network and to elucidate the role of protein methylation in chloroplast biology. PMID:24748391

In vitro electromagnetically stimulated SAOS-2 osteoblasts inside porous hydroxyapatite

PubMed Central

Fassina, Lorenzo; Saino, Enrica; Sbarra, Maria Sonia; Visai, Livia; De Angelis, Maria Gabriella Cusella; Magenes, Giovanni; Benazzo, Francesco

2009-01-01

One of the key challenges in reconstructive bone surgery is to provide living constructs that possess the ability to integrate in the surrounding tissue. Bone graft substitutes, such as autografts, allografts, xenografts, and biomaterials have been widely used to heal critical-size long bone defects due to trauma, tumor resection, congenital deformity, and tissue degeneration. In particular, porous hydroxyapatite is widely used in reconstructive bone surgery owing to its biocompatibility. In addition, the in vitro modification of hydroxyapatite with osteogenic signals enhances the tissue regeneration in vivo, suggesting that the biomaterial modification could play an important role in tissue engineering. In this study we have followed a biomimetic strategy where electromagnetically stimulated SAOS-2 human osteoblasts proliferated and built their extracellular matrix inside a porous hydroxyapatite scaffold. The electromagnetic stimulus had the following parameters: intensity of the magnetic field equal to 2 mT, amplitude of the induced electric tension equal to 5 mV, frequency of 75 Hz, and pulse duration of 1.3 ms. In comparison with control conditions, the electromagnetic stimulus increased the cell proliferation and the surface coating with bone proteins (decorin, osteocalcin, osteopontin, type-I collagen, and type-III collagen). The physical stimulus aimed at obtaining a better modification of the biomaterial internal surface in terms of cell colonization and coating with bone matrix. PMID:19827111

Attentional bias modification training for insomnia: A double-blind placebo controlled randomized trial

PubMed Central

Lancee, Jaap; Yasiney, Samya L.; Brendel, Ruben S.; Boffo, Marilisa; Clarke, Patrick J. F.; Salemink, Elske

2017-01-01

Background Attentional bias toward sleep-related information is believed to play a key role in insomnia. If attentional bias is indeed of importance, changing this bias should then in turn have effects on insomnia complaints. In this double-blind placebo controlled randomized trial we investigated the efficacy of attentional bias modification training in the treatment of insomnia. Method We administered baseline, post-test, and one-week follow-up measurements of insomnia severity, sleep-related worry, depression, and anxiety. Participants meeting DSM-5 criteria for insomnia were randomized into an attentional bias training group (n = 67) or a placebo training group (n = 70). Both groups received eight training sessions over the course of two weeks. All participants kept a sleep diary for four consecutive weeks (one week before until one week after the training sessions). Results There was no additional benefit for the attentional bias training over the placebo training on sleep-related indices/outcome measures. Conclusions The absence of the effect may be explained by the fact that there was neither attentional bias at baseline nor any reduction in the bias after the training. Either way, this study gives no support for attentional bias modification training as a stand-alone intervention for ameliorating insomnia complaints. PMID:28423038

Mitochondria are an early target of oxidative modifications in senescing legume nodules.

PubMed

Matamoros, Manuel A; Fernández-García, Nieves; Wienkoop, Stefanie; Loscos, Jorge; Saiz, Ana; Becana, Manuel

2013-02-01

Legume nodule senescence is a poorly understood process involving a decrease in N(2) fixation and an increase in proteolytic activity. Some physiological changes during nodule aging have been reported, but scarce information is available at the subcellular level. Biochemical, immunological and proteomic approaches were used to provide insight into the effects of aging on the mitochondria and cytosol of nodule host cells. In the mitochondria, the oxidative modification of lipids and proteins was associated with a marked decline in glutathione, a reduced capacity to regenerate ascorbate, and upregulation of alternative oxidase and manganese superoxide dismutase. In the cytosol, there were consistent reductions in the protein concentrations of carbon metabolism enzymes, inhibition of protein synthesis and increase in serine proteinase activity, disorganization of cytoskeleton, and a sharp reduction of cytosolic proteins, but no detectable accumulation of oxidized molecules. We conclude that nodule mitochondria are an early target of oxidative modifications and a likely source of redox signals. Alternative oxidase and manganese superoxide dismutase may play important roles in controlling ROS concentrations and the redox state of mitochondria. The finding that specific methionine residues of a cytosolic glutamine synthetase isoform are sulfoxidized suggests a regulatory role of this enzyme in senescing nodules. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Redox proteomics of tomato in response to Pseudomonas syringae infection

PubMed Central

Balmant, Kelly Mayrink; Parker, Jennifer; Yoo, Mi-Jeong; Zhu, Ning; Dufresne, Craig; Chen, Sixue

2015-01-01

Unlike mammals with adaptive immunity, plants rely on their innate immunity based on pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) for pathogen defense. Reactive oxygen species, known to play crucial roles in PTI and ETI, can perturb cellular redox homeostasis and lead to changes of redox-sensitive proteins through modification of cysteine sulfhydryl groups. Although redox regulation of protein functions has emerged as an important mechanism in several biological processes, little is known about redox proteins and how they function in PTI and ETI. In this study, cysTMT proteomics technology was used to identify similarities and differences of protein redox modifications in tomato resistant (PtoR) and susceptible (prf3) genotypes in response to Pseudomonas syringae pv tomato (Pst) infection. In addition, the results of the redox changes were compared and corrected with the protein level changes. A total of 90 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism, biosynthesis of cysteine, sucrose and brassinosteroid, cell wall biogenesis, polysaccharide/starch biosynthesis, cuticle development, lipid metabolism, proteolysis, tricarboxylic acid cycle, protein targeting to vacuole, and oxidation–reduction. This inventory of previously unknown protein redox switches in tomato pathogen defense lays a foundation for future research toward understanding the biological significance of protein redox modifications in plant defense responses. PMID:26504582

Histones and their modifications in ovarian cancer - drivers of disease and therapeutic targets.

PubMed

Marsh, Deborah J; Shah, Jaynish S; Cole, Alexander J

2014-01-01

Epithelial ovarian cancer has the highest mortality of the gynecological malignancies. High grade serous epithelial ovarian cancer (SEOC) is the most common subtype, with the majority of women presenting with advanced disease where 5-year survival is around 25%. Platinum-based chemotherapy in combination with paclitaxel remains the most effective treatment despite platinum therapies being introduced almost 40 years ago. Advances in molecular medicine are underpinning new strategies for the treatment of cancer. Major advances have been made by international initiatives to sequence cancer genomes. For SEOC, with the exception of TP53 that is mutated in virtually 100% of these tumors, there is no other gene mutated at high frequency. There is extensive copy number variation, as well as changes in methylation patterns that will influence gene expression. To date, the role of histones and their post-translational modifications in ovarian cancer is a relatively understudied field. Post-translational histone modifications play major roles in gene expression as they direct the configuration of chromatin and so access by transcription factors. Histone modifications include methylation, acetylation, and monoubiquitination, with involvement of enzymes including histone methyltransferases, histone acetyltransferases/deacetylases, and ubiquitin ligases/deubiquitinases, respectively. Complexes such as the Polycomb repressive complex also play roles in the control of histone modifications and more recently roles for long non-coding RNA and microRNAs are emerging. Epigenomic-based therapies targeting histone modifications are being developed and offer new approaches for the treatment of ovarian cancer. Here, we discuss histone modifications and their aberrant regulation in malignancy and specifically in ovarian cancer. We review current and upcoming histone-based therapies that have the potential to inform and improve treatment strategies for women with ovarian cancer.

Update: Mechanisms underlying N6-methyladenosine modification of eukaryotic mRNA

PubMed Central

Wang, Yang; Zhao, Jing Crystal

2016-01-01

Summary Eukaryotic messenger RNA (mRNA) undergoes chemical modification both at the 5′cap [1, 2] and internally [3–14]. Among internal modifications, m6A, by far the most abundant, is present in all eukaryotes examined, including mammals [3–6], flies [15], plants [16, 17] and yeast [18, 19]. m6A modification plays an essential role in diverse biological processes. Over the past few years, our knowledge relevant to establishment and function of this modification has grown rapidly. This review focuses on technologies that have facilitated m6A detection in mRNAs, identification of m6A methylation enzymes and binding proteins, and potential functions of the modification at the molecular level. Regarding m6A function at cellular or organismal levels or in disease, please refer to other recent reviews [20–23]. PMID:27793360

O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis.

PubMed

Tardio, L; Andrés-Bergós, J; Zachara, N E; Larrañaga-Vera, A; Rodriguez-Villar, C; Herrero-Beaumont, G; Largo, R

2014-02-01

There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1α. Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis. Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

PubMed Central

Kinnunen, Tarja K.

2014-01-01

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease. PMID:25054285

Development and integration of a scalable low NOx combustion chamber for a hydrogen-fueled aerogas turbine

NASA Astrophysics Data System (ADS)

Boerner, S.; Funke, H. H.-W.; Hendrick, P.; Recker, E.; Elsing, R.

2013-03-01

The usage of alternative fuels in aircraft industry plays an important role of current aero engine research and development processes. The micromix burning principle allows a secure and low NOx combustion of gaseous hydrogen. The combustion principle is based on the fluid phenomenon of jet in cross flow and achieves a significant lowering in NOx formation by using multiple miniaturized flames. The paper highlights the development and the integration of a combustion chamber, based on the micromix combustion principle, into an Auxiliary Power Unit (APU) GTCP 36-300 with regard to the necessary modifications on the gas turbine and on the engine controller.

Dynamic rheological properties of dough as affected by amylases from various sources.

PubMed

Doğan, Ismail S

2002-12-01

The effect of alpha-amylases from cereal, fungal, and bacterial sources on dough dynamic rheological properties was investigated. Dynamic rheological study of flour-and-water doughs during resting period showed significant changes in dough rheological properties as a function of alpha-amylases. Addition of alpha-amylases caused a time-dependent decrease in G', storage modulus. The enzyme action on starch during baking increased viscous flow properties. These changes were temperature-dependent. The thermal inactivation temperature of alpha-amylase plays an important role in modification of starch. Rheological changes in dough will alter the machinability of the dough and the quality of end products.

Use of Atmospheric-Pressure Plasma Jet for Polymer Surface Modification: An Overview

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

Kuettner, Lindsey A.

Atmospheric-pressure plasma jets (APPJs) are playing an increasingly important role in materials processing procedures. Plasma treatment is a useful tool to modify surface properties of materials, especially polymers. Plasma reacts with polymer surfaces in numerous ways thus the type of process gas and plasma conditions must be explored for chosen substrates and materials to maximize desired properties. This report discusses plasma treatments and looks further into atmospheric-pressure plasma jets and the effects of gases and plasma conditions. Following the short literature review, a general overview of the future work and research at Los Alamos National Laboratory (LANL) is discussed.

Significance of a Posttranslational Modification of the PilA Protein of Geobacter sulfurreducens for Surface Attachment, Biofilm Formation, and Growth on Insoluble Extracellular Electron Acceptors.

PubMed

Richter, Lubna V; Franks, Ashley E; Weis, Robert M; Sandler, Steven J

2017-04-15

Geobacter sulfurreducens , an anaerobic metal-reducing bacterium, possesses type IV pili. These pili are intrinsic structural elements in biofilm formation and, together with a number of c -type cytochromes, are thought to serve as conductive nanowires enabling long-range electron transfer (ET) to metal oxides and graphite anodes. Here, we report that a posttranslational modification of a nonconserved amino acid residue within the PilA protein, the structural subunit of the type IV pili, is crucial for growth on insoluble extracellular electron acceptors. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the secreted PilA protein revealed a posttranslational modification of tyrosine-32 with a moiety of a mass consistent with a glycerophosphate group. Mutating this tyrosine into a phenylalanine inhibited cell growth with Fe(III) oxides as the sole electron acceptor. In addition, this amino acid substitution severely diminished biofilm formation on graphite surfaces and impaired current output in microbial fuel cells. These results demonstrate that the capability to attach to insoluble electron acceptors plays a crucial role for the cells' ability to utilize them. The work suggests that glycerophosphate modification of Y32 is a key factor contributing to the surface charge of type IV pili, influencing the adhesion of Geobacter to specific surfaces. IMPORTANCE Type IV pili are bacterial appendages that function in cell adhesion, virulence, twitching motility, and long-range electron transfer (ET) from bacterial cells to insoluble extracellular electron acceptors. The mechanism and role of type IV pili for ET in Geobacter sulfurreducens is still a subject of research. In this study, we identified a posttranslational modification of the major G. sulfurreducens type IV pilin, suggested to be a glycerophosphate moiety. We show that a mutant in which the glycerophosphate-modified tyrosine-32 is replaced with a phenylalanine has reduced abilities for ET and biofilm formation compared with those of the wild type. The results show the importance of the glycerophosphate-modified tyrosine for surface attachment and electron transfer in electrode- or Fe(III)-respiring G. sulfurreducens cells. Copyright © 2017 American Society for Microbiology.

Significance of a Posttranslational Modification of the PilA Protein of Geobacter sulfurreducens for Surface Attachment, Biofilm Formation, and Growth on Insoluble Extracellular Electron Acceptors

PubMed Central

Franks, Ashley E.; Weis, Robert M.; Sandler, Steven J.

2017-01-01

ABSTRACT Geobacter sulfurreducens, an anaerobic metal-reducing bacterium, possesses type IV pili. These pili are intrinsic structural elements in biofilm formation and, together with a number of c-type cytochromes, are thought to serve as conductive nanowires enabling long-range electron transfer (ET) to metal oxides and graphite anodes. Here, we report that a posttranslational modification of a nonconserved amino acid residue within the PilA protein, the structural subunit of the type IV pili, is crucial for growth on insoluble extracellular electron acceptors. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the secreted PilA protein revealed a posttranslational modification of tyrosine-32 with a moiety of a mass consistent with a glycerophosphate group. Mutating this tyrosine into a phenylalanine inhibited cell growth with Fe(III) oxides as the sole electron acceptor. In addition, this amino acid substitution severely diminished biofilm formation on graphite surfaces and impaired current output in microbial fuel cells. These results demonstrate that the capability to attach to insoluble electron acceptors plays a crucial role for the cells' ability to utilize them. The work suggests that glycerophosphate modification of Y32 is a key factor contributing to the surface charge of type IV pili, influencing the adhesion of Geobacter to specific surfaces. IMPORTANCE Type IV pili are bacterial appendages that function in cell adhesion, virulence, twitching motility, and long-range electron transfer (ET) from bacterial cells to insoluble extracellular electron acceptors. The mechanism and role of type IV pili for ET in Geobacter sulfurreducens is still a subject of research. In this study, we identified a posttranslational modification of the major G. sulfurreducens type IV pilin, suggested to be a glycerophosphate moiety. We show that a mutant in which the glycerophosphate-modified tyrosine-32 is replaced with a phenylalanine has reduced abilities for ET and biofilm formation compared with those of the wild type. The results show the importance of the glycerophosphate-modified tyrosine for surface attachment and electron transfer in electrode- or Fe(III)-respiring G. sulfurreducens cells. PMID:28138101

Elucidation of Enzymatic Mechanism of Phenazine Biosynthetic Protein PhzF Using QM/MM and MD Simulations

PubMed Central

Liu, Fei; Zhao, Yi-Lei; Wang, Xiaolei; Hu, Hongbo; Peng, Huasong; Wang, Wei; Wang, Jing-Fang; Zhang, Xuehong

2015-01-01

The phenazine biosynthetic pathway is of considerable importance for the pharmaceutical industry. The pathway produces two products: phenazine-1,6-dicarboxylic acid and phenazine-1-carboxylic acid. PhzF is an isomerase that catalyzes trans-2,3-dihydro-3-hydroxyanthranilic acid isomerization and plays an essential role in the phenazine biosynthetic pathway. Although the PhzF crystal structure has been determined recently, an understanding of the detailed catalytic mechanism and the roles of key catalytic residues are still lacking. In this study, a computational strategy using a combination of molecular modeling, molecular dynamics simulations, and quantum mechanics/molecular mechanics simulations was used to elucidate these important issues. The Apo enzyme, enzyme–substrate complexes with negatively charged Glu45, enzyme–transition state analog inhibitor complexes with neutral Glu45, and enzyme–product complexes with negatively charged Glu45 structures were optimized and modeled using a 200 ns molecular dynamics simulation. Residues such as Gly73, His74, Asp208, Gly212, Ser213, and water, which play important roles in ligand binding and the isomerization reaction, were comprehensively investigated. Our results suggest that the Glu45 residue at the active site of PhzF acts as a general base/acid catalyst during proton transfer. This study provides new insights into the detailed catalytic mechanism of PhzF and the results have important implications for PhzF modification. PMID:26414009

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

Prey Range and Genome Evolution of Halobacteriovorax marinus Predatory Bacteria from an Estuary

PubMed Central

Enos, Brett G.; Anthony, Molly K.; DeGiorgis, Joseph A.

2018-01-01

ABSTRACT Halobacteriovorax strains are saltwater-adapted predatory bacteria that attack Gram-negative bacteria and may play an important role in shaping microbial communities. To understand how Halobacteriovorax strains impact ecosystems and develop them as biocontrol agents, it is important to characterize variation in predation phenotypes and investigate Halobacteriovorax genome evolution. We isolated Halobacteriovorax marinus BE01 from an estuary in Rhode Island using Vibrio from the same site as prey. Small, fast-moving, attack-phase BE01 cells attach to and invade prey cells, consistent with the intraperiplasmic predation strategy of the H. marinus type strain, SJ. BE01 is a prey generalist, forming plaques on Vibrio strains from the estuary, Pseudomonas from soil, and Escherichia coli. Genome analysis revealed extremely high conservation of gene order and amino acid sequences between BE01 and SJ, suggesting strong selective pressure to maintain the genome in this H. marinus lineage. Despite this, we identified two regions of gene content difference that likely resulted from horizontal gene transfer. Analysis of modal codon usage frequencies supports the hypothesis that these regions were acquired from bacteria with different codon usage biases than H. marinus. In one of these regions, BE01 and SJ carry different genes associated with mobile genetic elements. Acquired functions in BE01 include the dnd operon, which encodes a pathway for DNA modification, and a suite of genes involved in membrane synthesis and regulation of gene expression that was likely acquired from another Halobacteriovorax lineage. This analysis provides further evidence that horizontal gene transfer plays an important role in genome evolution in predatory bacteria. IMPORTANCE Predatory bacteria attack and digest other bacteria and therefore may play a role in shaping microbial communities. To investigate phenotypic and genotypic variation in saltwater-adapted predatory bacteria, we isolated Halobacteriovorax marinus BE01 from an estuary in Rhode Island, assayed whether it could attack different prey bacteria, and sequenced and analyzed its genome. We found that BE01 is a prey generalist, attacking bacteria from different phylogenetic groups and environments. Gene order and amino acid sequences are highly conserved between BE01 and the H. marinus type strain, SJ. By comparative genomics, we detected two regions of gene content difference that likely occurred via horizontal gene transfer events. Acquired genes encode functions such as modification of DNA, membrane synthesis and regulation of gene expression. Understanding genome evolution and variation in predation phenotypes among predatory bacteria will inform their development as biocontrol agents and clarify how they impact microbial communities. PMID:29359184

The relationship between water loss, mechanical stress, and molecular structure of human stratum corneum ex vivo.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Biniek, Krysta; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Dauskardt, Reinhold; Baillet-Guffroy, Arlette

2015-03-01

Proper hydration of the stratum corneum (SC) is important for maintaining skin's vital functions. Water loss causes development of drying stresses, which can be perceived as 'tightness', and plays an important role in dry skin damage processes. However, molecular structure modifications arising from water loss and the subsequent development of stress has not been established. We investigated the drying stress mechanism by studying, ex vivo, the behaviors of the SC components during water desorption from initially fully hydrated samples using Raman spectroscopy. Simultaneously, we measure the SC mechanical stress with a substrate curvature instrument. Very good correlations of water loss to the mechanical stress of the stratum corneum were obtained, and the latter was found to depend mainly on the unbound water fraction. In addition to that, the water loss is accompanied with an increase of lipids matrix compactness characterized by lower chain freedom, while protein structure showed an increase in amount of α-helices, a decline in α-sheets, and an increase in folding in the tertiary structure of keratin. The drying process of SC involves a complex interplay of water binding, molecular modifications, and mechanical stress. This article provides a better understanding of the molecular mechanism associated to SC mechanics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation

PubMed Central

Leus, Niek G.J.; Zwinderman, Martijn R.H.; Dekker, Frank J.

2016-01-01

Activation of inflammatory gene expression is regulated, among other factors, by post-translational modifications of histone proteins. The most investigated type of histone modifications are lysine acetylations. Histone deacetylases (HDACs) remove acetylations from lysines, thereby influencing (inflammatory) gene expression. Intriguingly, apart from histones, HDACs also target non-histone proteins. The nuclear factor κB (NF-κB) pathway is an important regulator in the expression of numerous inflammatory genes, and acetylation plays a crucial role in regulating its responses. Several studies have shed more light on the role of HDAC 1-3 in inflammation with a particular pro-inflammatory role for HDAC 3. Nevertheless, the HDAC-NF-κB interactions in inflammatory signalling have not been fully understood. An important challenge in targeting the regulatory role of HDACs in the NF-κB pathway is the development of highly potent small molecules that selectively target HDAC iso-enzymes. This review focuses on the role of HDAC 3 in (NF-κB-mediated) inflammation and NF-κB lysine acetylation. In addition, we address the application of frequently used small molecule HDAC inhibitors as an approach to attenuate inflammatory responses, and their potential as novel therapeutics. Finally, recent progress and future directions in medicinal chemistry efforts aimed at HDAC 3-selective inhibitors are discussed. PMID:27371876

Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior.

PubMed

Matsuda, Ken Ichi; Mori, Hiroko; Nugent, Bridget M; Pfaff, Donald W; McCarthy, Margaret M; Kawata, Mitsuhiro

2011-07-01

Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in masculinization of the brain (estrogen receptor α and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide directed against the mRNA for HDAC2 and -4 in newborn male rats. Aspects of male sexual behavior in adulthood were significantly reduced by administration of either trichostatin A or antisense oligodeoxynucleotide. These results demonstrate that HDAC activity during the early postnatal period plays a crucial role in the masculinization of the brain via modifications of histone acetylation status.

Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response

PubMed Central

Zan, Hong; Casali, Paolo

2015-01-01

Epigenetic modifications, such as histone post-translational modifications, DNA methylation, and alteration of gene expression by non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are heritable changes that are independent from the genomic DNA sequence. These regulate gene activities and, therefore, cellular functions. Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. Such alterations instruct B cells to undergo immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM), as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1. These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. Combinatorial histone modifications also function as histone codes to target CSR and, possibly, SHM machinery to the Ig loci by recruiting specific adaptors that can stabilize CSR/SHM factors. In addition, lncRNAs, such as recently reported lncRNA-CSR and an lncRNA generated through transcription of the S region that form G-quadruplex structures, are also important for CSR targeting. Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens, such as those on microbial pathogens, and generation of pathogenic autoantibodies, IgE in allergic reactions, as well as B cell neoplasia. Epigenetic marks would be attractive targets for new therapeutics for autoimmune and allergic diseases, and B cell malignancies. PMID:26697022

Surface Modifications and Their Effects on Titanium Dental Implants

PubMed Central

Jemat, A.; Ghazali, M. J.; Razali, M.; Otsuka, Y.

2015-01-01

This review covers several basic methodologies of surface treatment and their effects on titanium (Ti) implants. The importance of each treatment and its effects will be discussed in detail in order to compare their effectiveness in promoting osseointegration. Published literature for the last 18 years was selected with the use of keywords like titanium dental implant, surface roughness, coating, and osseointegration. Significant surface roughness played an important role in providing effective surface for bone implant contact, cell proliferation, and removal torque, despite having good mechanical properties. Overall, published studies indicated that an acid etched surface-modified and a coating application on commercial pure titanium implant was most preferable in producing the good surface roughness. Thus, a combination of a good surface roughness and mechanical properties of titanium could lead to successful dental implants. PMID:26436097

Application of Canonical Effective Methods to Background-Independent Theories

NASA Astrophysics Data System (ADS)

Buyukcam, Umut

Effective formalisms play an important role in analyzing phenomena above some given length scale when complete theories are not accessible. In diverse exotic but physically important cases, the usual path-integral techniques used in a standard Quantum Field Theory approach seldom serve as adequate tools. This thesis exposes a new effective method for quantum systems, called the Canonical Effective Method, which owns particularly wide applicability in backgroundindependent theories as in the case of gravitational phenomena. The central purpose of this work is to employ these techniques to obtain semi-classical dynamics from canonical quantum gravity theories. Application to non-associative quantum mechanics is developed and testable results are obtained. Types of non-associative algebras relevant for magnetic-monopole systems are discussed. Possible modifications of hypersurface deformation algebra and the emergence of effective space-times are presented. iii.

New Therapeutic Drugs from Bioactive Natural Molecules: the Role of Gut Microbiota Metabolism in Neurodegenerative Diseases.

PubMed

Di Meo, Francesco; Donato, Stella; Di Pardo, Alba; Maglione, Vittorio; Filosa, Stefania; Crispi, Stefania

2018-04-03

The gut-brain axis is considered a neuroendocrine system, which connects brain and gastrointestinal tract and plays an important role in stress response. The homeostasis of gut-brain axis is important for healthy conditions and its alterations are associated to neurological disorders and neurodegenerative diseases. Gut microbiota is a dynamic ecosystem that can be altered by external factors such as diet composition, antibiotics or xenobiotics. Recent advances in gut microbiota analyses indicate that the gut bacterial community plays a key role in maintaining normal brain functions. Recent metagenomic analyses have elucidated that the relationship between gut and brain, either in normal or in pathological conditions, reflects the existence of a "microbiota-gut-brain" axis. Gut microbiota composition can be influenced by dietary ingestion of probiotics or natural bioactive molecules such as prebiotics and polyphenols. Their derivatives coming from microbiota metabolism can affect both gut bacterial composition and brain biochemistry. Modifications of microbiota composition by natural bioactive molecules could be used to restore the altered brain functions, which characterize neurodegenerative diseases, leading to consider these compounds as novel therapeutic strategies for the treatment of neuropathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Relationship Between Early Maladaptive Schemas, Depression, and Generalized Anxiety among Adults Seeking Residential Treatment for Substance Use Disorders.

PubMed

Shorey, Ryan C; Elmquist, Joanna; Anderson, Scott; Stuart, Gregory L

2015-01-01

Previous research has shown that early maladaptive schemas (EMS) play an important role in substance use, depression, and anxiety. However, few studies have examined the role of EMS within the context of all three concurrently. The goal of this study was to determine the role of EMS in predicting symptoms of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) among adults in residential treatment for substance dependence. We used pre-existing patient records of adults diagnosed with a substance use disorder from a residential substance use treatment facility (N=122). The EMS domains of disconnection and rejection and impaired limits were associated with symptoms of MDD and the domain of impaired autonomy and performance was associated with symptoms of GAD, even after controlling for age, gender, years of education, alcohol use, drug use, and symptoms of MDD (when predicting GAD) and GAD (when predicting MDD). Findings suggest that EMS may play an important role in comorbid mental health problems among men and women in residential substance use treatment. Continued treatment outcome research is needed to examine whether modification of EMS results in improved mental health and substance use outcomes.

You are what you eat: O-linked N-acetylglucosamine in disease, development and epigenetics.

PubMed

Olivier-Van Stichelen, Stéphanie; Hanover, John A

2015-07-01

The O-linked N-acetylglucosamine (O-GlcNAc) modification is both responsive to nutrient availability and capable of altering intracellular cellular signalling. We summarize data defining a role for O-GlcNAcylation in metabolic homeostasis and epigenetic regulation of development in the intrauterine environment. O-GlcNAc transferase (OGT) catalyzes nutrient-driven O-GlcNAc addition and is subject to random X-inactivation. OGT plays key roles in growth factor signalling, stem cell biology, epigenetics and possibly imprinting. The O-GlcNAcase, which removes O-GlcNAc, is subject to tight regulation by higher order chromatin structure. O-GlcNAc cycling plays an important role in the intrauterine environment wherein OGT expression is an important biomarker of placental stress. Regulation of O-GlcNAc cycling by X-inactivation, epigenetic regulation and nutrient-driven processes makes it an ideal candidate for a nutrient-dependent epigenetic regulator of human disease. In addition, O-GlcNAc cycling influences chromatin modifiers critical to the regulation and timing of normal development including the polycomb repression complex and the ten-eleven translocation proteins mediating DNA methyl cytosine demethylation. The pathway also impacts the hypothalamic-pituitary-adrenal axis critical to intrauterine programming influencing disease susceptibility in later life.

Discovery of a novel protein modification: alpha-glycerophosphate is a substituent of meningococcal pilin.

PubMed Central

Stimson, E; Virji, M; Barker, S; Panico, M; Blench, I; Saunders, J; Payne, G; Moxon, E R; Dell, A; Morris, H R

1996-01-01

Pili, which are filamentous protein structures on the surface of the meningitis-causing organism Neisseria meningitidis, are known to be post-translationally modified with substituents that affect their mobility in SDS/PAGE and which might play a crucial role in adherence and bloodstream invasion. Tryptic digests of pili were analysed by fast atom bombardment and electrospray MS to identify putative modifications. Serine-93 was found to carry a novel modification of alpha-glycerophosphate. This is the first time that alpha-glycerophosphate has been observed as a substituent of a prokaryotic or eukaryotic protein. PMID:8645220

Development of Multiple Cell-Based Assays for the Detection of Histone H3 Lys27 Trimethylation (H3K27me3)

PubMed Central

Lu, Lihui; Wu, Jianghong

2013-01-01

Abstract Posttranslational modification of histone proteins in eukaryotes plays an important role in gene transcription and chromatin structure. Dysregulation of the enzymes involved in histone modification has been linked to many cancer forms, making this target class a potential new area for therapeutics. A reliable assay to monitor small-molecule inhibition of various epigenetic enzymes should play a critical role in drug discovery to fight cancer. However, it has been challenging to develop cell-based assays for high-throughput screening (HTS) and compound profiling. Recently, two homogeneous cell-based assay kits using the AlphaLISA® and LanthaScreen® technologies to detect trimethyl histone H3 Lysine 27 have become commercially available, and a heterogeneous cell assay with modified dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA®) format has been reported. To compare their pros and cons, we evaluated, optimized, and validated these three assay formats in three different cell lines and compared their activities with traditional Western blot detection of histone methylation inhibition by using commercial and in-house small-molecule inhibitors. Our data indicate that, although all four formats produced acceptable results, the homogeneous AlphaLISA assay was best suited for HTS and compound profiling due to its wider window and ease of automation. The DELFIA and Western blot assays were useful as validation tools to confirm the cell activities and eliminate potential false-positive compounds. PMID:23992119

Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis.

PubMed

Carrozzo, Rosalba; Rizza, Teresa; Stringaro, Annarita; Pierini, Roberta; Mormone, Elisabetta; Santorelli, Filippo M; Malorni, Walter; Matarrese, Paola

2004-07-01

The key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally-inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK(-) osteosarcoma cell line deprived from its own mtDNA in order to insert mutated mtDNAs. Analysis of mitochondrial features in these cybrids indicated that both mitochondrial DNA mutations produced evidence of biochemical, functional and ultrastructural modifications of mitochondria, and that these modifications were associated with an increased apoptotic proneness. Cybrids were highly susceptible to two different apoptotic stimuli, tumour necrosis factor-alpha and Staurosporin. The mechanism involved was the mitochondrial 'intrinsic' pathway, i.e. the caspase 9-driven cascade. More importantly, our results also indicated that the polarization state of the mitochondrial membrane, i.e. a constitutive hyperpolarization detected in cybrid clones, played a specific role. Interestingly, the different effects of the two mutations in terms of susceptibility to apoptosis probably reflect the deeper bioenergetic defect associated with the L217R mutation. This work provides the first evidence that hyperpolarization of mitochondria may be a 'risk factor' for cells with a deep ATPase dysfunction, such as cells from patients with maternally-inherited Leigh syndrome.

Kaposi's Sarcoma-Associated Herpesvirus Utilizes and Manipulates RNA N6-Adenosine Methylation To Promote Lytic Replication

PubMed Central

Chen, E. Ricky; Nilsen, Timothy W.

2017-01-01

ABSTRACT N6-adenosine methylation (m6A) is the most common posttranscriptional RNA modification in mammalian cells. We found that most transcripts encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome undergo m6A modification. The levels of m6A-modified mRNAs increased substantially upon stimulation for lytic replication. The blockage of m6A inhibited splicing of the pre-mRNA encoding the replication transcription activator (RTA), a key KSHV lytic switch protein, and halted viral lytic replication. We identified several m6A sites in RTA pre-mRNA crucial for splicing through interactions with YTH domain containing 1 (YTHDC1), an m6A nuclear reader protein, in conjunction with serine/arginine-rich splicing factor 3 (SRSF3) and SRSF10. Interestingly, RTA induced m6A and enhanced its own pre-mRNA splicing. Our results not only demonstrate an essential role of m6A in regulating RTA pre-mRNA splicing but also suggest that KSHV has evolved a mechanism to manipulate the host m6A machinery to its advantage in promoting lytic replication. IMPORTANCE KSHV productive lytic replication plays a pivotal role in the initiation and progression of Kaposi's sarcoma tumors. Previous studies suggested that the KSHV switch from latency to lytic replication is primarily controlled at the chromatin level through histone and DNA modifications. The present work reports for the first time that KSHV genome-encoded mRNAs undergo m6A modification, which represents a new mechanism at the posttranscriptional level in the control of viral replication. PMID:28592530

Studies on chemical modification of cold agglutinin from the snail Achatina fulica.

PubMed Central

Sarkar, M; Mitra, D; Sen, A K

1987-01-01

The cold agglutinin isolated from the albumin gland of the snail Achatina fulica was modified with various chemical reagents in order to detect the amino acids and/or carbohydrate residues present in its carbohydrate-binding sites. Treatment with reagents considered specific for modification of lysine, arginine and tryptophan residues of the cold agglutinin did not affect the carbohydrate-binding activity of the agglutinin. Modification of tyrosine residues showed some change. However, modification with carbodiimide followed by alpha-aminobutyric acid methyl ester causes almost complete loss of its binding activity, indicating the involvement of aspartic acid and glutamic acid in its carbohydrate-binding activity. The carbohydrate residues of the cold agglutinin were removed by beta-elimination reaction, indicating that the sugars are O-glycosidically linked to protein part of the molecule. Removal of galactose residues from the cold agglutinin by the action of beta-galactosidase indicated that the galactose molecules are beta-linked. These carbohydrate-modified glycoproteins showed a marked change in agglutination property, i.e. they agglutinated rabbit erythrocytes at both 10 degrees C and 25 degrees C, indicating that the galactose residues of the glycoprotein play an important role in the cold-agglutination property of the glycoprotein. The c.d. data showed the presence of an almost identical type of random-coil conformation in the native cold agglutinin at 10 degrees C and in the carbohydrate-modified glycoprotein at 10 degrees C and 25 degrees C. This particular random-coil conformation is essential for carbohydrate-binding property of the agglutinin. Images Fig. 1. PMID:3118867

Mechanisms of Enhanced Hemoglobin Electroactivity on Carbon Electrodes upon Exposure to a Water-Miscible Primary Alcohol.

PubMed

Tom, Justin; Jakubec, Philip J; Andreas, Heather A

2018-05-01

Exposing a carbon electrode to hemoglobin (Hb) and alcoholic solvents, such as methanol, ethanol or 1-propanol, drastically changes Hb electroactivity, but until this work, the important underlying mechanisms were unclear. For the first time, we show that these alcohols impact Hb electroactivity via three mechanisms: modification of the carbon surface oxides on the glassy carbon (GC) electrode, Hb film formation, and structural changes to Hb. C 1s X-ray photoelectron spectroscopy provided evidence for significant alcohol-induced modification of the carbon surface oxides, and differential pulse voltammetry showed links between these modifications and Hb electroactivity. Spectroscopic ellipsometry showed that Hb films formed during exposure to Hb- and alcohol-containing electrolytes increased in thickness with increasing alcohol content, although film thickness played only a minor role in Hb electroactivity. Alcohol-induced structural changes in Hb are confirmed with UV-visible absorption and fluorescence data, showing that Hb denaturation also was a significant factor in increasing Hb electroactivity. Carbon-surface-oxide modification and Hb denaturation worked in tandem to maximally increase the Hb electroactivity in 60% methanol. While in ethanol and 1-propanol, the significant increases in Hb electroactivity caused by Hb denaturation were offset by an increase in Hb-inhibiting carbon surface oxides. Knowledge of these mechanisms shows the impact of alcohols on both Hb and carbon electrodes, allows for thoughtful design of the Hb-sensing system, is vital for proper analysis of Hb electroactivity in the presence of these alcohols (e.g., when used as binder solvents for immobilizing Hb into films), and provides fundamental understanding of the Hb-carbon interactions.

Nuclear localisation of 53BP1 is regulated by phosphorylation of the nuclear localisation signal.

PubMed

von Morgen, Patrick; Lidak, Tomas; Horejsi, Zuzana; Macurek, Libor

2018-06-01

Repair of damaged DNA is essential for maintaining genomic stability. TP53-binding protein 1 (53BP1) plays an important role in repair of the DNA double-strand breaks. Nuclear localisation of 53BP1 depends on importin β and nucleoporin 153, but the type and location of 53BP1 nuclear localisation signal (NLS) have yet to be determined. Here, we show that nuclear import of 53BP1 depends on two basic regions, namely 1667-KRK-1669 and 1681-KRGRK-1685, which are both needed for importin binding. Lysine 1667 is essential for interaction with importin and its substitution to arginine reduced nuclear localisation of 53BP1. Furthermore, we have found that CDK1-dependent phosphorylation of 53BP1 at S1678 impairs importin binding during mitosis. Phosphorylation-mimicking mutant S1678D showed reduced nuclear localisation, suggesting that phosphorylation of the NLS interferes with nuclear import of the 53BP1 CONCLUSIONS: We show that 53BP1 contains a classical bipartite NLS 1666-GKRKLITSEEERSPAKRGRKS-1686, which enables the importin-mediated nuclear transport of 53BP1. Additionally, we found that posttranslational modification within the NLS region can regulate 53BP1 nuclear import. Our results indicate that integrity of the NLS is important for 53BP1 nuclear localisation. Precise mapping of the NLS will facilitate further studies on the effect of posttranslational modifications and somatic mutations on the nuclear localisation 53BP1 and DNA repair. © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Molecular insight in gastric cancer induction: an overview of cancer stemness genes.

PubMed

Akhavan-Niaki, Haleh; Samadani, Ali Akbar

2014-04-01

Gastric cancer is one of the most outgoing human cancers in the world. Two main functional types were described: Intestinal adenocarcinoma and diffuse one. The most important purpose of this review is to analyze and investigate the main genetic factors involved in tumorogenesis of stomach and the molecular mechanism of their expression regulation alongside with the importance of cancer stem cells and their relationship with gastric cancer. It is evident that proper diagnosis of molecular case of cancer may lead to absolute treatment and at least reduction in the disease severity. However, stemness factors such as Sox2, Oct3/4, and Nanog were related with induced pluripotent stem cells, proposing a correlation between these stemness factors and cancer stem cells. Moreover, aberrant induction by Helicobacter pylori of the intestinal-specific homeobox transcription factors, CDX1 and CDX2, also plays an important role in this modification. There are some genes which are directly activated by CDX1 in gastric cancer and distinguished stemness-related reprogramming factors like SALL4 and KLF5. Correspondingly, we also aimed to present the main important epigenetic changes such as DNA methylation, histone modification, and chromatin modeling of stemness genes in disease development. Remarkably, a better understanding of molecular bases of cancer may lead to novel diagnostic, therapeutic, and preventive approaches by some genetic and epigenetic changes such as gene amplifications, gene silencing by DNA methylation, losses of imprinting, LOH, and mutations. Consequently, genome-wide searches of gene expression are widely important for surveying the proper mechanisms of cancer emergence and development. Conspicuously, this review explains an outline of the molecular mechanism and new approaches in gastric cancer.

Histone deacetylases play a major role in the transcriptional regulation of the Plasmodium falciparum life cycle.

PubMed

Chaal, Balbir K; Gupta, Archna P; Wastuwidyaningtyas, Brigitta D; Luah, Yen-Hoon; Bozdech, Zbynek

2010-01-22

The apparent paucity of molecular factors of transcriptional control in the genomes of Plasmodium parasites raises many questions about the mechanisms of life cycle regulation in these malaria parasites. Epigenetic regulation has been suggested to play a major role in the stage specific gene expression during the Plasmodium life cycle. To address some of these questions, we analyzed global transcriptional responses of Plasmodium falciparum to a potent inhibitor of histone deacetylase activities (HDAC). The inhibitor apicidin induced profound transcriptional changes in multiple stages of the P. falciparum intraerythrocytic developmental cycle (IDC) that were characterized by rapid activation and repression of a large percentage of the genome. A major component of this response was induction of genes that are otherwise suppressed during that particular stage of the IDC or specific for the exo-erythrocytic stages. In the schizont stage, apicidin induced hyperacetylation of histone lysine residues H3K9, H4K8 and the tetra-acetyl H4 (H4Ac4) and demethylation of H3K4me3. Interestingly, we observed overlapping patterns of chromosomal distributions between H4K8Ac and H3K4me3 and between H3K9Ac and H4Ac4. There was a significant but partial association between the apicidin-induced gene expression and histone modifications, which included a number of stage specific transcription factors. Taken together, inhibition of HDAC activities leads to dramatic de-regulation of the IDC transcriptional cascade, which is a result of both disruption of histone modifications and up-regulation of stage specific transcription factors. These findings suggest an important role of histone modification and chromatin remodeling in transcriptional regulation of the Plasmodium life cycle. This also emphasizes the potential of P. falciparum HDACs as drug targets for malaria chemotherapy.

Bioinformatics analysis reveals biophysical and evolutionary insights into the 3-nitrotyrosine post-translational modification in the human proteome

PubMed Central

Ng, John Y.; Boelen, Lies; Wong, Jason W. H.

2013-01-01

Protein 3-nitrotyrosine is a post-translational modification that commonly arises from the nitration of tyrosine residues. This modification has been detected under a wide range of pathological conditions and has been shown to alter protein function. Whether 3-nitrotyrosine is important in normal cellular processes or is likely to affect specific biological pathways remains unclear. Using GPS-YNO2, a recently described 3-nitrotyrosine prediction algorithm, a set of predictions for nitrated residues in the human proteome was generated. In total, 9.27 per cent of the proteome was predicted to be nitratable (27 922/301 091). By matching the predictions against a set of curated and experimentally validated 3-nitrotyrosine sites in human proteins, it was found that GPS-YNO2 is able to predict 73.1 per cent (404/553) of these sites. Furthermore, of these sites, 42 have been shown to be nitrated endogenously, with 85.7 per cent (36/42) of these predicted to be nitrated. This demonstrates the feasibility of using the predicted dataset for a whole proteome analysis. A comprehensive bioinformatics analysis was subsequently performed on predicted and all experimentally validated nitrated tyrosine. This found mild but specific biophysical constraints that affect the susceptibility of tyrosine to nitration, and these may play a role in increasing the likelihood of 3-nitrotyrosine to affect processes, including phosphorylation and DNA binding. Furthermore, examining the evolutionary conservation of predicted 3-nitrotyrosine showed that, relative to non-nitrated tyrosine residues, 3-nitrotyrosine residues are generally less conserved. This suggests that, at least in the majority of cases, 3-nitrotyrosine is likely to have a deleterious effect on protein function and less likely to be important in normal cellular function. PMID:23389939

The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE).

PubMed

Basu, Amitava; Dasari, Vasanthi; Mishra, Rakesh K; Khosla, Sanjeev

2014-01-01

DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that can read the histone code and translate it into DNA methylation. It plays an important role in the initiation of genomic imprints during gametogenesis and in nuclear reprogramming. With important functions attributed to it, it is imperative that the DNMT3L expression is tightly controlled. Previously, we had identified a CpG island within the human DNMT3L promoter and first exon that showed loss of DNA methylation in cancer samples. Here we show that this Differentially Methylated CpG island within DNMT3L (DNMT3L DMC) acts to repress transcription, is a Polycomb/Trithorax Response Element (PRE) and interacts with both PRC1 and PRC2 Polycomb repressive complexes. In addition, it adopts inactive chromatin conformation and is associated with other inactive chromatin-specific proteins like SUV39H1 and HP1. The presence of DNMT3L DMC also influences the adjacent promoter to adopt repressive histone post-translational modifications. Due to its association with multiple layers of repressive epigenetic modifications, we believe that PRE within the DNMT3L DMC is responsible for the tight regulation of DNMT3L expression and the aberrant epigenetic modifications of this region leading to DNMT3L overexpression could be the reason of nuclear programming during carcinogenesis.

Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for corneal stromal tissue engineering

PubMed Central

Lai, Jui-Yang; Li, Ya-Ting; Cho, Ching-Hsien; Yu, Ting-Chun

2012-01-01

Recent studies reflect the importance of using naturally occurring biopolymers as three-dimensional corneal keratocyte scaffolds and suggest that the porous structure of gelatin materials may play an important role in controlling nutrient uptake. In the current study, the authors further consider the application of carbodiimide cross-linked porous gelatin as an alternative to collagen for corneal stromal tissue engineering. The authors developed corneal keratocyte scaffolds by nanoscale modification of porous gelatin materials with chondroitin sulfate (CS) using carbodiimide chemistry. Scanning electron microscopy/energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy showed that the amount of covalently incorporated polysaccharide was significantly increased when the CS concentration was increased from 0% to 1.25% (w/v). In addition, as demonstrated by dimethylmethylene blue assays, the CS content in these samples was in the range of 0.078–0.149 nmol per 10 mg scaffold. When compared with their counterparts without CS treatment, various CS-modified porous gelatin membranes exhibited higher levels of water content, light transmittance, and amount of permeated nutrients but possessed lower Young’s modulus and resistance against protease digestion. The hydrophilic and mechanical properties of scaffolds modified with 0.25% CS were comparable with those of native corneas. The samples from this group were biocompatible with the rabbit corneal keratocytes and showed enhanced proliferative and biosynthetic capacity of cultured cells. In summary, the authors found that the nanoscale-level modification has influence on the characteristics and cell-material interactions of CS-containing gelatin hydrogels. Porous membranes with a CS content of 0.112 ± 0.003 nmol per 10 mg scaffold may hold potential for use in corneal stromal tissue engineering. PMID:22403490

Influence of the Surface Functional Group Density on the Carbon-Nanotube-Induced α-Chymotrypsin Structure and Activity Alterations.

PubMed

Zhao, Xingchen; Hao, Fang; Lu, Dawei; Liu, Wei; Zhou, Qunfang; Jiang, Guibin

2015-08-26

Because of the special properties of carbon nanotubes (CNTs), their applications have been introduced to many fields. The biosafety of these emerging materials is of high concern concomitantly. Because CNTs may initially bind with proteins in biofluids before they exert biological effects, it is of great importance to understand how the target proteins interact with these exogenous nanomaterials. Here we investigated the interaction between α-chymotrypsin (α-ChT) and carboxylized multiwalled CNTs in a simulated biophysical environment utilizing the techniques of fluorescence, UV-vis, circular dichroism spectroscopy, ζ potential, atomic force microscopy, and bicinchoninic acid analysis. It was demonstrated that CNTs interacted with α-ChT through electrostatic forces, causing a decrement in the α-helix and an increment in the β-sheet content of the protein. The protein fluorescence was quenched in a static mode. The increase in the surface modification density of CNTs enhanced the protein absorption and decreased the enzymatic activity correspondingly. α-ChT activity inhibition induced by CNTs with low surface modification density exhibited noncompetitive characteristics; however, a competitive feature was observed when CNTs with high surface modification density interacted with the protein. An increase of the ionic strength in the reaction buffer may help to reduce the interaction between CNTs and α-ChT because the high ionic strength may favor the release of the protein from binding on a CNT surface modified with functional groups. Accordingly, the functionalization density on the CNT surface plays an important role in the regulation of their biological effects and is worthy of concern when new modified CNTs are developed.

Radical SAM Enzymes in the Biosynthesis of Ribosomally Synthesized and Post-translationally Modified Peptides (RiPPs)

PubMed Central

Benjdia, Alhosna; Balty, Clémence; Berteau, Olivier

2017-01-01

Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are a large and diverse family of natural products. They possess interesting biological properties such as antibiotic or anticancer activities, making them attractive for therapeutic applications. In contrast to polyketides and non-ribosomal peptides, RiPPs derive from ribosomal peptides and are post-translationally modified by diverse enzyme families. Among them, the emerging superfamily of radical SAM enzymes has been shown to play a major role. These enzymes catalyze the formation of a wide range of post-translational modifications some of them having no counterparts in living systems or synthetic chemistry. The investigation of radical SAM enzymes has not only illuminated unprecedented strategies used by living systems to tailor peptides into complex natural products but has also allowed to uncover novel RiPP families. In this review, we summarize the current knowledge on radical SAM enzymes catalyzing RiPP post-translational modifications and discuss their mechanisms and growing importance notably in the context of the human microbiota. PMID:29167789

Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine.

PubMed

Ju, Tong; Niu, Wei; Guo, Jiantao

2016-09-16

Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

Shared Sulfur Mobilization Routes for tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Prokaryotes and Eukaryotes

PubMed Central

Leimkühler, Silke; Bühning, Martin; Beilschmidt, Lena

2017-01-01

Modifications of transfer RNA (tRNA) have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm5s2U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure. The trafficking and delivery of sulfur nucleosides is a complex process carried out by sulfur relay systems involving numerous proteins, which not only deliver sulfur to the specific tRNAs but also to other sulfur-containing molecules including iron–sulfur clusters, thiamin, biotin, lipoic acid and molybdopterin (MPT). Among the biosynthesis of these sulfur-containing molecules, the biosynthesis of the molybdenum cofactor (Moco) and the synthesis of thio-modified tRNAs in particular show a surprising link by sharing protein components for sulfur mobilization in pro- and eukaryotes. PMID:28098827

Assessment of the importance of the current-wave coupling in the shelf ocean forecasts

NASA Astrophysics Data System (ADS)

Jordà, G.; Bolaños, R.; Espino, M.; Sánchez-Arcilla, A.

2006-10-01

The effects of wave-current interactions on shelf ocean forecasts is investigated in the framework of the MFSTEP (Mediterranean Forecasting System Project Towards Enviromental Predictions) project. A one way sequential coupling approach is adopted to link the wave model (WAM) to the circulation model (SYMPHONIE). The coupling of waves and currents has been done considering four main processes: wave refraction due to currents, surface wind drag and bo€ttom drag modifications due to waves, and the wave induced mass flux. The coupled modelling system is implemented in the southern Catalan shelf (NW Mediterranean), a region with characteristics similar to most of the Mediterranean shelves. The sensitivity experiments are run in a typical operational configuration. The wave refraction by currents seems to be not very relevant in a microtidal context such as the western Mediterranean. The main effect of waves on current forecasts is through the modification of the wind drag. The Stokes drift also plays a significant role due to its spatial and temporal characteristics. Finally, the enhanced bottom friction is just noticeable in the inner shelf.

Phosphorylation of the IDP KID Modulates Affinity for KIX by Increasing the Lifetime of the Complex.

PubMed

Dahal, Liza; Shammas, Sarah L; Clarke, Jane

2017-12-19

Intrinsically disordered proteins (IDPs) are known to undergo a range of posttranslational modifications, but by what mechanism do such modifications affect the binding of an IDP to its partner protein? We investigate this question using one such IDP, the kinase inducible domain (KID) of the transcription factor CREB, which interacts with the KIX domain of CREB-binding protein upon phosphorylation. As with many other IDPs, KID undergoes coupled folding and binding to form α-helical structure upon interacting with KIX. This single site phosphorylation plays an important role in the control of transcriptional activation in vivo. Here we show that, contrary to expectation, phosphorylation has no effect on association rates-unphosphorylated KID binds just as rapidly as pKID, the phosphorylated form-but rather, acts by increasing the lifetime of the complex. We propose that by controlling the lifetime of the bound complex of pKID:KIX via altering the dissociation rate, phosphorylation can facilitate effective control of transcription regulation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Surface segregation of additives on SnO 2 based powders and their relationship with macroscopic properties

NASA Astrophysics Data System (ADS)

Pereira, Gilberto J.; Castro, Ricardo H. R.; Hidalgo, Pilar; Gouvêa, Douglas

2002-07-01

Surface properties of ceramic powders frequently play an important role in producing high-quality, high-performance, and reliable ceramic products. These properties are related to the surface bond types and interactions with the surroundings. Oxide surfaces generally contain adsorbed hydroxyl groups and modifications in the chemical composition of the surface may be studied by infrared spectroscopy. In this work, we prepared SnO 2 containing Fe or Mg ions by organic chemical route derived from Pechini's method. The prepared powders were characterized by infrared spectroscopy (FT-IR), X-ray diffraction (XRD), dynamic electrophoretic mobility and surface area determination. Results demonstrated that the studied additives segregate onto the oxide surface and modify the hydroxyl IR bands of the adsorbed hydroxyl groups. These surface modifications change some macroscopic properties of the powder such as the isoelectric point (IEP) in aqueous suspensions and the final specific surface area. The increase of the surface area with additive concentration is supposedly due to the reduction of surface energy of the powders when additives segregate on the powder surface.

Methanol steam reforming promoted by molten salt-modified platinum on alumina catalysts.

PubMed

Kusche, Matthias; Agel, Friederike; Ní Bhriain, Nollaig; Kaftan, Andre; Laurin, Mathias; Libuda, Jörg; Wasserscheid, Peter

2014-09-01

We herein describe a straight forward procedure to increase the performance of platinum-on-alumina catalysts in methanol steam reforming by applying an alkali hydroxide coating according to the "solid catalyst with ionic liquid layer" (SCILL) approach. We demonstrate by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed desorption (TPD) studies that potassium doping plays an important role in the catalyst activation. Moreover, the hygroscopic nature and the basicity of the salt modification contribute to the considerable enhancement in catalytic performance. During reaction, a partly liquid film of alkali hydroxides/carbonates forms on the catalyst/alumina surface, thus significantly enhancing the availability of water at the catalytically active sites. Too high catalyst pore fillings with salt introduce a considerable mass transfer barrier into the system as indicated by kinetic studies. Thus, the optimum interplay between beneficial catalyst modification and detrimental mass transfer effects had to be identified and was found on the applied platinum-on-alumina catalyst at KOH loadings around 7.5 mass%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A direct, ratiometric, and quantitative MALDI–MS assay for protein methyltransferases and acetyltransferases

PubMed Central

Richardson, Stacie L.; Hanjra, Pahul; Zhang, Gang; Mackie, Brianna D.; Peterson, Darrell L.; Huang, Rong

2016-01-01

Protein methylation and acetylation play important roles in biological processes, and misregulation of these modifications is involved in various diseases. Therefore, it is critical to understand the activities of the enzymes responsible for these modifications. Herein we describe a sensitive method for ratiometric quantification of methylated and acetylated peptides via MALDI-MS by direct spotting of enzymatic methylation and acetylation reaction mixtures without tedious purification procedures. The quantifiable detection limit for peptides with our method is approximately 10 fmol. This is achieved by increasing the signal-to-noise ratio through the addition of NH4H2PO4 to the matrix solution and reduction of the matrix α-cyanohydroxycinnamic acid concentration to 2 mg/ml. We have demonstrated the application of this method in enzyme kinetic analysis and inhibition studies. The unique feature of this method is the simultaneous quantification of multiple peptide species for investigation of processivity mechanisms. Its wide buffer compatibility makes it possible to be adapted to investigate the activity of any protein methyltransferase or acetyltransferase. PMID:25778392

Real Estate in the DNA Damage Response: Ubiquitin and SUMO Ligases Home in on DNA Double-Strand Breaks.

PubMed

Dantuma, Nico P; Pfeiffer, Annika

2016-01-01

Ubiquitin and the ubiquitin-like modifier SUMO are intimately connected with the cellular response to various types of DNA damage. A striking feature is the local accumulation of these proteinaceous post-translational modifications in the direct vicinity to DNA double-strand breaks, which plays a critical role in the formation of ionizing radiation-induced foci. The functional significance of these modifications is the coordinated recruitment and removal of proteins involved in DNA damage signaling and repair in a timely manner. The central orchestrators of these processes are the ubiquitin and SUMO ligases that are responsible for accurately tagging a broad array of chromatin and chromatin-associated proteins thereby changing their behavior or destination. Despite many differences in the mode of action of these enzymes, they share some striking features that are of direct relevance for their function in the DNA damage response. In this review, we outline the molecular mechanisms that are responsible for the recruitment of ubiquitin and SUMO ligases and discuss the importance of chromatin proximity in this process.

Obesogenic environment - intervention opportunities.

PubMed

Fisberg, Mauro; Maximino, Priscila; Kain, Juliana; Kovalskys, Irina

2016-01-01

To evaluate environmental obesogenic-related factors, such as physical activity in neighborhoods and schools, nutritional behavior, and intervention programs. Critical analysis of literature with personal point of view from infant obesity experts and political advisors for public intervention. Although obesity is a public health problem affecting several age groups, it is among children and adolescents that it plays a more important role, due to treatment complexity, high likelihood of persistence into adulthood, and association with other non-transmissible diseases while still in early age. Environment is a main component of the genesis and outcomes in the near future or long term. Modification of intake with high-density food, meal skipping, and high intake of saturated fat, sugar, and salt, associated to high levels of sedentarism are main causes of obesity. Intervention opportunities are related to modifications in political, environmental, and individual settings. School and physical activities in the educational environment are intertwined with nutrition intervention in continuous education. A critical review of some different scenarios in Latin American countries is presented. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling.

PubMed

Shi, Jianhua; Gu, Jin-hua; Dai, Chun-ling; Gu, Jianlan; Jin, Xiaoxia; Sun, Jianming; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

2015-09-28

Apoptosis plays an important role in neural development and neurological disorders. In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT. We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling.

Irreversible covalent modification of type I dehydroquinase with a stable Schiff base.

PubMed

Tizón, Lorena; Maneiro, María; Peón, Antonio; Otero, José M; Lence, Emilio; Poza, Sergio; van Raaij, Mark J; Thompson, Paul; Hawkins, Alastair R; González-Bello, Concepción

2015-01-21

The irreversible inhibition of type I dehydroquinase (DHQ1), the third enzyme of the shikimic acid pathway, is investigated by structural, biochemical and computational studies. Two epoxides, which are mimetics of the natural substrate, were designed as irreversible inhibitors of the DHQ1 enzyme and to study the binding requirements of the linkage to the enzyme. The epoxide with the S configuration caused the covalent modification of the protein whereas no reaction was obtained with its epimer. The first crystal structure of DHQ1 from Salmonella typhi covalently modified by the S epoxide, which is reported at 1.4 Å, revealed that the modified ligand is surprisingly covalently attached to the essential Lys170 by the formation of a stable Schiff base. The experimental and molecular dynamics simulation studies reported here highlight the huge importance of the conformation of the C3 carbon of the ligand for covalent linkage to this type of aldolase I enzyme, revealed the key role played by the essential His143 as a Lewis acid in this process and show the need for a neatly closed active site for catalysis.

Innovative approaches to nisin production.

PubMed

Özel, Burcu; Şimşek, Ömer; Akçelik, Mustafa; Saris, Per E J

2018-05-30

Nisin is a bacteriocin produced by Lactococcus lactis that has been approved by the Food Drug Administration for utilization as a GRAS status food additive. Nisin can inhibit spore germination and demonstrates antimicrobial activity against Listeria, Clostridium, Staphylococcus, and Bacillus species. Under some circumstances, it plays an immune modulator role and has a selective cytotoxic effect against cancer cells, although it is notable that the high production cost of nisin-a result of the low nisin production yield of producer strains-is an important factor restricting intensive use. In recent years, production of nisin has been significantly improved through genetic modifications to nisin producer strains and through innovative applications in the fermentation process. Recently, 15,400 IU ml -1 nisin production has been achieved in L. lactis cells following genetic modifications by eliminating the factors that negatively affect nisin biosynthesis or by increasing the cell density of the producing strains in the fermentation medium. In this review, innovative approaches related to cell and fermentation systems aimed at increasing nisin production are discussed and interpreted, with a view to increasing industrial nisin production.

BGDB: a database of bivalent genes

PubMed Central

Li, Qingyan; Lian, Shuabin; Dai, Zhiming; Xiang, Qian; Dai, Xianhua

2013-01-01

Bivalent gene is a gene marked with both H3K4me3 and H3K27me3 epigenetic modification in the same area, and is proposed to play a pivotal role related to pluripotency in embryonic stem (ES) cells. Identification of these bivalent genes and understanding their functions are important for further research of lineage specification and embryo development. So far, lots of genome-wide histone modification data were generated in mouse and human ES cells. These valuable data make it possible to identify bivalent genes, but no comprehensive data repositories or analysis tools are available for bivalent genes currently. In this work, we develop BGDB, the database of bivalent genes. The database contains 6897 bivalent genes in human and mouse ES cells, which are manually collected from scientific literature. Each entry contains curated information, including genomic context, sequences, gene ontology and other relevant information. The web services of BGDB database were implemented with PHP + MySQL + JavaScript, and provide diverse query functions. Database URL: http://dailab.sysu.edu.cn/bgdb/ PMID:23894186

Plasma Surface Modification for Immobilization of Bone Morphogenic Protein-2 on Polycaprolactone Scaffolds

NASA Astrophysics Data System (ADS)

Kim, Byung Hoon; Myung, Sung Woon; Jung, Sang Chul; Ko, Yeong Mu

2013-11-01

The immobilization of recombinant human bone formation protein-2 (rhBMP-2) on polycaprolactone (PCL) scaffolds was performed by plasma polymerization. RhBMP-2, which induces osteoblast differentiation in various cell types, is a growth factor that plays an important role in bone formation and repair. The surface of the PCL scaffold was functionalized with the carboxyl groups of plasma-polymerized acrylic acid (PPAA) thin films. Plasma polymerization was carried out at a discharge power of 60 W at an acrylic acid flow rate of 7 sccm for 5 min. The PPAA thin film exhibited moderate hydrophilic properties and possessed a high density of carboxyl groups. Carboxyl groups and rhBMP-2 on the PCL scaffolds surface were identified by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The alkaline phosphatase activity assay showed that the rhBMP-2 immobilized PCL scaffold increased the level of MG-63 cell differentiation. Plasma surface modification for the preparation of biomaterials, such as biofunctionalized polymer scaffolds, can be used for the binding of bioactive molecules in tissue engineering.

Polypeptide Functional Surface for the Aptamer Immobilization: Electrochemical Cocaine Biosensing.

PubMed

Bozokalfa, Guliz; Akbulut, Huseyin; Demir, Bilal; Guler, Emine; Gumus, Z Pınar; Odaci Demirkol, Dilek; Aldemir, Ebru; Yamada, Shuhei; Endo, Takeshi; Coskunol, Hakan; Timur, Suna; Yagci, Yusuf

2016-04-05

Electroanalytical technologies as a beneficial subject of modern analytical chemistry can play an important role for abused drug analysis which is crucial for both legal and social respects. This article reports a novel aptamer-based biosensing procedure for cocaine analysis by combining the advantages of aptamers as selective recognition elements with the well-known advantages of biosensor systems such as the possibility of miniaturization and automation, easy fabrication and modification, low cost, and sensitivity. In order to construct the aptasensor platform, first, polythiophene bearing polyalanine homopeptide side chains (PT-Pala) was electrochemically coated onto the surface of an electrode and then cocaine aptamer was attached to the polymer via covalent conjugation chemistry. The stepwise modification of the surface was confirmed by electrochemical characterization. The designed biosensing system was applied for the detection of cocaine and its metabolite, benzoylecgonine (BE), which exhibited a linear correlation in the range from 2.5 up to 10 nM and 0.5 up to 50 μM for cocaine and BE, respectively. In order to expand its practical application, the proposed method was successfully tested for the analysis of synthetic biological fluids.

Factors affecting caregivers' ability to make environmental modifications.

PubMed

Messecar, D C

2000-12-01

This study explored factors that family caregivers described as affecting their ability to use environmental modifications. Intensive interviews and participant observation were used to collect detailed data from 24 primary family caregivers. Several factors that affect the caregivers' ability to implement modification strategies were identified in the analysis. These factors included attributes of the elderly individual, attributes of the modification, quality of the caregiver-elderly relationship, caregivers' skills, personal resources of the caregiver, and the informal and formal supports available. Of these factors, the most important were the salient skills that caregivers need to implement environmental modifications. These findings point to the importance of caregivers receiving skills training in this important dimension of caregiving. Intervention should be based on a collaborative approach that ensures the caregiver and care receiver's needs and preferences are respected.

Vacuum-based surface modification of organic and metallic substrates

NASA Astrophysics Data System (ADS)

Torres, Jessica

Surface physico-chemical properties play an important role in the development and performance of materials in different applications. Consequently, understanding the chemical and physical processes involved during surface modification strategies is of great scientific and technological importance. This dissertation presents results from the surface modification of polymers, organic films and metallic substrates with reactive species, with the intent of simulating important modification processes and elucidating surface property changes of materials under different environments. The reactions of thermally evaporated copper and titanium with halogenated polytetrafluoroethylene (PTFE) and polyvinyl chloride (PVC) are used to contrast the interaction of metals with polymers. Results indicate that reactive metallization is thermodynamically favored when the metal-halogen bond strength is greater than the carbon-halogen bond strength. X-ray post-metallization treatment results in an increase in metal-halide bond formation due to the production of volatile halogen species in the polymer that react with the metallic overlayer. The reactions of atomic oxygen (AO) and atomic chlorine with polyethylene (PE) and self-assembled monolayers (SAMs) films were followed to ascertain the role of radical species during plasma-induced polymer surface modification. The reactions of AO with X-ray modified SAMs are initially the dominated by the incorporation of new oxygen containing functionality at the vacuum/film interface, leading to the production of volatile carbon containing species such as CO2 that erodes the hydrocarbon film. The reaction of atomic chlorine species with hydrocarbon SAMs, reveals that chlorination introduces C-Cl and C-Cl2 functionalities without erosion. A comparison of the reactions of AO and atomic chlorine with PE reveal a maximum incorporation of the corresponding C-O and C-Cl functionalities at the polymer surface. A novel method to prepare phosphorous-containing polymer surfaces through ion implantation of trimethyl phosphine onto PE is presented. Air exposure of the resulting P-implanted PE leads to the surface selective oxidation of phosphorous moieties. P-containing hydrocarbon films are used to model the surface chemical changes of P-containing polymers exposed to AO. Results indicate that oxidized phosphorous species protect the film from AO-induced erosion. The low temperature (<150 K) oxidation of nitrided iron surfaces exposed to oxygen reveal the formation of iron oxynitride (FexNyO z, nitrosonium ions (NO+) as well as nitrite/nitrito and nitrate type species. The production of nitrite/nitrito and nitrate species is taken as evidence for the existence of oxygen insertion chemistry into the iron nitride lattice under these low temperature oxidation conditions. Upon annealing the oxidized iron nitride surface, nitrogen desorbs exclusively as nitric oxide (NO).

Repeat expansion disease: Progress and puzzles in disease pathogenesis

PubMed Central

La Spada, Albert R.; Taylor, J. Paul

2015-01-01

Repeat expansion mutations cause at least 22 inherited neurological diseases. The complexity of repeat disease genetics and pathobiology has revealed unexpected shared themes and mechanistic pathways among the diseases, for example, RNA toxicity. Also, investigation of the polyglutamine diseases has identified post-translational modification as a key step in the pathogenic cascade, and has shown that the autophagy pathway plays an important role in the degradation of misfolded proteins – two themes likely to be relevant to the entire neurodegeneration field. Insights from repeat disease research are catalyzing new lines of study that should not only elucidate molecular mechanisms of disease, but also highlight opportunities for therapeutic intervention for these currently untreatable disorders. PMID:20177426

Right heart on multidetector CT

PubMed Central

Gopalan, D

2011-01-01

Right ventricular function plays an integral role in the pathogenesis and outcome of many cardiovascular diseases. Imaging the right ventricle has long been a challenge because of its complex geometry. In recent years there has been a tremendous expansion in multidetector row CT (MDCT) and its cardiac applications. By judicious modification of contrast medium protocol, it is possible to achieve good opacification of the right-sided cardiac chambers, thereby paving the way for exploring the overshadowed right heart. This article will describe the key features of right heart anatomy, review MDCT acquisition techniques, elaborate the various morphological and functional information that can be obtained, and illustrate some important clinical conditions associated with an abnormal right heart. PMID:22723537

Proteomics for understanding miRNA biology

PubMed Central

Huang, Tai-Chung; Pinto, Sneha M.; Pandey, Akhilesh

2013-01-01

MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in posttranscriptional regulation of gene expression. Mature miRNAs associate with the RNA interference silencing complex to repress mRNA translation and/or degrade mRNA transcripts. Mass spectrometry-based proteomics has enabled identification of several core components of the canonical miRNA processing pathway and their posttranslational modifications which are pivotal in miRNA regulatory mechanisms. The use of quantitative proteomic strategies has also emerged as a key technique for experimental identification of miRNA targets by allowing direct determination of proteins whose levels are altered because of translational suppression. This review focuses on the role of proteomics and labeling strategies to understand miRNA biology. PMID:23125164

Small ubiquitin-related modifier is secreted and shows cytokine-like activity.

PubMed

Hosono, Hidetaka; Yokosawa, Hideyoshi

2008-05-01

Small ubiquitin-related modifier (SUMO) is a type I ubiquitin-like protein family member and is covalently attached to various target proteins. Through this post-translational modification, SUMO plays important roles in various cellular events. Here, we show that SUMO is secreted from cultured cells in an endoplasmic reticulum (ER)/Golgi-independent manner and that this secretion occurs without covalent binding to target proteins or chain formation. Overexpression experiments using C-terminally truncated mutants of SUMO revealed that the secretion requires the C-terminal sequence. Recombinant SUMO-3 protein was capable of binding to and promoting the proliferation of cultured cells. Thus, we propose that SUMO functions as a cytokine-like molecule extracellularly.

Crystal structure of the Tum1 protein from the yeast Saccharomyces cerevisiae.

PubMed

Qiu, Rui; Wang, Fengbin; Liu, Meiruo; Lou, Tiantian; Ji, Chaoneng

2012-11-01

Yeast tRNA-thiouridine modification protein 1 (Tum1) plays essential role in the sulfur transfer process of Urm1 system, which in turn is involved in many important cellular processes. In the rhodanese-like domain (RLD), conserved cysteine residue is proved to be the centre of active site of sulfurtransferases and crucial for the substrate recognition. In this report, we describe the crystal structure of Tum1 protein at 1.90 A resolution which, despite consisting of two RLDs, has only one conserved cysteine residue in the C-terminal RLD. An unaccounted electron density is found near the active site, which might point to the new cofactor in the sulfur transfer mechanism.

ADP-ribosyl-N₃: A Versatile Precursor for Divergent Syntheses of ADP-ribosylated Compounds.

PubMed

Li, Lingjun; Li, Qianqian; Ding, Shengqiang; Xin, Pengyang; Zhang, Yuqin; Huang, Shenlong; Zhang, Guisheng

2017-08-14

Adenosine diphosphate-ribose (ADP-ribose) and its derivatives play important roles in a series of complex physiological procedures. The design and synthesis of artificial ADP-ribosylated compounds is an efficient way to develop valuable chemical biology tools and discover new drug candidates. However, the synthesis of ADP-ribosylated compounds is currently difficult due to structural complexity, easily broken pyrophosphate bond and high hydrophilicity. In this paper, ADP-ribosyl-N₃ was designed and synthesized for the first time. With ADP-ribosyl-N₃ as the key precursor, a divergent post-modification strategy was developed to prepare structurally diverse ADP-ribosylated compounds including novel nucleotides and peptides bearing ADP-ribosyl moieties.

Evidences for dry deintercalation in layered compounds upon controlled surface charging in x-ray photoelectron spectroscopy

NASA Astrophysics Data System (ADS)

Feldman, Y.; Zak, A.; Tenne, R.; Cohen, H.

2003-09-01

Pronounced surface diffusion is observed during x-ray photoelectron spectroscopy measurements of 2H platelets and inorganic fullerene-like (IF) MS2 (M=W,Mo) powders, intercalated with alkaline (A=K,Na) elements. Using controlled surface charging the intercalants migrate towards the surface, where they oxidize. This dry deintercalation is controllable via external charging parameters, yet showing that internal chemical and structural parameters play an important role in the process. Diffusion rates out of 2H matrixes are generally higher than in corresponding IF samples. Clear differences are also found between Mo and W-based systems. Application of this approach into surface modification and processing is proposed.

S-nitrosylation of the thioredoxin-like domains of protein disulfide isomerase and its role in neurodegenerative conditions.

NASA Astrophysics Data System (ADS)

Conway, Myra; Harris, Matthew

2015-04-01

Correct protein folding and inhibition of protein aggregation is facilitated by a cellular ‘quality control system’ that engages a network of protein interactions including molecular chaperones and the ubiquitin proteasome system. Key chaperones involved in these regulatory mechanisms are the protein disulphide isomerases (PDI) and their homologues, predominantly expressed in the endoplasmic reticulum of most tissues. Redox changes that disrupt ER homeostasis can lead to modification of these enzymes or chaperones with the loss of their proposed neuroprotective role resulting in an increase in protein misfolding. Misfolded protein aggregates have been observed in several disease states and are considered to play a pivotal role in the pathogenesis of neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral sclerosis. This review will focus on the importance of the thioredoxin-like -CGHC- active site of PDI and how our understanding of this structural motif will play a key role in unravelling the pathogenic mechanisms that underpin these neurodegenerative conditions.

Exploiting tRNAs to Boost Virulence

PubMed Central

Albers, Suki; Czech, Andreas

2016-01-01

Transfer RNAs (tRNAs) are powerful small RNA entities that are used to translate nucleotide language of genes into the amino acid language of proteins. Their near-uniform length and tertiary structure as well as their high nucleotide similarity and post-transcriptional modifications have made it difficult to characterize individual species quantitatively. However, due to the central role of the tRNA pool in protein biosynthesis as well as newly emerging roles played by tRNAs, their quantitative assessment yields important information, particularly relevant for virus research. Viruses which depend on the host protein expression machinery have evolved various strategies to optimize tRNA usage—either by adapting to the host codon usage or encoding their own tRNAs. Additionally, several viruses bear tRNA-like elements (TLE) in the 5′- and 3′-UTR of their mRNAs. There are different hypotheses concerning the manner in which such structures boost viral protein expression. Furthermore, retroviruses use special tRNAs for packaging and initiating reverse transcription of their genetic material. Since there is a strong specificity of different viruses towards certain tRNAs, different strategies for recruitment are employed. Interestingly, modifications on tRNAs strongly impact their functionality in viruses. Here, we review those intersection points between virus and tRNA research and describe methods for assessing the tRNA pool in terms of concentration, aminoacylation and modification. PMID:26797637

Environmental chemical exposures and human epigenetics

PubMed Central

Hou, Lifang; Zhang, Xiao; Wang, Dong; Baccarelli, Andrea

2012-01-01

Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes. PMID:22253299

Imagining a brighter future: the effect of positive imagery training on mood, prospective mental imagery and emotional bias in older adults.

PubMed

Murphy, Susannah E; Clare O'Donoghue, M; Drazich, Erin H S; Blackwell, Simon E; Christina Nobre, Anna; Holmes, Emily A

2015-11-30

Positive affect and optimism play an important role in healthy ageing and are associated with improved physical and cognitive health outcomes. This study investigated whether it is possible to boost positive affect and associated positive biases in this age group using cognitive training. The effect of computerised imagery-based cognitive bias modification on positive affect, vividness of positive prospective imagery and interpretation biases in older adults was measured. 77 older adults received 4 weeks (12 sessions) of imagery cognitive bias modification or a control condition. They were assessed at baseline, post-training and at a one-month follow-up. Both groups reported decreased negative affect and trait anxiety, and increased optimism across the three assessments. Imagery cognitive bias modification significantly increased the vividness of positive prospective imagery post-training, compared with the control training. Contrary to our hypothesis, there was no difference between the training groups in negative interpretation bias. This is a useful demonstration that it is possible to successfully engage older adults in computer-based cognitive training and to enhance the vividness of positive imagery about the future in this group. Future studies are needed to assess the longer-term consequences of such training and the impact on affect and wellbeing in more vulnerable groups. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Recognition of Double Stranded RNA by Guanidine-Modified Peptide Nucleic Acids (GPNA)

PubMed Central

Gupta, Pankaj; Muse, Oluwatoyosi; Rozners, Eriks

2011-01-01

Double helical RNA has become an attractive target for molecular recognition because many non-coding RNAs play important roles in control of gene expression. Recently, we discovered that short peptide nucleic acids (PNA) bind strongly and sequence selectively to a homopurine tract of double helical RNA via triple helix formation. Herein we tested if the molecular recognition of RNA can be enhanced by α-guanidine modification of PNA. Our study was motivated by the discovery of Ly and co-workers that the guanidine modification greatly enhances the cellular delivery of PNA. Isothermal titration calorimetry showed that the guanidine-modified PNA (GPNA) had reduced affinity and sequence selectivity for triple helical recognition of RNA. The data suggested that in contrast to unmodified PNA, which formed a 1:1 PNA-RNA triple helix, GPNA preferred a 2:1 GPNA-RNA triplex-invasion complex. Nevertheless, promising results were obtained for recognition of biologically relevant double helical RNA. Consistent with enhanced strand invasion ability, GPNA derived from D-arginine recognized the transactivation response element (TAR) of HIV-1 with high affinity and sequence selectivity, presumably via Watson-Crick duplex formation. On the other hand, strong and sequence selective triple helices were formed by unmodified and nucelobase-modified PNAs and the purine rich strand of bacterial A-site. These results suggest that appropriate chemical modifications of PNA may enhance molecular recognition of complex non-coding RNAs. PMID:22146072

Myeloperoxidase-dependent Inactivation of Surfactant Protein D in Vitro and in Vivo*

PubMed Central

Crouch, Erika C.; Hirche, Tim O.; Shao, Baohai; Boxio, Rachel; Wartelle, Julien; Benabid, Rym; McDonald, Barbara; Heinecke, Jay; Matalon, Sadis; Belaaouaj, Azzaq

2010-01-01

Surfactant protein D (SP-D) plays diverse and important roles in innate immunity and pulmonary homeostasis. Neutrophils and myeloperoxidase (MPO) colocalized with SP-D in a murine bacterial pneumonia model of acute inflammation, suggesting that MPO-derived reactive species might alter the function of SP-D. Exposure of SP-D to the complete MPO-H2O2-halide system caused loss of SP-D-dependent aggregating activity. Hypochlorous acid (HOCl), the major oxidant generated by MPO, caused a similar loss of aggregating activity, which was accompanied by the generation of abnormal disulfide-cross-linked oligomers. A full-length SP-D mutant lacking N-terminal cysteine residues and truncation mutants lacking the N-terminal domains were resistant to the oxidant-induced alterations in disulfide bonding. Mass spectroscopy of HOCl-treated human SP-D demonstrated several modifications, but none involved key ligand binding residues. There was detectable oxidation of cysteine 15, but no HOCl-induced cysteine modifications were observed in the C-terminal lectin domain. Together, the findings localize abnormal disulfide cross-links to the N-terminal domain. MPO-deficient mice showed decreased cross-linking of SP-D and increased SP-D-dependent aggregating activity in the pneumonia model. Thus, MPO-derived oxidants can lead to modifications of SP-D structure with associated alterations in its characteristic aggregating activity. PMID:20228064

An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

PubMed

Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan

2015-12-07

As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

Global analysis of DNA methylation in young (J1) and senescent (J2) Gossypium hirsutum L. cotyledons by MeDIP-Seq

PubMed Central

Dou, Lingling; Jia, Xiaoyun; Wei, Hengling; Fan, Shuli; Wang, Hantao; Guo, Yaning; Duan, Shan; Pang, Chaoyou; Yu, Shuxun

2017-01-01

DNA methylation is an important epigenetic modification regulating gene expression, genomic imprinting, transposon silencing and chromatin structure in plants and plays an important role in leaf senescence. However, the DNA methylation pattern during Gossypium hirsutum L. cotyledon senescence is poorly understood. In this study, global DNA methylation patterns were compared between two cotyledon development stages, young (J1) and senescence (J2), using methylated DNA immunoprecipitation (MeDIP-Seq). Methylated cytosine occurred mostly in repeat elements, especially LTR/Gypsy in both J1 and J2. When comparing J1 against J2, there were 1222 down-methylated genes and 623 up-methylated genes. Methylated genes were significantly enriched in carbohydrate metabolism, biosynthesis of other secondary metabolites and amino acid metabolism pathways. The global DNA methylation level decreased from J1 to J2, especially in gene promoters, transcriptional termination regions and regions around CpG islands. We further investigated the expression patterns of 9 DNA methyltransferase-associated genes and 2 DNA demethyltransferase-associated genes from young to senescent cotyledons, which were down-regulated during cotyledon development. In this paper, we first reported that senescent cotton cotyledons exhibited lower DNA methylation levels, primarily due to decreased DNA methyltransferase activity and which also play important role in regulating secondary metabolite process. PMID:28715427

Advancing pig cloning technologies towards application in regenerative medicine.

PubMed

Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

2012-08-01

Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

Non-metabolic functions of glycolytic enzymes in tumorigenesis.

PubMed

Yu, X; Li, S

2017-05-11

Cancer cells reprogram their metabolism to meet the requirement for survival and rapid growth. One hallmark of cancer metabolism is elevated aerobic glycolysis and reduced oxidative phosphorylation. Emerging evidence showed that most glycolytic enzymes are deregulated in cancer cells and play important roles in tumorigenesis. Recent studies revealed that all essential glycolytic enzymes can be translocated into nucleus where they participate in tumor progression independent of their canonical metabolic roles. These noncanonical functions include anti-apoptosis, regulation of epigenetic modifications, modulation of transcription factors and co-factors, extracellular cytokine, protein kinase activity and mTORC1 signaling pathway, suggesting that these multifaceted glycolytic enzymes not only function in canonical metabolism but also directly link metabolism to epigenetic and transcription programs implicated in tumorigenesis. These findings underscore our understanding about how tumor cells adapt to nutrient and fuel availability in the environment and most importantly, provide insights into development of cancer therapy.

Regulation of Stem Cell Aging by Metabolism and Epigenetics.

PubMed

Ren, Ruotong; Ocampo, Alejandro; Liu, Guang-Hui; Izpisua Belmonte, Juan Carlos

2017-09-05

Stem cell aging and exhaustion are considered important drivers of organismal aging. Age-associated declines in stem cell function are characterized by metabolic and epigenetic changes. Understanding the mechanisms underlying these changes will likely reveal novel therapeutic targets for ameliorating age-associated phenotypes and for prolonging human healthspan. Recent studies have shown that metabolism plays an important role in regulating epigenetic modifications and that this regulation dramatically affects the aging process. This review focuses on current knowledge regarding the mechanisms of stem cell aging, and the links between cellular metabolism and epigenetic regulation. In addition, we discuss how these interactions sense and respond to environmental stress in order to maintain stem cell homeostasis, and how environmental stimuli regulate stem cell function. Additionally, we highlight recent advances in the development of therapeutic strategies to rejuvenate dysfunctional aged stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part I).

PubMed

Wang, Fuzhou; Stefano, George B; Kream, Richard M

2014-06-25

DRG is of importance in relaying painful stimulation to the higher pain centers and therefore could be a crucial target for early intervention aimed at suppressing primary afferent stimulation. Complex regional pain syndrome (CRPS) is a common pain condition with an unknown etiology. Recently added new information enriches our understanding of CRPS pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, and mechanisms of pain modulation, central sensitization, and autonomic functions in CRPS revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of CRPS. Epigenetics refers to mitotically and meiotically heritable changes in gene expression that do not affect the DNA sequence. As epigenetic modifications potentially play an important role in inflammatory cytokine metabolism, neurotransmitter responsiveness, and analgesic sensitivity, they are likely key factors in the development of chronic pain. In this dyad review series, we systematically examine the nerve injury-related changes in the neurological system and their contribution to CRPS. In this part, we first reviewed and summarized the role of neural sensitization in DRG neurons in performing function in the context of pain processing. Particular emphasis is placed on the cellular and molecular changes after nerve injury as well as different models of inflammatory and neuropathic pain. These were considered as the potential molecular bases that underlie nerve injury-associated pathogenesis of CRPS.

Transcriptome Dynamics during Maize Endosperm Development

PubMed Central

Feng, Jiaojiao; Xu, Shutu; Wang, Lei; Li, Feifei; Li, Yibo; Zhang, Renhe; Zhang, Xinghua; Xue, Jiquan; Guo, Dongwei

2016-01-01

The endosperm is a major organ of the seed that plays vital roles in determining seed weight and quality. However, genome-wide transcriptome patterns throughout maize endosperm development have not been comprehensively investigated to date. Accordingly, we performed a high-throughput RNA sequencing (RNA-seq) analysis of the maize endosperm transcriptome at 5, 10, 15 and 20 days after pollination (DAP). We found that more than 11,000 protein-coding genes underwent alternative splicing (AS) events during the four developmental stages studied. These genes were mainly involved in intracellular protein transport, signal transmission, cellular carbohydrate metabolism, cellular lipid metabolism, lipid biosynthesis, protein modification, histone modification, cellular amino acid metabolism, and DNA repair. Additionally, 7,633 genes, including 473 transcription factors (TFs), were differentially expressed among the four developmental stages. The differentially expressed TFs were from 50 families, including the bZIP, WRKY, GeBP and ARF families. Further analysis of the stage-specific TFs showed that binding, nucleus and ligand-dependent nuclear receptor activities might be important at 5 DAP, that immune responses, signalling, binding and lumen development are involved at 10 DAP, that protein metabolic processes and the cytoplasm might be important at 15 DAP, and that the responses to various stimuli are different at 20 DAP compared with the other developmental stages. This RNA-seq analysis provides novel, comprehensive insights into the transcriptome dynamics during early endosperm development in maize. PMID:27695101

The prediction of palmitoylation site locations using a multiple feature extraction method.

PubMed

Shi, Shao-Ping; Sun, Xing-Yu; Qiu, Jian-Ding; Suo, Sheng-Bao; Chen, Xiang; Huang, Shu-Yun; Liang, Ru-Ping

2013-03-01

As an extremely important and ubiquitous post-translational lipid modification, palmitoylation plays a significant role in a variety of biological and physiological processes. Unlike other lipid modifications, protein palmitoylation and depalmitoylation are highly dynamic and can regulate both protein function and localization. The dynamic nature of palmitoylation is poorly understood because of the limitations in current assay methods. The in vivo or in vitro experimental identification of palmitoylation sites is both time consuming and expensive. Due to the large volume of protein sequences generated in the post-genomic era, it is extraordinarily important in both basic research and drug discovery to rapidly identify the attributes of a new protein's palmitoylation sites. In this work, a new computational method, WAP-Palm, combining multiple feature extraction, has been developed to predict the palmitoylation sites of proteins. The performance of the WAP-Palm model is measured herein and was found to have a sensitivity of 81.53%, a specificity of 90.45%, an accuracy of 85.99% and a Matthews correlation coefficient of 72.26% in 10-fold cross-validation test. The results obtained from both the cross-validation and independent tests suggest that the WAP-Palm model might facilitate the identification and annotation of protein palmitoylation locations. The online service is available at http://bioinfo.ncu.edu.cn/WAP-Palm.aspx. Copyright © 2013 Elsevier Inc. All rights reserved.

Distinct 3-O-Sulfated Heparan Sulfate Modification Patterns Are Required for kal-1−Dependent Neurite Branching in a Context-Dependent Manner in Caenorhabditis elegans

PubMed Central

Tecle, Eillen; Diaz-Balzac, Carlos A.; Bülow, Hannes E.

2013-01-01

Heparan sulfate (HS) is an unbranched glycosaminoglycan exhibiting substantial molecular diversity due to multiple, nonuniformly introduced modifications, including sulfations, epimerization, and acetylation. HS modifications serve specific and instructive roles in neuronal development, leading to the hypothesis of a HS code that regulates nervous system patterning. Although the in vivo roles of many of the HS modifications have been investigated, very little is known about the function of HS 3-O-sulfation in vivo. By examining patterning of the Caenorhabditis elegans nervous system in loss of function mutants of the two 3-O-sulfotransferases, hst-3.1 and hst-3.2, we found HS 3-O-sulfation to be largely dispensable for overall neural development. However, generation of stereotypical neurite branches in hermaphroditic-specific neurons required hst-3.1, hst-3.2, as well as an extracellular cell adhesion molecule encoded by kal-1, the homolog of Kallmann Syndrome associated gene 1/anosmin-1. In contrast, kal-1−dependent neurite branching in AIY neurons required catalytic activity of hst-3.2 but not hst-3.1. The context-dependent requirement for hst-3.2 and hst-3.1 indicates that both enzymes generate distinct types of HS modification patterns in different cell types, which regulate kal-1 to promote neurite branching. We conclude that HS 3-O-sulfation does not play a general role in establishing the HS code in C. elegans but rather plays a specialized role in a context-dependent manner to establish defined aspects of neuronal circuits. PMID:23451335

Endogenous S-sulfhydration of PTEN helps protect against modification by nitric oxide

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

Ohno, Kazuki; Okuda, Kosaku; Uehara, Takashi, E-mail: uehara@pharm.okayama-u.ac.jp

2015-01-02

Highlights: • PTEN is S-sulfhydrated endogenously in SH-SY5Y human neuroblastoma cells. • Preventing this modification by knocking down CBS renders PTEN sensitive to NO. • pAkt levels are increased significantly in CBS siRNA-transfected cells. • H{sub 2}S functions as an endogenous regulator of PTEN in neuronal cells. - Abstract: Hydrogen sulfide (H{sub 2}S) is a gaseous regulatory factor produced by several enzymes, and plays a pivotal role in processes such as proliferation or vasodilation. Recent reports demonstrated the physiological and pathophysiological functions of H{sub 2}S in neurons. PTEN is a target of nitric oxide (NO) or hydrogen peroxide, and themore » oxidative modification of cysteine (Cys) residue(s) attenuates its enzymatic activity. In the present study, we assessed the effect of H{sub 2}S on the direct modification of PTEN and the resulting downstream signaling. A modified biotin switch assay in SH-SY5Y human neuroblastoma cells revealed that PTEN is S-sulfhydrated endogenously. Subsequently, site-directed mutagenesis demonstrated that both Cys71 and Cys124 in PTEN are targets for S-sulfhydration. Further, the knockdown of cystathionine β-synthetase (CBS) using siRNA decreased this modification in a manner that was correlated to amount of H{sub 2}S. PTEN was more sensitive to NO under these conditions. These results suggest that the endogenous S-sulfhydration of PTEN via CBS/H{sub 2}S plays a role in preventing the S-nitrosylation that would inhibition its enzymatic activity under physiological conditions.« less

Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.

PubMed

Wesolowski, Jordan; Weber, Mary M; Nawrotek, Agata; Dooley, Cheryl A; Calderon, Mike; St Croix, Claudette M; Hackstadt, Ted; Cherfils, Jacqueline; Paumet, Fabienne

2017-05-02

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. IMPORTANCE Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex. Copyright © 2017 Wesolowski et al.

Permuting the PGF Signature Motif Blocks both Archaeosortase-Dependent C-Terminal Cleavage and Prenyl Lipid Attachment for the Haloferax volcanii S-Layer Glycoprotein.

PubMed

Abdul Halim, Mohd Farid; Karch, Kelly R; Zhou, Yitian; Haft, Daniel H; Garcia, Benjamin A; Pohlschroder, Mechthild

2015-12-28

For years, the S-layer glycoprotein (SLG), the sole component of many archaeal cell walls, was thought to be anchored to the cell surface by a C-terminal transmembrane segment. Recently, however, we demonstrated that the Haloferax volcanii SLG C terminus is removed by an archaeosortase (ArtA), a novel peptidase. SLG, which was previously shown to be lipid modified, contains a C-terminal tripartite structure, including a highly conserved proline-glycine-phenylalanine (PGF) motif. Here, we demonstrate that ArtA does not process an SLG variant where the PGF motif is replaced with a PFG motif (slg(G796F,F797G)). Furthermore, using radiolabeling, we show that SLG lipid modification requires the PGF motif and is ArtA dependent, lending confirmation to the use of a novel C-terminal lipid-mediated protein-anchoring mechanism by prokaryotes. Similar to the case for the ΔartA strain, the growth, cellular morphology, and cell wall of the slg(G796F,F797G) strain, in which modifications of additional H. volcanii ArtA substrates should not be altered, are adversely affected, demonstrating the importance of these posttranslational SLG modifications. Our data suggest that ArtA is either directly or indirectly involved in a novel proteolysis-coupled, covalent lipid-mediated anchoring mechanism. Given that archaeosortase homologs are encoded by a broad range of prokaryotes, it is likely that this anchoring mechanism is widely conserved. Prokaryotic proteins bound to cell surfaces through intercalation, covalent attachment, or protein-protein interactions play critical roles in essential cellular processes. Unfortunately, the molecular mechanisms that anchor proteins to archaeal cell surfaces remain poorly characterized. Here, using the archaeon H. volcanii as a model system, we report the first in vivo studies of a novel protein-anchoring pathway involving lipid modification of a peptidase-processed C terminus. Our findings not only yield important insights into poorly understood aspects of archaeal biology but also have important implications for key bacterial species, including those of the human microbiome. Additionally, insights may facilitate industrial applications, given that photosynthetic cyanobacteria encode uncharacterized homologs of this evolutionarily conserved enzyme, or may spur development of unique drug delivery systems. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Control of peroxisome proliferator-activated receptor gamma2 stability and activity by SUMOylation.

PubMed

Floyd, Z Elizabeth; Stephens, Jacqueline M

2004-06-01

To determine whether small ubiquitin-related modifier (SUMO)ylation of lysine 107 plays a role in regulating the activity of peroxisome proliferator-activated receptor gamma (PPARgamma). Transient expression of wild-type and K107R-PPARgamma2 in the NIH 3T3 fibroblast cell line was carried out in conjunction with half-life studies, luciferase activity assays, and indirect immunofluorescence localization studies. Additional in vitro analysis was carried out using recombinant SUMOylation pathway proteins along with in vitro transcribed and translated wild-type or K107R-PPARgamma2 to examine the SUMO-1 modification state of wild-type and SUMO-deficient K107R-PPARgamma2. While examining PPARgamma2 for potential ubiquitylation sites, we identified a strong consensus site for SUMO modification that contains lysine 107. In vitro, SUMOylation studies showed that lysine 107 of PPARgamma2 is a major SUMOylation site and that at least one other SUMOylation site is present in PPARgamma. In addition, our results demonstrated that SUMO-1 affects PPARgamma stability and transcriptional activity but not the nuclear localization of PPARgamma. These results indicated that SUMOylation plays a role in regulating PPARgamma, both indirectly and directly by modification of lysine 107. Because PPARgamma is regulated in numerous animal models of obesity, understanding the covalent modifications of PPARgamma may enhance our understanding of the metabolic syndrome.

Sterol glycosyltransferases--the enzymes that modify sterols.

PubMed

Chaturvedi, Pankaj; Misra, Pratibha; Tuli, Rakesh

2011-09-01

Sterols are important components of cell membranes, hormones, signalling molecules and defense-related biotic and abiotic chemicals. Sterol glycosyltransferases (SGTs) are enzymes involved in sterol modifications and play an important role in metabolic plasticity during adaptive responses. The enzymes are classified as a subset of family 1 glycosyltransferases due to the presence of a signature motif in their primary sequence. These enzymes follow a compulsory order sequential mechanism forming a ternary complex. The diverse applications of sterol glycosides, like cytotoxic and apoptotic activity, anticancer activity, medicinal values, anti-stress roles and anti-insect and antibacterial properties, draws attention towards their synthesis mechanisms. Many secondary metabolites are derived from sterol pathways, which are important in defense mechanisms against pathogens. SGTs in plants are involved in changed sensitivity to stress hormones and their agrochemical analogs and changed tolerance to biotic and abiotic stresses. SGTs that glycosylate steroidal hormones, such as brassinosteroids, function as growth and development regulators in plants. In terms of metabolic roles, it can be said that SGTs occupy important position in plant metabolism and may offer future tools for crop improvement.

Overview of Medicinally Important Diterpenoids Derived from Plastids.

PubMed

Zhang, Linsu; Lu, Shanfa

2017-01-01

FL 32608 Terpenoids are hydrocarbon compounds derived from common fivecarbon isoprene (C5H8) building blocks. They are formed through the condensation and subsequent modification of isoprene units in various ways including - among others - cyclization and/or oxygenation. Their synthesis is localized either to the chloroplast and/or to the cytoplasm/peroxisome/ endoplasmic reticulum and mitochondrion. Terpenoids represent a very large and diverse class of metabolites and play important roles in plant growth and development. In addition, they have been intensively used in human health care, disease treatment and in dietary supplements. Approximately 60% of natural products known so far are terpenoids. This review briefly summarizes the biosynthetic pathways of major plant terpenoids. Then, five well-known and medicinally important diterpenoids, including paclitaxel, tanshinone, ginkgolide, triptolide and oridonin are discussed in detail. Their structures, occurrence, extraction and identification methods, pharmacological properties and clinical uses are also reviewed. Finally, the prospects of using biotechnology to produce medicinally important terpenoids are also briefly discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Facebook Role Play Addiction - A Comorbidity with Multiple Compulsive-Impulsive Spectrum Disorders.

PubMed

Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

2016-06-01

Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive-compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive-compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study.

Facebook Role Play Addiction – A Comorbidity with Multiple Compulsive–Impulsive Spectrum Disorders

PubMed Central

Nathan, Deeepa; Shukla, Lekhansh; Kandasamy, Arun; Benegal, Vivek

2016-01-01

Background Problematic Internet use (PIU) is an emerging entity with varied contents. Behavioral addictions have high comorbidity of attention deficit hyperactivity disorder and obsessive–compulsive spectrum disorders. Social networking site (SNS) addiction and role playing game (RPG) addiction are traditionally studied as separate entities. We present a case with excessive Internet use, with a particular focus on phenomenology and psychiatric comorbidities. Case presentation Fifteen-year-old girl with childhood onset attention deficit disorder, obsessive–compulsive disorder, adolescent onset trichotillomania, and disturbed family environment presented with excessive Facebook use. Main online activity was creating profiles in names of mainstream fictional characters and assuming their identity (background, linguistic attributes, etc.). This was a group activity with significant socialization in the virtual world. Craving, salience, withdrawal, mood modification, and conflict were clearly elucidated and significant social and occupational dysfunction was evident. Discussion This case highlights various vulnerability and sociofamilial factors contributing to behavioral addiction. It also highlights the presence of untreated comorbidities in such cases. The difference from contemporary RPGs and uniqueness of role playing on SNS is discussed. SNS role playing as a separate genre of PIU and its potential to reach epidemic proportions are discussed. Conclusions Individuals with temperamental vulnerability are likely to develop behavioral addictions. Identification and management of comorbid conditions are important. The content of PIU continues to evolve and needs further study. PMID:27156380

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A low-cost, high-efficiency and high-flexibility surface modification technology for a black bisphenol A polycarbonate board

NASA Astrophysics Data System (ADS)

Wang, Suhuan; Liu, Jianguo; Lv, Ming; Zeng, Xiaoyan

2014-09-01

In this paper, a low-cost, high-efficiency and high-flexibility surface modification technology for polymer materials was achieved at high laser scanning speeds (600-1000 mm s-1) and using an all-solid state, Q-switched, high-average power, and nanosecond pulse ultraviolet (355 nm wavelength) laser. During the surface modification of a very important engineering plastic, i.e., black bisphenol A polycarbonate (BAPC) board, it was found that different laser parameters (e.g., laser fluence and pulse frequency) were able to result in different surface microstructures (e.g., many tiny protuberances or a porous microstructure with periodical V-type grooves). After the modification, although the total relative content of the oxygen-containing groups (e.g., Csbnd O and COO-) on the BAPC surface increased, however, the special microstructures played a deciding role in the surface properties (e.g., contact angle and surface energy) of the BAPC. The change trend of the water contact angle on the BAPC surface was with an obvious increase, that of the diiodomethane contact angle was with a most decrease, and that of the ethylene glycol contact angle was between the above two. It showed that the wetting properties of the three liquids on the modified BAPC surface were different. Basing on the measurements of the contact angles of the three liquids, and according to the Young equation and the Lifshitz van der Waals and Lewis acid-base theory, the BAPC surface energy after the modification was calculated. The results were that, in a broad range of laser fluences, pulse frequencies and scanning speeds, the surface energy had a significant increase (e.g., from the original of about 44 mJ m-2 to the maximum of about 70 mJ m-2), and the higher the laser pulse frequency, the more significant the increase. This would be very advantageous to fabricate the high-quality micro-devices and micro-systems on the modified surface.

Posttranscriptional RNA Modifications: playing metabolic games in a cell's chemical Legoland.

PubMed

Helm, Mark; Alfonzo, Juan D

2014-02-20

Nature combines existing biochemical building blocks, at times with subtlety of purpose. RNA modifications are a prime example of this, where standard RNA nucleosides are decorated with chemical groups and building blocks that we recall from our basic biochemistry lectures. The result: a wealth of chemical diversity whose full biological relevance has remained elusive despite being public knowledge for some time. Here, we highlight several modifications that, because of their chemical intricacy, rely on seemingly unrelated pathways to provide cofactors for their synthesis. Besides their immediate role in affecting RNA function, modifications may act as sensors and transducers of information that connect a cell's metabolic state to its translational output, carefully orchestrating a delicate balance between metabolic rate and protein synthesis at a system's level. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

NASA Astrophysics Data System (ADS)

Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

2015-05-01

Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

Conducting participatory photography with children with disabilities: a literature review.

PubMed

Eisen, Isabel; Cunningham, Barbara Jane; Campbell, Wenonah

2018-03-28

This review summarized studies that used participatory photography with children with disabilities, including those with communication impairments, and described modifications made to the methodology to facilitate their participation in qualitative research. In the fall of 2016, we searched Psycinfo (OVID), ERIC, CINAHL and Web of Science to identify studies that used participatory photography with children with disabilities. The search was repeated in January 2018 to retrieve any new publications. The first author extracted data that described the characteristics of each study and the modifications used. Of the 258 articles identified, 19 met inclusion criteria. Participants ranged from 4-21 years old and had a variety of disabilities. Study topics included education, leisure activities and adulthood. Researchers modified participatory photography to enhance accessibility by: modifying cameras; providing individual training; teaching consent through role play; allowing children to direct adults to take photographs; including additional forms of media; using diaries and questionnaires; providing individual interviews with simplified questions; using multiple forms of communication; and modifying how photographs are shared. Participatory photography can be an effective method for studying the lived experiences of children with disabilities, particularly those with communication impairments. Methodological modifications can enhance the accessibility of this approach for this population. Implications for Rehabilitation Participatory photography may be an effective qualitative research method for learning about the perspectives and experiences of children with disabilities on a wide array of topics. There are many specific modifications that researchers can use to support the inclusion of children with disabilities in participatory photography research. The findings of studies that use participatory photography methodology may provide rehabilitation professionals with important insights into the lives of children with disabilities.

Proteome-wide detection and quantitative analysis of irreversible cysteine oxidation using long column UPLC-pSRM.

PubMed

Lee, Chia-Fang; Paull, Tanya T; Person, Maria D

2013-10-04

Reactive oxygen species (ROS) play an important role in normal biological functions and pathological processes. ROS is one of the driving forces for oxidizing proteins, especially on cysteine thiols. The labile, transient, and dynamic nature of oxidative modifications poses enormous technical challenges for both accurate modification site determination and quantitation of cysteine thiols. The present study describes a mass spectrometry-based approach that allows effective discovery and quantification of irreversible cysteine modifications. The utilization of a long reverse phase column provides high-resolution chromatography to separate different forms of modified cysteine thiols from protein complexes or cell lysates. This Fourier transform mass spectrometry (FT-MS) approach enabled detection and quantitation of ataxia telangiectasia mutated (ATM) complex cysteine sulfoxidation states using Skyline MS1 filtering. When we applied the long column ultra high pressure liquid chromatography (UPLC)-MS/MS analysis, 61 and 44 peptides from cell lysates and cells were identified with cysteine modifications in response to in vitro and in vivo H2O2 oxidation, respectively. Long column ultra high pressure liquid chromatography pseudo selected reaction monitoring (UPLC-pSRM) was then developed to monitor the oxidative level of cysteine thiols in cell lysate under varying concentrations of H2O2 treatment. From UPLC-pSRM analysis, the dynamic conversion of sulfinic (S-O2H) and sulfonic acid (S-O3H) was observed within nucleoside diphosphate kinase (Nm23-H1) and heat shock 70 kDa protein 8 (Hsc70). These methods are suitable for proteome-wide studies, providing a highly sensitive, straightforward approach to identify proteins containing redox-sensitive cysteine thiols in biological systems.

The influence of a behavior modification interventional program on body mass index in obese adolescents.

PubMed

Toulabi, Tahereh; Khosh Niyat Nikoo, Mohsen; Amini, Fariba; Nazari, Hedayat; Mardani, Mahnaz

2012-03-01

The prevalence of obesity and overweight among children and adolescents is increasing rapidly. The present research was performed to determine the influence of a ''behavior modification'' program on body mass index (BMI) in obese public high school students in Iran. In this study, 152 adolescence and their parents were selected from 12 high schools of Khorram Abad from 2004 to 2006, and they were randomly assigned to either the intervention or the control groups. The "behavior modification" interventional program consisted of nutritional education, modifying dietary habits, teaching exercise programs, teaching nutritional facts to the parents, and performing exercises 3 days a week. The height and weight as well as waist, hip, and wrist circumferences of the participants were measured before and after implementing the interventional program. BMI and waist to hip ratio (WHR) were calculated. The adolescents and parents completed a nutrition knowledge questionnaire. Adolescents also completed the Beck's Depression Questionnaire. Adolescent's mean weight, BMI, and waist and hip circumferences decreased significantly after implementing the interventional program, in the intervention group (p≤0.001). In addition, the students' and parents' nutrition knowledge increased in the intervention group after implementing the interventional program (p<0.046). The symptoms of depression decreased and the frequency of students without symptoms of depression increased in the case group, but it did not reveal a statistically significant difference between case and control groups. The ''behavior modification'' interventional program is effective in reducing BMI in obese students, and therefore, school principals and planners can play an important role in controlling obesity by implementing this program via the students, their parents, and the school staff. Copyright © 2012. Published by Elsevier B.V.

Lysine-Directed Post-translational Modifications of Tau Protein in Alzheimer's Disease and Related Tauopathies

PubMed Central

Kontaxi, Christiana; Piccardo, Pedro; Gill, Andrew C.

2017-01-01

Tau is a microtubule-associated protein responsible mainly for stabilizing the neuronal microtubule network in the brain. Under normal conditions, tau is highly soluble and adopts an “unfolded” conformation. However, it undergoes conformational changes resulting in a less soluble form with weakened microtubule stabilizing properties. Altered tau forms characteristic pathogenic inclusions in Alzheimer's disease and related tauopathies. Although, tau hyperphosphorylation is widely considered to be the major trigger of tau malfunction, tau undergoes several post-translational modifications at lysine residues including acetylation, methylation, ubiquitylation, SUMOylation, and glycation. We are only beginning to define the site-specific impact of each type of lysine modification on tau biology as well as the possible interplay between them, but, like phosphorylation, these modifications are likely to play critical roles in tau's normal and pathobiology. This review summarizes the latest findings focusing on lysine post-translational modifications that occur at both endogenous tau protein and pathological tau forms in AD and other tauopathies. In addition, it highlights the significance of a site-dependent approach of studying tau post-translational modifications under normal and pathological conditions. PMID:28848737

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis.

PubMed

Yan, Xiaochen; Pan, Bo; Lv, Tiewei; Liu, Lingjuan; Zhu, Jing; Shen, Wen; Huang, Xupei; Tian, Jie

2017-01-05

Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells. These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.

S-nitrosylation in the regulation of gene transcription☆

PubMed Central

Sha, Yonggang; Marshall, Harvey E.

2015-01-01

Background Post-translational modification of proteins by S-nitrosylation serves as a major mode of signaling in mammalian cells and a growing body of evidence has shown that transcription factors and their activating pathways are primary targets. S-nitrosylation directly modifies a number of transcription factors, including NF-κB, HIF-1, and AP-1. In addition, S-nitrosylation can indirectly regulate gene transcription by modulating other cell signaling pathways, in particular JNK kinase and ras. Scope of review The evolution of S-nitrosylation as a signaling mechanism in the regulation of gene transcription, physiological advantages of protein S-nitrosylation in the control of gene transcription, and discussion of the many transcriptional proteins modulated by S-nitrosylation is summarized. Major conclusions S-nitrosylation plays a crucial role in the control of mammalian gene transcription with numerous transcription factors regulated by this modification. Many of these proteins serve as immunomodulators, and inducible nitric oxide synthase (iNOS) is regarded as a principal mediatiator of NO-dependent S-nitrosylation. However, additional targets within the nucleus (e.g. histone deacetylases) and alternative mechanisms of S-nitrosylation (e.g. GAPDH-mediated trans-nitrosylation) are thought to play a role in NOS-dependent transcriptional regulation. General significance Derangement of SNO-regulated gene transcription is an important factor in a variety of pathological conditions including neoplasia and sepsis. A better understanding of protein S-nitrosylation as it relates to gene transcription and the physiological mechanisms behind this process is likely to lead to novel therapies for these disorders. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation. PMID:21640163

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

PubMed

Xie, Yongjing; Min, Soyoung; Harte, Níal P; Kirk, Hannah; O'Brien, John E; Voorheis, H Paul; Svanborg, Catharina; Hun Mok, K

2013-01-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions. Copyright © 2012 Wiley Periodicals, Inc.

Protein Thiol Redox Signaling in Monocytes and Macrophages.

PubMed

Short, John D; Downs, Kevin; Tavakoli, Sina; Asmis, Reto

2016-11-20

Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death. Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases. The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal. 25, 816-835.

Modification of oral dosage forms for the older adult: An Irish prevalence study.

PubMed

Mc Gillicuddy, Aoife; Kelly, Maria; Sweeney, Catherine; Carmichael, Ann; Crean, Abina M; Sahm, Laura J

2016-08-20

Age-related pharmacological changes complicate oral dosage form (ODF) suitability for older adults. The aim of this study was to investigate the appropriateness of ODF for older adults by determining the prevalence of ODF modifications in an aged care facility in Ireland. Drug charts for eligible patients were obtained. Details of all medications administered were recorded. ODF modifications were examined to determine if they were evidence-based: defined as complying with the product license or best practice guidelines (BPG). In total, of 111 patients, 35.1% received at least one modified medicine. Medicines were most commonly modified to facilitate fractional dosing (82.0%). Of the 68 instances of medicine modification, 35.3% complied with the product license. Of the 44 unlicensed modifications, 14 complied with BPG. Therefore, 44.1% of modifications were not evidence-based. This study highlights that clinicians have to routinely tailor commercial ODF to meet older patients' needs despite the lack of an evidence-base for almost half of these modifications. The main factor contributing to these modifications is the lack of appropriate, licensed dosage forms. However, reimbursement policies also play a role. Research is needed to optimise medicine administration and to provide clinicians with much needed evidence to support their daily practice. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Strigolactones in Nutrient-Stress Responses in Plants

PubMed Central

Marzec, Marek; Muszynska, Aleksandra; Gruszka, Damian

2013-01-01

Strigolactones (SLs) are a new group of plant hormones, which have been intensively investigated during the last few years. The wide spectrum of SLs actions, including the regulation of shoot/root architecture, and the stimulation of the interactions between roots and fungi or bacteria, as well as the stimulation of germination of parasitic plants, indicates that this group of hormones may play an important role in the mechanisms that control soil exploration, and the root-mediated uptake of nutrients. Current studies have shown that SLs might be factors that have an influence on the plant response to a deficiency of macronutrients. Experimental data from the last four years have confirmed that the biosynthesis and exudation of SLs are increased under phosphorus and nitrogen deficiency. All these data suggest that SLs may regulate the complex response to nutrient stress, which include not only the modification of the plant developmental process, but also the cooperation with other organisms in order to minimize the effects of threats. In this paper the results of studies that indicate that SLs play an important role in the response to nutrient stress are reviewed and the consequences of the higher biosynthesis and exudation of SLs in response to phosphorus and nitrogen deficiency are discussed. PMID:23629665

Epigenetics: The missing link to understanding β-cell dysfunction in the pathogenesis of type 2 diabetes

PubMed Central

Gilbert, Elizabeth R.; Liu, Dongmin

2012-01-01

Type 2 diabetes (T2D) is a growing health problem worldwide. While peripheral insulin resistance is common during obesity and aging in both animals and people, progression to T2D is largely due to insulin secretory dysfunction and significant apoptosis of functional β-cells, leading to an inability to compensate for insulin resistance. It is recognized that environmental factors and nutrition play an important role in the pathogenesis of diabetes. However, our knowledge surrounding molecular mechanisms by which these factors trigger β-cell dysfunction and diabetes is still limited. Recent discoveries raise the possibility that epigenetic changes in response to environmental stimuli may play an important role in the development of diabetes. In this paper, we review emerging knowledge regarding epigenetic mechanisms that may be involved in β-cell dysfunction and pathogenesis of diabetes, including the role of nutrition, oxidative stress and inflammation. We will mainly focus on the role of DNA methylation and histone modifications but will also briefly review data on miRNA effects on the pancreatic islets. Further studies aimed at better understanding how epigenetic regulation of gene expression controls β-cell function may reveal potential therapeutic targets for prevention and treatment of diabetes. PMID:22810088

The balance between caseins and whey proteins in cow's milk determines its allergenicity.

PubMed

Lara-Villoslada, F; Olivares, M; Xaus, J

2005-05-01

Cow's milk allergy is quite common in the first years of human life. Protein composition plays an important role in this pathology, particularly the casein/whey protein ratio. It is known that milks from different species have different sensitization capacities although their protein sources are quite similar. Thus, the objective of this work was to compare the allergenicity of native cow's milk and milk with a modified ratio of casein and whey proteins in a murine model of atopy. Twenty-four Balb/c mice were orally sensitized to native cow's milk or modified cow's milk with a casein/whey protein ratio of 40:60. During the sensitization period, the number of mice suffering from diarrhea was significantly higher in the native cow's milk-sensitized group than in the modified milk-sensitized group. Once mice were killed, plasma histamine levels were shown to be significantly higher in native cow's milk-sensitized mice. In addition, cow's milk proteins induced a higher lymphocyte sensitization in the native milk-sensitized mice, with a significant increase in the specific proliferation ratio of these cells. These results suggest that the balance between caseins and whey proteins plays an important role in the sensitization capacity of cow's milk, and its modification might be a way to reduce the allergenicity of cow's milk.

The histone methyltransferase Smyd2 is a negative regulator of macrophage activation by suppressing interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) production.

PubMed

Xu, Guiliang; Liu, Guilin; Xiong, Sidong; Liu, Haiyan; Chen, Xi; Zheng, Biao

2015-02-27

SET and MYND domain-containing 2 (Smyd2), a histone 3 lysine 4- and histone 3 lysine 36 (H3K36)-specific methyltransferase, plays critical roles in cardiac development and tumorigenesis. However, the role of Smyd2 in immunity and inflammation remains poorly understood. In this study, we report that Smyd2 is a novel negative regulator for macrophage activation and M1 polarization. Elevated Smyd2 expression suppresses the production of proinflammatory cytokines, including IL-6 and TNF, and inhibits the expression of important cell surface molecules, including major MHC-II and costimulatory molecules. Furthermore, macrophages with high Smyd2 expression inhibit Th-17 cell differentiation but promote regulatory T cell differentiation as a result of increased TGF-β production and decreased IL-6 secretion. In macrophages, Smyd2 specifically facilitates H3K36 dimethylation at Tnf and Il6 promoters to suppress their transcription and inhibits NF-κB and ERK signaling. Therefore, our data demonstrate that epigenetic modification by Smyd2-mediated H3K36 dimethylation at Tnf and Il6 promoters plays an important role in the regulation of macrophage activation during inflammation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Microbiome and bacterial translocation in cirrhosis.

PubMed

Gómez-Hurtado, Isabel; Such, José; Francés, Rubén

2016-12-01

Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis. Copyright © 2015 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

Thermal biology mediates responses of amphibians and reptiles to habitat modification.

PubMed

Nowakowski, A Justin; Watling, James I; Thompson, Michelle E; Brusch, George A; Catenazzi, Alessandro; Whitfield, Steven M; Kurz, David J; Suárez-Mayorga, Ángela; Aponte-Gutiérrez, Andrés; Donnelly, Maureen A; Todd, Brian D

2018-03-01

Human activities often replace native forests with warmer, modified habitats that represent novel thermal environments for biodiversity. Reducing biodiversity loss hinges upon identifying which species are most sensitive to the environmental conditions that result from habitat modification. Drawing on case studies and a meta-analysis, we examined whether observed and modelled thermal traits, including heat tolerances, variation in body temperatures, and evaporative water loss, explained variation in sensitivity of ectotherms to habitat modification. Low heat tolerances of lizards and amphibians and high evaporative water loss of amphibians were associated with increased sensitivity to habitat modification, often explaining more variation than non-thermal traits. Heat tolerances alone explained 24-66% (mean = 38%) of the variation in species responses, and these trends were largely consistent across geographic locations and spatial scales. As habitat modification alters local microclimates, the thermal biology of species will likely play a key role in the reassembly of terrestrial communities. © 2018 John Wiley & Sons Ltd/CNRS.

Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1

PubMed Central

Chang, Chuang-Rung; Blackstone, Craig

2017-01-01

Mitochondria in cells comprise a tubulovesicular network shaped continuously by complementary fission and fusion events. The mammalian Drp1 protein plays a key role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in the balance between these opposing processes can occur rapidly, indicating that modifications to these proteins may regulate mitochondrial membrane dynamics. We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized. This dynamin-related GTPase undergoes a number of steps to mediate mitochondrial fission, including translocation from cytoplasm to the mitochondrial outer membrane, higher-order assembly into spirals, GTP hydrolysis associated with a conformational change and membrane deformation, and ultimately disassembly. Many of these steps may be influenced by covalent modification of Drp1. We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. PMID:20649536

Infection and body odours: evolutionary and medical perspectives.

PubMed

Prugnolle, Franck; Lefèvre, Thierry; Renaud, François; Møller, Anders Pape; Missé, Dorothée; Thomas, Frédéric

2009-09-01

Infections are often followed by a change in body odours. For a long time, these changes were considered as non-specific (with no adaptive value) but recent evidences suggest that this may not always be true. Odour modifications due to an infection may either be of adaptive value for the parasite or the host. Here, we describe the observations in support of this idea, discuss the potential roles these modifications may play for the parasite and the host and propose a set of future directions that we think should allow to better understand the mechanisms at the origin of these modifications and how they may be used by both parasites and their human hosts.

Use of meteorological satellite observations in weather modification programs

NASA Technical Reports Server (NTRS)

Dennis, A. S.; Smith, P. L., Jr.; Biswas, K. R.

1973-01-01

The potential value of weather satellite data in field operations of weather modification is appraised. It was found that satellites could play a useful role in operational weather modification projects, particularly in the recognition of treatment opportunities. Satellite cloud photographs and infrared observations appear promising in the identification of treatment opportunities in seeding orographic cloud systems for increased snowpack, in seeding convective clouds for increased rainfall, in identifying hail threats, and in tracking and observing hurricanes as an aid to timing and location of seeding treatments. It was concluded that the potential value of satellite data in the treatment and evaluation phases of operational projects is not as great as in the recognition of treatment opportunity.

tRNA modification profiles of the fast-proliferating cancer cells

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

Dong, Chao; Niu, Leilei; Song, Wei

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In additionmore » to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.« less

Nanodiscs in Membrane Biochemistry and Biophysics.

PubMed

Denisov, Ilia G; Sligar, Stephen G

2017-03-22

Membrane proteins play a most important part in metabolism, signaling, cell motility, transport, development, and many other biochemical and biophysical processes which constitute fundamentals of life on the molecular level. Detailed understanding of these processes is necessary for the progress of life sciences and biomedical applications. Nanodiscs provide a new and powerful tool for a broad spectrum of biochemical and biophysical studies of membrane proteins and are commonly acknowledged as an optimal membrane mimetic system that provides control over size, composition, and specific functional modifications on the nanometer scale. In this review we attempted to combine a comprehensive list of various applications of nanodisc technology with systematic analysis of the most attractive features of this system and advantages provided by nanodiscs for structural and mechanistic studies of membrane proteins.

Minireview: roles of the forkhead transcription factor FOXL2 in granulosa cell biology and pathology.

PubMed

Pisarska, Margareta D; Barlow, Gillian; Kuo, Fang-Ting

2011-04-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells.

Plant salt-tolerance mechanisms

DOE PAGES

Deinlein, Ulrich; Stephan, Aaron B.; Horie, Tomoaki; ...

2014-06-01

Crop performance is severely affected by high salt concentrations in soils. To engineer more salt-tolerant plants it is crucial to unravel the key components of the plant salt-tolerance network. Here we review our understanding of the core salt-tolerance mechanisms in plants. Recent studies have shown that stress sensing and signaling components can play important roles in regulating the plant salinity stress response. We also review key Na+ transport and detoxification pathways and the impact of epigenetic chromatin modifications on salinity tolerance. In addition, we discuss the progress that has been made towards engineering salt tolerance in crops, including marker-assisted selectionmore » and gene stacking techniques. We also identify key open questions that remain to be addressed in the future.« less

Monomeric and polymeric forms of ependymin: a brain extracellular glycoprotein implicated in memory consolidation processes.

PubMed

Shashoua, V E

1988-07-01

Ependymin, a brain extracellular glycoprotein that appears to be implicated in neural circuit modifications associated with the process of memory consolidation, can rapidly polymerize into fibrous aggregates when the Ca2+ concentration in solution is reduced by the addition of EGTA or by dialysis. Such aggregates, once formed, could not be redissolved in boiling 1% SDS in 6 M urea, acetic acid, saturated aqueous potassium thiocyanate, and trifluoroacetic acid. They were, however, soluble in formic acid. Investigations of the immunological properties of ependymin indicated that various monomers, oligomers and polymers of the molecule with differing carbohydrate contents can be obtained. The polymerization properties of the ependymins may play an important role in their functions in memory consolidation mechanisms.

Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte

PubMed Central

Kumar, Suresh N.; Konorev, Eugene A.; Aggarwal, Deepika; Kalyanaraman, Balaraman

2011-01-01

Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48 h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity. PMID:21338723

Minireview: Roles of the Forkhead Transcription Factor FOXL2 in Granulosa Cell Biology and Pathology

PubMed Central

Barlow, Gillian; Kuo, Fang-Ting

2011-01-01

The forkhead transcription factor (FOXL2) is an essential transcription factor in the ovary. It is important in ovarian development and a key factor in female sex determination. In addition, FOXL2 plays a significant role in the postnatal ovary and follicle maintenance. The diverse transcriptional activities of FOXL2 are likely attributable to posttranslational modifications and binding to other key proteins involved in granulosa cell function. Mutations of FOXL2 lead to disorders of ovarian function ranging from premature follicle depletion and ovarian failure to unregulated granulosa cell proliferation leading to tumor formation. Thus, FOXL2 is a key regulator of granulosa cell function and a master transcription factor in these cells. PMID:21248146

On the robustness of the primordial power spectrum in renormalized Higgs inflation

NASA Astrophysics Data System (ADS)

Bezrukov, Fedor; Pauly, Martin; Rubio, Javier

2018-02-01

We study the cosmological consequences of higher-dimensional operators respecting the asymptotic symmetries of the tree-level Higgs inflation action. The main contribution of these operators to the renormalization group enhanced potential is localized in a compact field range, whose upper limit is close to the end of inflation. The spectrum of primordial fluctuations in the so-called universal regime turns out to be almost insensitive to radiative corrections and in excellent agreement with the present cosmological data. However, higher-dimensional operators can play an important role in critical Higgs inflation scenarios containing a quasi-inflection point along the inflationary trajectory. The interplay of radiative corrections with this quasi-inflection point may translate into a sizable modification of the inflationary observables.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Irradiation Effects in Fosterrite and the Nature of Interstellar Grains: A Coordinated Spectroscopy and Electron Microscopy Study

NASA Technical Reports Server (NTRS)

Keller, Lindsay P.; Christoffersen, R.

2007-01-01

Crystalline and amorphous silicates condense in the outflows of low mass evolved stars and massive red supergiant stars and are injected into the interstellar medium (ISM) where they are rendered almost completely amorphous by a multitude of destructive processes (e.g. shock, grain-grain collisions, and irradiation). Irradiation effects in particular may have played an important role in the genesis and modification of primitive grains in cometary dust, but unraveling those effects requires controlled experiments under appropriate conditions and with an emphasis on materials relevant to the ISM. Here we report our infrared (IR) microspectroscopy and trans-mission electron microscope (TEM) measurements on forsterite that was amorphized through irradiation by high energy heavy ions.

Planning satellite communication services and spectrum-orbit utilization

NASA Technical Reports Server (NTRS)

Sawitz, P. H.

1982-01-01

The relationship between approaches to planning satellite communication services and spectrum-orbit utilization is considered, with emphasis on the fixed-satellite and the broadcasting-satellite services. It is noted that there are several possible approaches to planning space services, differing principally in the rigidity with which technical parameters are prescribed, in the time for which a plan remains in force, and in the procedures adopted for implementation and modifications. With some planning approaches, spectrum-orbit utilization is fixed at the time the plan is made. Others provide for greater flexibility by making it possible to postpone some decisions on technical parameters. In addition, the two political questions of what is equitable access and how it can be guaranteed in practice play an important role.

MODIFICATION OF SEA ANEMONE BEHAVIOR BY SYMBIOTIC ZOOXANTHELLAE: EXPANSION AND CONTRACTION.

PubMed

Pearse, Vicki Buchsbaum

1974-12-01

The pattern of expansion and contraction by the sea anemone Anthopleura elegantissima differs in individuals with or without endosymbiotic zooxanthellae. Anemones without zooxanthellae, found in dark habitats, do not regularly expand or contract under changes in light. Anemones with zooxanthellae expand in moderate light and contract in intense light or in darkness, with striking uniformity. However, this behavior does not always depend directly on the presence of zooxanthellae. Anemones that have previously had endosymbiotic zooxanthellae subsequently expand and contract with changes in light in the absence of these algae. Thus, conditioned responses may be involved. It is suggested that expansion and contraction of the anemones may play an important role in favorably regulating the amount of light to which their zooxanthellae are exposed.

MODIFICATION OF SEA ANEMONE BEHAVIOR BY SYMBIOTIC ZOOXANTHELLAE: PHOTOTAXIS.

PubMed

Pearse, Vicki Buchsbaum

1974-12-01

The sea anemone Anthopleura elegantissima, with and without endosymbiotic zooxanthellae, was tested for evidence of phototactic behavior. Anemones with zooxanthellae always displayed phototaxis, either positive or negative depending on the experimental light intensity and the light intensity of the habitat from which the animals were taken. Anemones without zooxanthellae-even those that had previously harbored zooxanthellae and that were genetically identical clone-mates of phototactic individuals-never displayed phototaxis, appearing completely indifferent to light and shade. The results indicate that phototaxis in this sea anemone depends directly on the presence of its symbiotic algae. It is suggested that the flexible phototactic behavior of the anemone may play an important role in favorably regulating the amount of light to which the zooxanthellae are exposed.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae

PubMed Central

Kim, Minkyu; Buratowski, Stephen; Schreiber, Stuart L; Friedman, Nir

2005-01-01

Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur in a great number of independent, meaningful combinations. Published low-resolution microarray studies on the combinatorial complexity of histone modification patterns suffer from confounding effects caused by the averaging of modification levels over multiple nucleosomes. To overcome this problem, we used a high-resolution tiled microarray with single-nucleosome resolution to investigate the occurrence of combinations of 12 histone modifications on thousands of nucleosomes in actively growing S. cerevisiae. We found that histone modifications do not occur independently; there are roughly two groups of co-occurring modifications. One group of lysine acetylations shows a sharply defined domain of two hypo-acetylated nucleosomes, adjacent to the transcriptional start site, whose occurrence does not correlate with transcription levels. The other group consists of modifications occurring in gradients through the coding regions of genes in a pattern associated with transcription. We found no evidence for a deterministic code of many discrete states, but instead we saw blended, continuous patterns that distinguish nucleosomes at one location (e.g., promoter nucleosomes) from those at another location (e.g., over the 3′ ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role. PMID:16122352

Epigenetic modifications: An important mechanism in diabetic disturbances.

PubMed

Rorbach-Dolata, Anna; Kubis, Adriana; Piwowar, Agnieszka

2017-11-29

In the search for explanations of diabetes pathomechanisms, especially the development of its vascular complications (micro- and macrovascular ), although current, good metabolic control of diabetes, attention was drawn to the role of epigenetic inheritance associated with epigenetic modifications of histone proteins and DNA in hyperglycemia conditions. This study showed the significant role of DNA methylation and histone epigenetic modifications (a different nature and a different degree) in the transmission of information that is not connected with gene inheritance but concerns the persistent changes induced by hyperglycemia..Attention was paid to the role of DNA methylation of pancreatic cells in the pathogenesis of type 1 diabetes, but also type 2. The important role of DNA methylation changes in a so-called intrauterine growth restriction (IUGR) as reason of subsequent development of diabetes was particularly emphasized. In the pathogenesis of type 2 diabetes and its complications, especially microvascular complications, the greatest share and importance of epigenetic modifications on mitochondrial DNA metylation are the most important. The multidirectionality Complicaand complexity of epigenetic modifications of histone proteins indicate their importance in the development of diabetic disturbances. An especially important role is attributed to methylation and acetylation of histone proteins, in particular on arginine and lysine, whose changes occur most frequently. Moreover, epigenetic modifications of the enzymes, especially methylases, responsible for these processes are the underlying. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may be a useful prognostic biomarker of susceptibility to the disease development in the future. Moreover, they may become a potential target for future therapeutic interventions for clinical disorders in diabetes.

Epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes.

PubMed

Khan, Fazlullah; Momtaz, Saeideh; Niaz, Kamal; Hassan, Fatima Ismail; Abdollahi, Mohammad

2017-09-01

Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance. This article reviewed epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes. Electronic databases such as PubMed, Scopus and Google scholar were searched for published literature from 1980 to 2017. Searched MESH terms were "Arsenic", "Epigenetic mechanism", "DNA methylation", "Histone modifications" and "Diabetes". There are various factors involved in the pathogenesis of T2DM but it is assumed that arsenic consumption causes the epigenetic alterations both at the gene-specific level and generalized genome level. The research indicates that exposure from low to moderate concentrations of iAs is linked with the epigenetic effects. In addition, it is evident that, arsenic can change the components of the epigenome and hence induces diabetes through epigenetic mechanisms, such as alterations in glucose transport and/or metabolism and insulin expression/secretion. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics

PubMed Central

Link, Alexander; Balaguer, Francesc; Goel, Ajay

2010-01-01

Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. PMID:20599773

Modifications to Axially Symmetric Simulations Using New DSMC (2007) Algorithms

NASA Technical Reports Server (NTRS)

Liechty, Derek S.

2008-01-01

Several modifications aimed at improving physical accuracy are proposed for solving axially symmetric problems building on the DSMC (2007) algorithms introduced by Bird. Originally developed to solve nonequilibrium, rarefied flows, the DSMC method is now regularly used to solve complex problems over a wide range of Knudsen numbers. These new algorithms include features such as nearest neighbor collisions excluding the previous collision partners, separate collision and sampling cells, automatically adaptive variable time steps, a modified no-time counter procedure for collisions, and discontinuous and event-driven physical processes. Axially symmetric solutions require radial weighting for the simulated molecules since the molecules near the axis represent fewer real molecules than those farther away from the axis due to the difference in volume of the cells. In the present methodology, these radial weighting factors are continuous, linear functions that vary with the radial position of each simulated molecule. It is shown that how one defines the number of tentative collisions greatly influences the mean collision time near the axis. The method by which the grid is treated for axially symmetric problems also plays an important role near the axis, especially for scalar pressure. A new method to treat how the molecules are traced through the grid is proposed to alleviate the decrease in scalar pressure at the axis near the surface. Also, a modification to the duplication buffer is proposed to vary the duplicated molecular velocities while retaining the molecular kinetic energy and axially symmetric nature of the problem.

Accommodations and Modifications: What Parents Need To Know = Facilidades y modificaciones: Lo que los padres necesitan saber.

ERIC Educational Resources Information Center

Beech, Marty

This English-Spanish language booklet is designed to help parents understand two important features of special education services, accommodations and modifications for students with disabilities. Examples of accommodations and modifications are provided, federal laws requiring schools to provide accommodations and modifications are cited, and…

Scalable imprinting of shape-specific polymeric nanocarriers using a release layer of switchable water solubility.

PubMed

Agarwal, Rachit; Singh, Vikramjit; Jurney, Patrick; Shi, Li; Sreenivasan, S V; Roy, Krishnendu

2012-03-27

There is increasing interest in fabricating shape-specific polymeric nano- and microparticles for efficient delivery of drugs and imaging agents. The size and shape of these particles could significantly influence their transport properties and play an important role in in vivo biodistribution, targeting, and cellular uptake. Nanoimprint lithography methods, such as jet-and-flash imprint lithography (J-FIL), provide versatile top-down processes to fabricate shape-specific, biocompatible nanoscale hydrogels that can deliver therapeutic and diagnostic molecules in response to disease-specific cues. However, the key challenges in top-down fabrication of such nanocarriers are scalable imprinting with biological and biocompatible materials, ease of particle-surface modification using both aqueous and organic chemistry as well as simple yet biocompatible harvesting. Here we report that a biopolymer-based sacrificial release layer in combination with improved nanocarrier-material formulation can address these challenges. The sacrificial layer improves scalability and ease of imprint-surface modification due to its switchable solubility through simple ion exchange between monovalent and divalent cations. This process enables large-scale bionanoimprinting and efficient, one-step harvesting of hydrogel nanoparticles in both water- and organic-based imprint solutions. © 2012 American Chemical Society

Microbiota and metabolic diseases.

PubMed

Pascale, Alessia; Marchesi, Nicoletta; Marelli, Cristina; Coppola, Adriana; Luzi, Livio; Govoni, Stefano; Giustina, Andrea; Gazzaruso, Carmine

2018-05-02

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus.

PubMed

Hartmann-Fatu, Cristina; Trusch, Franziska; Moll, Carina N; Michin, Irina; Hassinen, Antti; Kellokumpu, Sakari; Bayer, Peter

2015-03-27

Tyrosine sulfation of proteins is an important post-translational modification shown to play a role in many membrane-associated or extracellular processes such as virus entry, blood clotting, antibody-mediated immune response, inflammation and egg fecundation. The sole two human enzymes that transfer sulfate moieties from 3'-phospho-adenosine-5'-phospho-sulfate onto tyrosine residues, TPST1 and TPST2, are anchored to the membranes of the trans-Golgi compartment with the catalytic domain oriented to the lumen. In contrast to the relatively well studied organization of medial Golgi enzymes, the organization of trans-Golgi transferases remains elusive. Although tyrosylprotein sulfotransferases are known to exist as homodimers in the Golgi membranes, this organization level may represent only a small piece of a puzzle that is linked to the entire picture. Here we report the formation of TPST1/TPST2 heterodimers and a novel interaction between either TPST1 or TPST2 and the α-2,6-sialyltransferase, indicating a higher organization level of tyrosylprotein sulfotransferases that may serve for substrate selectivity and/or effective organization of multiple post-translational modification of proteins. Copyright © 2015. Published by Elsevier Ltd.

Proteomic analysis of post translational modifications in cyanobacteria.

PubMed

Xiong, Qian; Chen, Zhuo; Ge, Feng

2016-02-16

Cyanobacteria are a diverse group of Gram-negative bacteria and the only prokaryotes capable of oxygenic photosynthesis. Recently, cyanobacteria have attracted great interest due to their crucial roles in global carbon and nitrogen cycles and their ability to produce clean and renewable biofuels. To survive in various environmental conditions, cyanobacteria have developed a complex signal transduction network to sense environmental signals and implement adaptive changes. The post-translational modifications (PTMs) systems play important regulatory roles in the signaling networks of cyanobacteria. The systematic investigation of PTMs could contribute to the comprehensive description of protein species and to elucidate potential biological roles of each protein species in cyanobacteria. Although the proteomic studies of PTMs carried out in cyanobacteria were limited, these data have provided clues to elucidate their sophisticated sensing mechanisms that contribute to their evolutionary and ecological success. This review aims to summarize the current status of PTM studies and recent publications regarding PTM proteomics in cyanobacteria, and discuss the novel developments and applications for the analysis of PTMs in cyanobacteria. Challenges, opportunities and future perspectives in the proteomics studies of PTMs in cyanobacteria are also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration.

PubMed

Butterfield, D Allan; Hardas, Sarita S; Lange, Miranda L Bader

2010-01-01

Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc., that play important roles in normal and pathologic cell function. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the amyloid-beta protein precursor (AbetaPP). Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer's disease (AD) brain due to oxidative modification. Although oxidative stress and damage is a common phenomenon in the AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. In this review, we examine the many functions of GAPDH with respect to AD brain; in particular, the apparent role(s) of GAPDH in AD-related apoptotic cell death is emphasized.

A descriptive study of adherence to lifestyle modificationfactors among hypertensive patients.

PubMed

Alhalaiqa, Fadwa; Al-Nawafleh, Ahmad; Batiha, Abdul-Monim; Masa'deh, Rami; Abd Al-Razek, Aida

2017-02-27

Healthy life style recommendations (e.g., physical activity, healthy diet, and decreased cholesterol levels) play an important role in controlling blood pressure (BP). This study aimed to assess lifestyle modification factors among patients diagnosed with hypertension. A descriptive-survey design was used. Data were collected using four questionnaires; one was the Beliefs about Medication questionnaire (BMQ) and the rest were developed to collect data about demographic and clinical characteristics and lifestyle modification factors. In total 312 questionnaires were completed. The results revealed that our participants did not follow the healthy lifestyle recommendations; for example, the mean blood sugar (BS) level, body mass index (BMI), and cholesterol levels were 155 mg/dL (standard deviation (SD) = 71.9), 29 kg/m2 (SD = 5.4), and 197 mg/dL (SD = 86.6), respectively. A significant correlation was shown between age and BP (P = 0.000). Increase in diastolic BP (DBP) correlated with a significant increase in cholesterol level (P = 0.002) and BMI (P = 0.006). Our study showed that somewhat hypertensive patients in Jordan did not follow a healthy lifestyle. Therefore, urgent action by addressing behavioral risk factors has a positive impact on preventing and controlling hypertension.

Thermal treatment induced modification of structural, surface and bulk magnetic properties of Fe61.5Co5Ni8Si13.5B9Nb3 metallic glass

NASA Astrophysics Data System (ADS)

Shah, M.; Satalkar, M.; Kane, S. N.; Ghodke, N. L.; Sinha, A. K.; Varga, L. K.; Teixeira, J. M.; Araujo, J. P.

2018-05-01

Effect of thermal annealing induced modification of structural, surface and bulk magnetic properties of Fe61.5Co5Ni8Si13.5B9Nb3 alloy is presented. The changes in properties were observed using synchrotron x-ray diffraction technique (SXRD), atomic force microscopy (AFM), magneto-optical kerr effect (MOKE) and bulk magnetic measurements. Significant variations on the both side of surface occur for the annealing temperature upto 500 °C promotes the surface crystallization. Surface roughness appears due to presence of nanocrystallization plays an important role in determining magnetic properties. Observed lower value of bulk coercivity Hc of 6.2 A/m annealed temperature at 450 °C/1 h ascribed to reduction of disorder as compared to the surface (both shiny and wheel side observed by MOKE measurement) whereas improvement of bulk saturation magnetization with annealing temperature indicates first near neighbor shell of Fe atoms are surrounded by Fe atoms. Evolution of coercivity of surface and bulk with annealing temperature has been presented in conjunction with the structural observations.

Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention.

PubMed

Shukla, Samriddhi; Meeran, Syed M; Katiyar, Santosh K

2014-12-01

The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention

PubMed Central

Shukla, Samriddhi; Meeran, Syed M.; Katiyar, Santosh K.

2014-01-01

The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy. PMID:25236912

Nitroimidazoles adsorption on activated carbon cloth from aqueous solution.

PubMed

Ocampo-Pérez, R; Orellana-Garcia, F; Sánchez-Polo, M; Rivera-Utrilla, J; Velo-Gala, I; López-Ramón, M V; Alvarez-Merino, M A

2013-07-01

The objective of this study was to analyze the equilibrium and adsorption kinetics of nitroimidazoles on activated carbon cloth (ACC), determining the main interactions responsible for the adsorption process and the diffusion mechanism of these compounds on this material. The influence of the different operational variables, such as ionic strength, pH, temperature, and type of water (ultrapure, surface, and waste), was also studied. The results obtained show that the ACC has a high capacity to adsorb nitroimidazoles in aqueous solution. Electrostatic interactions play an important role at pH<3, which favors the repulsive forces between dimetridazole or metronidazole and the ACC surface. The formation of hydrogen bonds and dispersive interactions play the predominant role at higher pH values. Modifications of the ACC with NH3, K2S2O8, and O3 demonstrated that its surface chemistry plays a predominant role in nitroimidazole adsorption on this material. The adsorption capacity of ACC is considerably high in surface waters and reduced in urban wastewater, due to the levels of alkalinity and dissolved organic matter present in the different types of water. Finally, the results of applying kinetic models revealed that the global adsorption rate of dimetridazole and metronidazole is controlled by intraparticle diffusion. Copyright © 2013 Elsevier Inc. All rights reserved.

Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis.

PubMed

Bocheva, Georgeta; Boyadjieva, Nadka

2011-12-01

Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis.

Expansion of Protein Farnesyltransferase Specificity Using “Tunable” Active Site Interactions

PubMed Central

Hougland, James L.; Gangopadhyay, Soumyashree A.; Fierke, Carol A.

2012-01-01

Post-translational modifications play essential roles in regulating protein structure and function. Protein farnesyltransferase (FTase) catalyzes the biologically relevant lipidation of up to several hundred cellular proteins. Site-directed mutagenesis of FTase coupled with peptide selectivity measurements demonstrates that molecular recognition is determined by a combination of multiple interactions. Targeted randomization of these interactions yields FTase variants with altered and, in some cases, bio-orthogonal selectivity. We demonstrate that FTase specificity can be “tuned” using a small number of active site contacts that play essential roles in discriminating against non-substrates in the wild-type enzyme. This tunable selectivity extends in vivo, with FTase variants enabling the creation of bioengineered parallel prenylation pathways with altered substrate selectivity within a cell. Engineered FTase variants provide a novel avenue for probing both the selectivity of prenylation pathway enzymes and the effects of prenylation pathway modifications on the cellular function of a protein. PMID:22992747

An integrative review of attention biases and their contribution to treatment for anxiety disorders

PubMed Central

Barry, Tom J.; Vervliet, Bram; Hermans, Dirk

2015-01-01

Models of exposure therapy, one of the key components of cognitive behavioral therapy for anxiety disorders, suggest that attention may play an important role in the extinction of fear and anxiety. Evidence from cognitive research suggests that individual differences may play a causal role in the onset and maintenance of anxiety disorders and so it is also likely to influence treatment. We review the evidence concerning attention and treatment outcomes in anxiety disorders. The evidence reviewed here suggests that that attention biases assessed at pre-treatment might actually predict improved response to treatment, and in particular that prolonged engagement with threat as measured in tasks such as the dot probe is associated with greater reductions in anxious symptoms following treatment. We examine this research within a fear learning framework, considering the possible role of individual differences in attention in the extinction of fear during exposure. Theoretical, experimental and clinical implications are discussed, particularly with reference to the potential for attention bias modification programs in augmenting treatment, and also with reference to how existing research in this area might inform best practice for clinicians. PMID:26217284

Modified Active Videogame Play Results in Moderate-Intensity Exercise.

PubMed

Monedero, Javier; McDonnell, Adam C; Keoghan, Melissa; O'Gorman, Donal J

2014-08-01

Large proportions of the population do not meet current American College of Sports Medicine physical activity recommendations, and innovative approaches are required. Most active videogames do not require a significant amount of energy expenditure. The purpose of this study was to determine if modifying an active videogame increased exercise intensity to meet current physical activity recommendations. After completing a maximal oxygen uptake test, participants did a familiarization session on a separate day. Thirteen healthy participants 24.2±3.4 years of age played (1) a sedentary videogame, (2) an active videogame, and (3) a modified active videogame designed to increase physical activity for 46 minutes in a randomized order on separate days. Oxygen uptake, heart rate, heart rate reserve, percentage of maximal heart rate, metabolic equivalents of task, and energy expenditure were significantly higher during the modified active videogame trial than during the active videogame or sedentary videogame trials and also between the active videogame and sedentary videogame. A simple modification to an existing active videogame was sufficient to reach moderate exercise intensity. Active videogames could provide an important option for increasing daily physical activity and reducing sedentary time.

Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.

PubMed

Manickam, Nandini; Joshi, Kartikeya; Bhatt, Monika J; Farabaugh, Philip J

2016-02-29

Cellular health and growth requires protein synthesis to be both efficient to ensure sufficient production, and accurate to avoid producing defective or unstable proteins. The background of misreading error frequency by individual tRNAs is as low as 2 × 10(-6) per codon but is codon-specific with some error frequencies above 10(-3) per codon. Here we test the effect on error frequency of blocking post-transcriptional modifications of the anticodon loops of four tRNAs in Escherichia coli. We find two types of responses to removing modification. Blocking modification of tRNA(UUC)(Glu) and tRNA(QUC)(Asp) increases errors, suggesting that the modifications act at least in part to maintain accuracy. Blocking even identical modifications of tRNA(UUU)(Lys) and tRNA(QUA)(Tyr) has the opposite effect of decreasing errors. One explanation could be that the modifications play opposite roles in modulating misreading by the two classes of tRNAs. Given available evidence that modifications help preorder the anticodon to allow it to recognize the codons, however, the simpler explanation is that unmodified 'weak' tRNAs decode too inefficiently to compete against cognate tRNAs that normally decode target codons, which would reduce the frequency of misreading. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The rational parameterization theorem for multisite post-translational modification systems.

PubMed

Thomson, Matthew; Gunawardena, Jeremy

2009-12-21

Post-translational modification of proteins plays a central role in cellular regulation but its study has been hampered by the exponential increase in substrate modification forms ("modforms") with increasing numbers of sites. We consider here biochemical networks arising from post-translational modification under mass-action kinetics, allowing for multiple substrates, having different types of modification (phosphorylation, methylation, acetylation, etc.) on multiple sites, acted upon by multiple forward and reverse enzymes (in total number L), using general enzymatic mechanisms. These assumptions are substantially more general than in previous studies. We show that the steady-state modform concentrations constitute an algebraic variety that can be parameterized by rational functions of the L free enzyme concentrations, with coefficients which are rational functions of the rate constants. The parameterization allows steady states to be calculated by solving L algebraic equations, a dramatic reduction compared to simulating an exponentially large number of differential equations. This complexity collapse enables analysis in contexts that were previously intractable and leads to biological predictions that we review. Our results lay a foundation for the systems biology of post-translational modification and suggest deeper connections between biochemical networks and algebraic geometry.

The impact of teachers’ modifications of an evidenced-based HIV prevention intervention on program outcomes

PubMed Central

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2015-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade six students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers’ modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25% or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers’ level of implementation. We conclude that poorer student outcomes were associated with heavy modifications. PMID:26297497

The Impact of Teachers' Modifications of an Evidenced-Based HIV Prevention Intervention on Program Outcomes.

PubMed

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2016-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade 6 students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers' modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25 % or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, and shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers' level of implementation. We conclude that poorer student outcomes were associated with heavy modifications.

Epigenetic modification of the oxytocin receptor gene influences the perception of anger and fear in the human brain

PubMed Central

Puglia, Meghan H.; Lillard, Travis S.; Morris, James P.; Connelly, Jessica J.

2015-01-01

In humans, the neuropeptide oxytocin plays a critical role in social and emotional behavior. The actions of this molecule are dependent on a protein that acts as its receptor, which is encoded by the oxytocin receptor gene (OXTR). DNA methylation of OXTR, an epigenetic modification, directly influences gene transcription and is variable in humans. However, the impact of this variability on specific social behaviors is unknown. We hypothesized that variability in OXTR methylation impacts social perceptual processes often linked with oxytocin, such as perception of facial emotions. Using an imaging epigenetic approach, we established a relationship between OXTR methylation and neural activity in response to emotional face processing. Specifically, high levels of OXTR methylation were associated with greater amounts of activity in regions associated with face and emotion processing including amygdala, fusiform, and insula. Importantly, we found that these higher levels of OXTR methylation were also associated with decreased functional coupling of amygdala with regions involved in affect appraisal and emotion regulation. These data indicate that the human endogenous oxytocin system is involved in attenuation of the fear response, corroborating research implicating intranasal oxytocin in the same processes. Our findings highlight the importance of including epigenetic mechanisms in the description of the endogenous oxytocin system and further support a central role for oxytocin in social cognition. This approach linking epigenetic variability with neural endophenotypes may broadly explain individual differences in phenotype including susceptibility or resilience to disease. PMID:25675509

EZH2 regulates neuroblastoma cell differentiation via NTRK1 promoter epigenetic modifications.

PubMed

Li, Zhenghao; Takenobu, Hisanori; Setyawati, Amallia Nuggetsiana; Akita, Nobuhiro; Haruta, Masayuki; Satoh, Shunpei; Shinno, Yoshitaka; Chikaraishi, Koji; Mukae, Kyosuke; Akter, Jesmin; Sugino, Ryuichi P; Nakazawa, Atsuko; Nakagawara, Akira; Aburatani, Hiroyuki; Ohira, Miki; Kamijo, Takehiko

2018-05-01

The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported. A Kaplan-Meier analysis on the event free survival and overall survival of NB patients indicated that the high expression of EZH2 correlated with an unfavorable prognosis. In order to elucidate the functional roles of EZH2 in NB tumorigenesis and its aggressiveness, we knocked down EZH2 in NB cell lines using lentivirus systems. The knockdown of EZH2 significantly induced NB cell differentiation, e.g., neurite extension, and the neuronal differentiation markers, NF68 and GAP43. EZH2 inhibitors also induced NB cell differentiation. We performed a comprehensive transcriptome analysis using Human Gene Expression Microarrays and found that NTRK1 (TrkA) is one of the EZH2-related suppression targets. The depletion of NTRK1 canceled EZH2 knockdown-induced NB cell differentiation. Our integrative methylome, transcriptome, and chromatin immunoprecipitation assays using NB cell lines and clinical samples clarified that the NTRK1 P1 and P2 promoter regions were regulated differently by DNA methylation and EZH2-related histone modifications. The NTRK1 transcript variants 1/2, which were regulated by EZH2-related H3K27me3 modifications at the P1 promoter region, were strongly expressed in favorable, but not unfavorable NB. The depletion and inhibition of EZH2 successfully induced NTRK1 transcripts and functional proteins. Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.

Effectiveness of two different behavioral modification techniques among 5-7-year-old children: A randomized controlled trial.

PubMed

Vishwakarma, Aruna Prashanth; Bondarde, Prashant Arjun; Patil, Sudha Bhimangouda; Dodamani, Arun Suresh; Vishwakarma, Prashanth Yachrappa; Mujawar, Shoeb A

2017-01-01

Dental fear is a common, essential, and inevitable emotion that appears as a response to the stressful situation, which raises children's anxiety level, resulting in reduced demand for pediatric dental care. (1) To compare and evaluate the effectiveness of customized tell-play-do (TPD) technique with live modeling for behavior management of children. (2) To compare the behavioral modification techniques in managing the children during their dental visits. Ninety-eight children aged 5-7 years were enrolled in the study and randomly allocated into two groups. Phase I: first visit. Group I - children were conditioned to receive various dental procedures using live modeling followed by oral prophylaxis. Group II - TPD technique was introduced with customized playing dental objects followed by oral prophylaxis. Phase II: second visit. After 7 days interval, all the study subjects were subjected to rotary restorative treatment. Heart rate, Facial Image Scale (FIS), and Venham-6-point index were used before intervention, after intervention, and during dental procedure to quantify the anxious behavior. All 98 children after intervention underwent oral prophylaxis on first visit and rotary restorative treatment on second visit. The average pulse rate, FIS, and Venham scale scores were significantly lower among children who received TPD intervention when compared to those who received live modeling intervention. Unpaired t-test at 5% level of significance was considered as statistical significance. TPD is effective in reducing children's fear and anxiety about dental treatment, children enjoy playing with customized dental object. Thus, to promote adaptive behavior, TPD could be an alternate behavioral modification technique during pediatric dentistry.

Recombinant entomopathogenic agents: a review of biotechnological approaches to pest insect control.

PubMed

Karabörklü, Salih; Azizoglu, Ugur; Azizoglu, Zehra Busra

2017-12-18

Although the use of chemical pesticides has decreased in recent years, it is still a common method of pest control. However, chemical use leads to challenging problems. The harm caused by these chemicals and the length of time that they will remain in the environment is of great concern to the future and safety of humans. Therefore, developing new pest control agents that are safer and environmentally compatible, as well as assuring their widespread use is important. Entomopathogenic agents are microorganisms that play an important role in the biological control of pest insects and are eco-friendly alternatives to chemical control. They consist of viruses (non-cellular organisms), bacteria (prokaryotic organisms), fungi and protists (eukaryotic organisms), and nematodes (multicellular organisms). Genetic modification (recombinant technology) provides potential new methods for developing entomopathogens to manage pests. In this review, we focus on the important roles of recombinant entomopathogens in terms of pest insect control, placing them into perspective with other views to discuss, examine and evaluate the use of entomopathogenic agents in biological control.

Histone H3 K79 methylation states play distinct roles in UV-induced sister chromatid exchange and cell cycle checkpoint arrest in Saccharomyces cerevisiae

PubMed Central

Rossodivita, Alyssa A.; Boudoures, Anna L.; Mecoli, Jonathan P.; Steenkiste, Elizabeth M.; Karl, Andrea L.; Vines, Eudora M.; Cole, Arron M.; Ansbro, Megan R.; Thompson, Jeffrey S.

2014-01-01

Histone post-translational modifications have been shown to contribute to DNA damage repair. Prior studies have suggested that specific H3K79 methylation states play distinct roles in the response to UV-induced DNA damage. To evaluate these observations, we examined the effect of altered H3K79 methylation patterns on UV-induced G1/S checkpoint response and sister chromatid exchange (SCE). We found that the di- and trimethylated states both contribute to activation of the G1/S checkpoint to varying degrees, depending on the synchronization method, although methylation is not required for checkpoint in response to high levels of UV damage. In contrast, UV-induced SCE is largely a product of the trimethylated state, which influences the usage of gene conversion versus popout mechanisms. Regulation of H3K79 methylation by H2BK123 ubiquitylation is important for both checkpoint function and SCE. H3K79 methylation is not required for the repair of double-stranded breaks caused by transient HO endonuclease expression, but does play a modest role in survival from continuous exposure. The overall results provide evidence for the participation of H3K79 methylation in UV-induced recombination repair and checkpoint activation, and further indicate that the di- and trimethylation states play distinct roles in these DNA damage response pathways. PMID:24748660

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport.

PubMed

Rocher, Françoise; Roblin, Gabriel; Chollet, Jean-François

2017-03-01

Early prediction of compound absorption by cells is of considerable importance in the building of an integrated scheme describing the impact of a compound on intracellular biological processes. In this scope, we study the structure-activity relationships of several benzoic acid-related phenolics which are involved in many plant biological phenomena (growth, flowering, allelopathy, defense processes). Using the partial least squares (PLS) regression method, the impact of molecular descriptors that have been shown to play an important role concerning the uptake of pharmacologically active compounds by animal cells was analyzed in terms of the modification of membrane potential, variations in proton flux, and inhibition of the osmocontractile reaction of pulvinar cells of Mimosa pudica leaves. The hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA), polar surface area (PSA), halogen ratio (Hal ratio), number of rotatable bonds (FRB), molar volume (MV), molecular weight (MW), and molar refractivity (MR) were considered in addition to two physicochemical properties (logD and the amount of non-dissociated form in relation to pKa). HBD + HBA and PSA predominantly impacted the three biological processes compared to the other descriptors. The coefficient of determination in the quantitative structure-activity relationship (QSAR) models indicated that a major part of the observed seismonasty inhibition and proton flux modification can be explained by the impact of these descriptors, whereas this was not the case for membrane potential variations. These results indicate that the transmembrane transport of the compounds is a predominant component. An increasing number of implicated descriptors as the biological processes become more complex may reflect their impacts on an increasing number of sites in the cell. The determination of the most efficient effectors may lead to a practical use to improve drugs in the control of microbial attacks on plants.

The Unexpected and Exceptionally Facile Chemical Modification of the Phenolic Hydroxyl Group of Tyrosine by Polyhalogenated Quinones under Physiological Conditions.

PubMed

Qu, Na; Li, Feng; Shao, Bo; Shao, Jie; Zhai, Guijin; Wang, Fuyi; Zhu, Ben-Zhan

2016-10-17

The phenolic hydroxyl group of tyrosine residue plays a crucial role in the structure and function of many proteins. However, little study has been reported about its modification by chemical agents under physiological conditions. In this study, we found, unexpectedly, that the phenolic hydroxyl group of tyrosine can be rapidly and efficiently modified by tetrafluoro-1,4-benzoquinone and other polyhalogenated quinones, which are the major genotoxic and carcinogenic quinoid metabolites of polyhalogenated aromatic compounds. The modification was found to be mainly due to the formation of a variety of fluoroquinone-O-tyrosine conjugates and their hydroxylated derivatives via nucleophilic substitution pathway. Analogous modifications were observed for tyrosine-containing peptides. Further studies showed that the blockade of the reactive phenolic hydroxyl group of tyrosine in the substrate peptide, even by very low concentration of tetrafluoro-1,4-benzoquinone, can prevent the kinase catalyzed tyrosine phosphorylation. This is the first report showing the exceptionally facile chemical modification of the phenolic hydroxyl group of tyrosine by polyhalogenated quinones under normal physiological conditions, which may have potential biological and toxicological implications.

Optimized methods of chromatin immunoprecipitation for profiling histone modifications in industrial microalgae Nannochloropsis spp.

PubMed

Wei, Li; Xu, Jian

2018-06-01

Epigenetic factors such as histone modifications play integral roles in plant development and stress response, yet their implications in algae remain poorly understood. In the industrial oleaginous microalgae Nannochloropsis spp., the lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which determines the specific genomic location of various histone modifications, has hindered probing the epigenetic basis of their photosynthetic carbon conversion and storage as oil. Here, a detailed ChIP protocol was developed for Nannochloropsis oceanica, which represents a reliable approach for the analysis of histone modifications, chromatin state, and transcription factor-binding sites at the epigenetic level. Using ChIP-qPCR, genes related to photosynthetic carbon fixation in this microalga were systematically assessed. Furthermore, a ChIP-Seq protocol was established and optimized, which generated a genome-wide profile of histone modification events, using histone mark H3K9Ac as an example. These results are the first step for appreciation of the chromatin landscape in industrial oleaginous microalgae and for epigenetics-based microalgal feedstock development. © 2018 Phycological Society of America.

Chemically Derivatized Semiconductor Photoelectrodes.

ERIC Educational Resources Information Center

Wrighton, Mark S.

1983-01-01

Deliberate modification of semiconductor photoelectrodes to improve durability and enhance rate of desirable interfacial redox processes is discussed for a variety of systems. Modification with molecular-based systems or with metals/metal oxides yields results indicating an important role for surface modification in devices for fundamental study…

Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage.

PubMed

Pascual, María; Baliño, Pablo; Alfonso-Loeches, Silvia; Aragón, Carlos M G; Guerri, Consuelo

2011-06-01

Toll-like receptors (TLRs) play an important role in the innate immune response, and emerging evidence indicates their role in brain injury and neurodegeneration. Our recent results have demonstrated that ethanol is capable of activating glial TLR4 receptors and that the elimination of these receptors in mice protects against ethanol-induced glial activation, induction of inflammatory mediators and apoptosis. This study was designed to assess whether ethanol-induced inflammatory damage causes behavioral and cognitive consequences, and if behavioral alterations are dependent of TLR4 functions. Here we show in mice drinking alcohol for 5months, followed by a 15-day withdrawal period, that activation of the astroglial and microglial cells in frontal cortex and striatum is maintained and that these events are associated with cognitive and anxiety-related behavioral impairments in wild-type (WT) mice, as demonstrated by testing the animals with object memory recognition, conditioned taste aversion and dark and light box anxiety tasks. Mice lacking TLR4 receptors are protected against ethanol-induced inflammatory damage, and behavioral associated effects. We further assess the possibility of the epigenetic modifications participating in short- or long-term behavioral effects associated with neuroinflammatory damage. We show that chronic alcohol treatment decreases H4 histone acetylation and histone acetyltransferases activity in frontal cortex, striatum and hippocampus of WT mice. Alterations in chromatin structure were not observed in TLR4(-/-) mice. These results provide the first evidence of the role that TLR4 functions play in the behavioral consequences of alcohol-induced inflammatory damage and suggest that the epigenetic modifications mediated by TLR4 could contribute to short- or long-term alcohol-induced behavioral or cognitive dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Chitosan-based coatings in the prevention of intravascular catheter-associated infections.

PubMed

Mendoza, Gracia; Regiel-Futyra, Anna; Tamayo, Alejandra; Monzon, Marta; Irusta, Silvia; de Gregorio, Miguel Angel; Kyzioł, Agnieszka; Arruebo, Manuel

2018-01-01

Central venous access devices play an important role in patients with prolonged intravenous administration requirements. In the last years, the coating of these devices with bactericidal compounds has emerged as a potential tool to prevent bacterial colonization. Our study describes the modification of 3D-printed reservoirs and silicone-based catheters, mimicking central venous access devices, through different approaches including their coating with the well known biocompatible and bactericidal polymer chitosan, with the anionic polysaccharide alginate; also, plasma treated surfaces were included in the study to promote polymer adhesion. The evaluation of the antimicrobial action of those surface modifications compared to that exerted by a model antibiotic (ciprofloxacin) adsorbed on the surface of the devices was carried out. Surface characterization was developed by different methodologies and the bactericidal effects of the different coatings were assayed in an in vitro model of Staphylococcus aureus infection. Our results showed a significant reduction in the reservoir roughness (≤73%) after coating though no changes were observed for coated catheters which was also confirmed by scanning electron microscopy, pointing to the importance of the surface device topography for the successful attachment of the coating and for the subsequent development of bactericidal effects. Furthermore, the single presence of chitosan on the reservoirs was enough to fully inhibit bacterial growth exerting the same efficiency as that showed by the model antibiotic. Importantly, chitosan coating showed low cytotoxicity against human keratinocytes, human lung adenocarcinoma epithelial cells, and murine colon carcinoma cells displaying viability percentages in the range of the control samples (>95%). Chitosan-based coatings are proposed as an effective and promising solution in the prevention of microbial infections associated to medical devices.

Self-Assembled Carbon-Polyoxometalate Composites for Electrochemical Capacitors

NASA Astrophysics Data System (ADS)

Genovese, Matthew

The development of high performance yet cost effective energy storage devices is critical for enabling the growth of important emerging sectors from the internet of things to grid integration of renewable energy. Material costs are by far the largest contributor to the overall cost of energy storage devices and thus research into cost effective energy storage materials will play an important role in developing technology to meet real world storage demands. In this thesis, low cost high performance composite electrode materials for supercapacitors (SCs) have been developed through the surface modification of electrochemically double layer capacitive (EDLC) carbon substrates with pseudocapacitive Polyoxometalates (POMs). Significant fundamental contributions have been made to the understanding of all components of the composite electrode including the POM active layer, cation linker, and carbon substrate. The interaction of different POM chemistries in solution has been studied to elucidate the novel ways in which these molecules combine and the mechanism underlying this combination. A more thorough understanding regarding the cation linker's role in electrode fabrication has been developed through examining the linker properties which most strongly affect electrode performance. The development of porosity in biomass derived carbon materials has also been examined leading to important insights regarding the effect of substrate porosity on POM modification and electrochemical properties. These fundamental contributions enabled the design and performance optimization of POM-carbon composite SC electrodes. Understanding how POMs combine in solution, allowed for the development of mixed POM molecular coatings with tunable electrochemical properties. These molecular coatings were used to modify low cost biomass derived carbon substrates that had been structurally optimized to accommodate POM molecules. The resulting electrode composites utilizing low cost materials fabricated through simple scalable techniques demonstrated (i) high capacitance (361 F g-1), (ii) close to ideal pseudocapacitive behavior, (iii) stable cycling, and (iv) good rate performance.

Comparative Monomethylarginine Proteomics Suggests that Protein Arginine Methyltransferase 1 (PRMT1) is a Significant Contributor to Arginine Monomethylation in Toxoplasma gondii

PubMed Central

Yakubu, Rama R.; Silmon de Monerri, Natalie C.; Nieves, Edward; Kim, Kami; Weiss, Louis M.

2017-01-01

Arginine methylation is a common posttranslational modification found on nuclear and cytoplasmic proteins that has roles in transcriptional regulation, RNA metabolism and DNA repair. The protozoan parasite Toxoplasma gondii has a complex life cycle requiring transcriptional plasticity and has unique transcriptional regulatory pathways. Arginine methylation may play an important part in transcriptional regulation and splicing biology in this organism. The T. gondii genome contains five putative protein arginine methyltransferases (PRMTs), of which PRMT1 is important for cell division and growth. In order to better understand the function(s) of the posttranslational modification monomethyl arginine (MMA) in T. gondii, we performed a proteomic analysis of MMA proteins using affinity purification employing anti-MMA specific antibodies followed by mass spectrometry. The arginine monomethylome of T. gondii contains a large number of RNA binding proteins and multiple ApiAP2 transcription factors, suggesting a role for arginine methylation in RNA biology and transcriptional regulation. Surprisingly, 90% of proteins that are arginine monomethylated were detected as being phosphorylated in a previous phosphoproteomics study which raises the possibility of interplay between MMA and phosphorylation in this organism. Supporting this, a number of kinases are also arginine methylated. Because PRMT1 is thought to be a major PRMT in T. gondii, an organism which lacks a MMA-specific PRMT, we applied comparative proteomics to understand how PRMT1 might contribute to the MMA proteome in T. gondii. We identified numerous putative PRMT1 substrates, which include RNA binding proteins, transcriptional regulators (e.g. AP2 transcription factors), and kinases. Together, these data highlight the importance of MMA and PRMT1 in arginine methylation in T. gondii, as a potential regulator of a large number of processes including RNA biology and transcription. PMID:28143887

Replication protein A, the laxative that keeps DNA regular: The importance of RPA phosphorylation in maintaining genome stability.

PubMed

Byrne, Brendan M; Oakley, Gregory G

2018-04-20

The eukaryotic ssDNA-binding protein, Replication protein A (RPA), was first discovered almost three decades ago. Since then, much progress has been made to elucidate the critical roles for RPA in DNA metabolic pathways that help promote genomic stability. The canonical RPA heterotrimer (RPA1-3) is an essential coordinator of DNA metabolism that interacts with ssDNA and numerous protein partners to coordinate its roles in DNA replication, repair, recombination and telomere maintenance. An alternative form of RPA, termed aRPA, is formed by a complex of RPA4 with RPA1 and RPA3. aRPA is expressed differentially in cells compared to canonical RPA and has been shown to inhibit canonical RPA function while allowing for regular maintenance of cell viability. Interestingly, while aRPA is defective in DNA replication and cell cycle progression, it was shown to play a supporting role in nucleotide excision repair and recombination. The binding domains of canonical RPA interact with a growing number of partners involved in numerous genome maintenance processes. The protein interactions of the RPA-ssDNA complex are not only governed by competition between the binding proteins but also by post-translation modifications such as phosphorylation. Phosphorylation of RPA2 is an important post-translational modification of the RPA complex, and is essential for directing context-specific functions of the RPA complex in the DNA damage response. Due to the importance of RPA in cellular metabolism, it was identified as an appealing target for chemotherapeutic drug development that could be used in future cancer treatment regimens. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fermentation Enhancement of Methanogenic Archaea Consortia from an Illinois Basin Coalbed via DOL Emulsion Nutrition

PubMed Central

Xiao, Dong; Peng, Su-Ping; Wang, En-Yuan

2015-01-01

Microbially enhanced coalbed methane technology must be used to increase the methane content in mining and generate secondary biogenic gas. In this technology, the metabolic processes of methanogenic consortia are the basis for the production of biomethane from some of the organic compounds in coal. Thus, culture nutrition plays an important role in remediating the nutritional deficiency of a coal seam. To enhance the methane production rates for microorganism consortia, different types of nutrition solutions were examined in this study. Emulsion nutrition solutions containing a novel nutritional supplement, called dystrophy optional modification latex, increased the methane yield for methanogenic consortia. This new nutritional supplement can help methanogenic consortia form an enhanced anaerobic environment, optimize the microbial balance in the consortia, and improve the methane biosynthesis rate. PMID:25884952

Grass flower development.

PubMed

Hirano, Hiro-Yuki; Tanaka, Wakana; Toriba, Taiyo

2014-01-01

Grasses bear unique flowers lacking obvious petals and sepals in special inflorescence units, the florets and the spikelet. Despite this, grass floral organs such as stamens and lodicules (petal homologs) are specified by ABC homeotic genes encoding MADS domain transcription factors, suggesting that the ABC model of eudicot flower development is largely applicable to grass flowers. However, some modifications need to be made for the model to fit grasses well: for example, a YABBY gene plays an important role in carpel specification. In addition, a number of genes are involved in the development of the lateral organs that constitute the spikelet. In this review, we discuss recent progress in elucidating the genes required for flower and spikelet development in grasses, together with those involved in fate determination of the spikelet and flower meristems.

TRIM Family Proteins: Roles in Autophagy, Immunity, and Carcinogenesis.

PubMed

Hatakeyama, Shigetsugu

2017-04-01

Tripartite motif (TRIM) family proteins, most of which have E3 ubiquitin ligase activities, have various functions in cellular processes including intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis. The ubiquitin system is one of the systems for post-translational modifications, which play crucial roles not only as markers for degradation of target proteins by the proteasome but also as regulators of protein-protein interactions and of the activation of enzymes. Accumulating evidence has shown that TRIM family proteins have unique, important roles and that their dysregulation causes several diseases classified as cancer, immunological disease, or developmental disorders. In this review we focus on recent emerging topics on TRIM proteins in the regulation of autophagy, innate immunity, and carcinogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patellofemoral pain in athletes: clinical perspectives

PubMed Central

Halabchi, Farzin; Abolhasani, Maryam; Mirshahi, Maryam; Alizadeh, Zahra

2017-01-01

Patellofemoral pain (PFP) is a very common problem in athletes who participate in jumping, cutting and pivoting sports. Several risk factors may play a part in the pathogenesis of PFP. Overuse, trauma and intrinsic risk factors are particularly important among athletes. Physical examination has a key role in PFP diagnosis. Furthermore, common risk factors should be investigated, such as hip muscle dysfunction, poor core muscle endurance, muscular tightness, excessive foot pronation and patellar malalignment. Imaging is seldom needed in special cases. Many possible interventions are recommended for PFP management. Due to the multifactorial nature of PFP, the clinical approach should be individualized, and the contribution of different factors should be considered and managed accordingly. In most cases, activity modification and rehabilitation should be tried before any surgical interventions. PMID:29070955

Proteomics for understanding miRNA biology.

PubMed

Huang, Tai-Chung; Pinto, Sneha M; Pandey, Akhilesh

2013-02-01

MicroRNAs (miRNAs) are small noncoding RNAs that play important roles in posttranscriptional regulation of gene expression. Mature miRNAs associate with the RNA interference silencing complex to repress mRNA translation and/or degrade mRNA transcripts. Mass spectrometry-based proteomics has enabled identification of several core components of the canonical miRNA processing pathway and their posttranslational modifications which are pivotal in miRNA regulatory mechanisms. The use of quantitative proteomic strategies has also emerged as a key technique for experimental identification of miRNA targets by allowing direct determination of proteins whose levels are altered because of translational suppression. This review focuses on the role of proteomics and labeling strategies to understand miRNA biology. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

H2A-DUBbing the mammalian epigenome: expanding frontiers for histone H2A deubiquitinating enzymes in cell biology and physiology.

PubMed

Belle, Jad I; Nijnik, Anastasia

2014-05-01

Posttranslational modifications of histone H2A through the attachment of ubiquitin or poly-ubiquitin conjugates are common in mammalian genomes and play an important role in the regulation of chromatin structure, gene expression, and DNA repair. Histone H2A deubiquitinases (H2A-DUBs) are a group of structurally diverse enzymes that catalyze the removal ubiquitin from histone H2A. In this review we provide a concise summary of the mechanisms that mediate histone H2A ubiquitination in mammalian cells, and review our current knowledge of mammalian H2A-DUBs, their biochemical activities, and recent developments in our understanding of their functions in mammalian physiology. Copyright © 2014 Elsevier Ltd. All rights reserved.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease.

PubMed

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(-)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(-), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk.

LDL electronegativity index: a potential novel index for predicting cardiovascular disease

PubMed Central

Ivanova, Ekaterina A; Bobryshev, Yuri V; Orekhov, Alexander N

2015-01-01

High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(–)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(–), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. PMID:26357481

Abnormalities of Lipoprotein Levels in Liver Cirrhosis: Clinical Relevance.

PubMed

Privitera, Graziella; Spadaro, Luisa; Marchisello, Simona; Fede, Giuseppe; Purrello, Francesco

2018-01-01

Progressive lipoprotein impairment occurs in liver cirrhosis and is associated with increased morbidity and mortality. The present review aims to summarize the current evidence regarding the prognostic value of lipoprotein abnormalities in liver cirrhosis and to address the need of a better prognostic stratification of patients, including lipoprotein profile assessment. Low levels of lipoproteins are usual in cirrhosis. Much evidence supports the prognostic role of hypolipidemia in cirrhotic patients. In particular, hypocholesterolemia represents an independent predictor of survival in cirrhosis. In cirrhotic patients, lipoprotein impairment is associated with several complications: infections, malnutrition, adrenal function, and spur cell anemia. Alterations of liver function are associated with modifications of circulating lipids. Decreased levels of lipoproteins significantly impact the survival of cirrhotic patients and play an important role in the pathogenesis of some cirrhosis-related complications.

Inhibitors of Protein Methyltransferases and Demethylases

PubMed Central

2017-01-01

Post-translational modifications of histones by protein methyltransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene expression and transcription and are implicated in cancer and many other diseases. Many of these enzymes also target various nonhistone proteins impacting numerous crucial biological pathways. Given their key biological functions and implications in human diseases, there has been a growing interest in assessing these enzymes as potential therapeutic targets. Consequently, discovering and developing inhibitors of these enzymes has become a very active and fast-growing research area over the past decade. In this review, we cover the discovery, characterization, and biological application of inhibitors of PMTs and KDMs with emphasis on key advancements in the field. We also discuss challenges, opportunities, and future directions in this emerging, exciting research field. PMID:28338320

Negative regulation of neuronal cell differentiation by INHAT subunit SET/TAF-Iβ.

PubMed

Kim, Dong-Wook; Kim, Kee-Beom; Kim, Ji-Young; Lee, Kyu-Sun; Seo, Sang-Beom

2010-09-24

Epigenetic modification plays an important role in transcriptional regulation. As a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF-Iβ evidences transcriptional repression activity. In this study, we demonstrate that SET/TAF-Iβ is abundantly expressed in neuronal tissues of Drosophila embryos. It is expressed at high levels prior to and in early stages of neuronal development, and gradually reduced as differentiation proceeds. SET/TAF-Iβ binds to the promoters of a subset of neuronal development markers and negatively regulates the transcription of these genes. The results of this study show that the knockdown of SET/TAF-Iβ by si-RNA induces neuronal cell differentiation, thus implicating SET/TAF-Iβ as a negative regulator of neuronal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Exercise-mediated changes in high-density lipoprotein: impact on form and function.

PubMed

Blazek, Alisa; Rutsky, Jessica; Osei, Kwame; Maiseyeu, Andrei; Rajagopalan, Sanjay

2013-09-01

The goal of this systematic review was to assess the current understanding of the effects of exercise intervention on high-density lipoprotein (HDL) cholesterol (HDL-C) and changes in HDL function as well as modification of these effects by genomic factors. The reviewed studies demonstrate that exercise has modest effects on HDL-C with limited data suggesting an effect on HDL function. Genetic polymorphisms in proteins associated with HDL metabolism play a role in modifying the HDL-C response to exercise and possibly its function. Exercise as an intervention for patients at risk for cardiovascular events can lead to small improvements in HDL-C and potential changes in HDL function. There is an important modifier effect of genetics in determining these changes. Copyright © 2013 Mosby, Inc. All rights reserved.

[Mechanisms of signaling associated with reactive nitrogen and oxygen in apoptosis].

PubMed

Piłat, Justyna; Ługowski, Mateusz; Saczko, Jolanta; Choromańska, Anna; Chwiłkowska, Agnieszka; Banaś, Teresa; Kulbacka, Julita

2016-05-01

The knowledge of apoptotic mechanisms is essential in many biologic aspects related to both normal and neoplastic cells. Cell death by apoptosis is a very desirable way to eliminate unwanted cells: prevents release of the cellular content, which, in contrast to necrosis, provides no activation of inflammatory reactions. Apoptosis is a multistep process in where an extremely important role is played by caspases. Functions of caspases and their modifications are fundamental to understanding the signaling pathways responsible for regulation of apoptosis. These enzymes belong to a family of cysteine proteases that have the potential to destroy the enzymatic and structural proteins, and in the final stages of apoptosis, to lead to the disintegration of the cell. Apoptosis can be modulated by certain signaling pathway. © 2016 MEDPRESS.

Re-connecting Urban Ecohydrology to Improve Ecosystem Functioning: The Role of Local-scale Green Infrastructure

NASA Astrophysics Data System (ADS)

Pavao-Zuckerman, M.

2010-12-01

As rates of urbanization continue to rise and a greater proportion of the population lives in urban and suburban areas, the provision of ecological services and functions become increasingly important to sustain human and environmental health in urban ecosystems. Soils play a primary role in the healthy functioning of ecosystems that provide supporting, provisioning, regulating, preserving, and cultural ecosystem services, yet developing our understanding of how urban soils function to provide these services within an ecological context is just getting underway. Soils in urban ecosytems are highly heterogeneous, and are affected by both direct and indirect influences and local modifications which alter their functioning relative to non-urbanized local soils. Here I discuss the functioning of rain gardens in and around Tucson, AZ, that have been installed in the urban landscape with the purpose of providing various ecosystem services to local residents and the greater urban ecosystem. This reconnection of ecohydrologic flows in the city has the potential to alter the structure and function of urban ecosystems in positive (through the increase in water availability) and negative (through the import of pollutants to soils) ways. This study compares soil properties, microbial function, and ecosystem functions within the urban ecosystem to determine how urbanization alters soils in semi-arid environments, and to determine if green urban modifications in desert cities can improve soils and ecosystem services. Soils in rain gardens have nearly twice the organic matter contents of native and urban soils, and correspondingly, greater microbial function (as indicated through respiration potential), higher abundance (through substrate induced respiration), and community complexity (indicated by a 3x increase in metabolic diversity) in these green design modifications. Net N-mineralization rates are almost 1.5 times faster in the rain garden basins than urban soils in general. This study also includes the comparison of different approaches to installing rain gardens to illustrate the effects of different management strategies on biogeochemical cycling. The inclusion of mulch in the garden design increases microbial biomass and reduces the rate of N-mineralization. These data indicate that soil quality is improved in arid system rain gardens. Such urban modifications both improve soils and reconnect ecohydrologic flows in Tucson neighborhoods, suggesting that the provision of ecosystem services in cities can be assisted with small scale green infrastructure modifications. In fact, such small scale improvements in ecosystem functioning may contribute to broader scale resilience of the urban ecosystem.

Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism.

PubMed

Vendeix, Franck A P; Murphy, Frank V; Cantara, William A; Leszczyńska, Grażyna; Gustilo, Estella M; Sproat, Brian; Malkiewicz, Andrzej; Agris, Paul F

2012-03-02

Human tRNA(Lys3)(UUU) (htRNA(Lys3)(UUU)) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm(5)s(2)U(34)), 2-methylthio-N(6)-threonylcarbamoyladenosine (ms(2)t(6)A(37)), and pseudouridine (Ψ(39)) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39)). Ribosome binding assays in vitro revealed that the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound AAA and AAG codons, whereas binding of the unmodified ASL(Lys3)(UUU) was barely detectable. The UV hyperchromicity, the circular dichroism, and the structural analyses indicated that Ψ(39) enhanced the thermodynamic stability of the ASL through base stacking while ms(2)t(6)A(37) restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular-dynamics-derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) bound to the 30S ribosomal subunit with each codon in the A site showed that the modified nucleotides mcm(5)s(2)U(34) and ms(2)t(6)A(37) participate in the stability of the anticodon-codon interaction. Importantly, the mcm(5)s(2)U(34)·G(3) wobble base pair is in the Watson-Crick geometry, requiring unusual hydrogen bonding to G in which mcm(5)s(2)U(34) must shift from the keto to the enol form. The results unambiguously demonstrate that modifications pre-structure the anticodon as a key prerequisite for efficient and accurate recognition of cognate and wobble codons. Copyright © 2011 Elsevier Ltd. All rights reserved.

SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D To Facilitate Viral Replication

PubMed Central

Liu, Yan; Shu, Bo; Meng, Jin; Zhang, Yuan; Zheng, Caishang; Ke, Xianliang; Gong, Peng; Hu, Qinxue; Wang, Hanzhong

2016-01-01

ABSTRACT Accumulating evidence suggests that viruses hijack cellular proteins to circumvent the host immune system. Ubiquitination and SUMOylation are extensively studied posttranslational modifications (PTMs) that play critical roles in diverse biological processes. Cross talk between ubiquitination and SUMOylation of both host and viral proteins has been reported to result in distinct functional consequences. Enterovirus 71 (EV71), an RNA virus belonging to the family Picornaviridae, is a common cause of hand, foot, and mouth disease. Little is known concerning how host PTM systems interact with enteroviruses. Here, we demonstrate that the 3D protein, an RNA-dependent RNA polymerase (RdRp) of EV71, is modified by small ubiquitin-like modifier 1 (SUMO-1) both during infection and in vitro. Residues K159 and L150/D151/L152 were responsible for 3D SUMOylation as determined by bioinformatics prediction combined with site-directed mutagenesis. Also, primer-dependent polymerase assays indicated that mutation of SUMOylation sites impaired 3D polymerase activity and virus replication. Moreover, 3D is ubiquitinated in a SUMO-dependent manner, and SUMOylation is crucial for 3D stability, which may be due to the interplay between the two PTMs. Importantly, increasing the level of SUMO-1 in EV71-infected cells augmented the SUMOylation and ubiquitination levels of 3D, leading to enhanced replication of EV71. These results together suggested that SUMO and ubiquitin cooperatively regulated EV71 infection, either by SUMO-ubiquitin hybrid chains or by ubiquitin conjugating to the exposed lysine residue through SUMOylation. Our study provides new insight into how a virus utilizes cellular pathways to facilitate its replication. IMPORTANCE Infection with enterovirus 71 (EV71) often causes neurological diseases in children, and EV71 is responsible for the majority of fatalities. Based on a better understanding of interplay between virus and host cell, antiviral drugs against enteroviruses may be developed. As a dynamic cellular process of posttranslational modification, SUMOylation regulates global cellular protein localization, interaction, stability, and enzymatic activity. However, little is known concerning how SUMOylation directly influences virus replication by targeting viral polymerase. Here, we found that EV71 polymerase 3D was SUMOylated during EV71 infection and in vitro. Moreover, the SUMOylation sites were determined, and in vitro polymerase assays indicated that mutations at SUMOylation sites could impair polymerase synthesis. Importantly, 3D is ubiquitinated in a SUMOylation-dependent manner that enhances the stability of the viral polymerase. Our findings indicate that the two modifications likely cooperatively enhance virus replication. Our study may offer a new therapeutic strategy against virus replication. PMID:27630238

Hydrocarbon-Based Polymer Electrolyte Membranes: Importance of Morphology on Ion Transport and Membrane Stability.

PubMed

Shin, Dong Won; Guiver, Michael D; Lee, Young Moo

2017-03-22

A fundamental understanding of polymer microstructure is important in order to design novel polymer electrolyte membranes (PEMs) with excellent electrochemical performance and stabilities. Hydrocarbon-based polymers have distinct microstructure according to their chemical structure. The ionic clusters and/or channels play a critical role in PEMs, affecting ion conductivity and water transport, especially at medium temperature and low relative humidity (RH). In addition, physical properties such as water uptake and dimensional swelling behavior depend strongly on polymer morphology. Over the past few decades, much research has focused on the synthetic development and microstructural characterization of hydrocarbon-based PEM materials. Furthermore, blends, composites, pressing, shear field, electrical field, surface modification, and cross-linking have also been shown to be effective approaches to obtain/maintain well-defined PEM microstructure. This review summarizes recent work on developments in advanced PEMs with various chemical structures and architecture and the resulting polymer microstructures and morphologies that arise for potential application in fuel cell, lithium ion battery, redox flow battery, actuators, and electrodialysis.

A short essay on quantum black holes and underlying noncommutative quantized space-time

NASA Astrophysics Data System (ADS)

Tanaka, Sho

2017-01-01

We emphasize the importance of noncommutative geometry or Lorenz-covariant quantized space-time towards the ultimate theory of quantum gravity and Planck scale physics. We focus our attention on the statistical and substantial understanding of the Bekenstein-Hawking area-entropy law of black holes in terms of the kinematical holographic relation (KHR). KHR manifestly holds in Yang’s quantized space-time as the result of kinematical reduction of spatial degrees of freedom caused by its own nature of noncommutative geometry, and plays an important role in our approach without any recourse to the familiar hypothesis, so-called holographic principle. In the present paper, we find a unified form of KHR applicable to the whole region ranging from macroscopic to microscopic scales in spatial dimension d  =  3. We notice a possibility of nontrivial modification of area-entropy law of black holes which becomes most remarkable in the extremely microscopic system close to Planck scale.

Human photosensitivity: from pathophysiology to treatment.

PubMed

Verrotti, A; Tocco, A M; Salladini, C; Latini, G; Chiarelli, F

2005-11-01

Photosensitivity is a condition detected on the electroencephalography (EEG) as a paroxysmal reaction to Intermittent Photic Stimulation (IPS). This EEG response, elicited by IPS or by other visual stimuli of daily life, is called Photo Paroxysmal Response (PPR). PPRs are well documented in epileptic and non-epileptic subjects. Photosensitivity rarely in normal individuals evolves into epilepsy. Photosensitive epilepsy is a rare refex epilepsy characterized by seizures in photosensitive individuals. The development of modern technology has increased the exposition to potential seizure precipitants in people of all ages, but especially in children and adolescents. Actually, videogames, computers and televisions are the most common triggers in daily life of susceptible persons. The mechanisms of generation of PPR are poorly understood, but genetic factors play an important rule. The control of visually induced seizures has, generally a good prognosis. In patients known to be visually sensitive, avoidance of obvious source and stimulus modifications are very important and useful to seizure prevention, but in the large majority of patients with epilepsy and photosensitivity antiepileptic drugs are needed.

Neutralized ion beam modification of cellulose membranes for study of ion charge effect on ion-beam-induced DNA transfer

NASA Astrophysics Data System (ADS)

Prakrajang, K.; Sangwijit, K.; Anuntalabhochai, S.; Wanichapichart, P.; Yu, L. D.

2012-02-01

Low-energy ion beam biotechnology (IBBT) has recently been rapidly developed worldwide. Ion-beam-induced DNA transfer is one of the important applications of IBBT. However, mechanisms involved in this application are not yet well understood. In this study plasma-neutralized ion beam was applied to investigate ion charge effect on induction of DNA transfer. Argon ion beam at 7.5 keV was neutralized by RF-driven plasma in the beam path and then bombarded cellulose membranes which were used as the mimetic plant cell envelope. Electrical properties such as impedance and capacitance of the membranes were measured after the bombardment. An in vitro experiment on plasmid DNA transfer through the cellulose membrane was followed up. The results showed that the ion charge input played an important role in the impedance and capacitance changes which would affect DNA transfer. Generally speaking, neutral particle beam bombardment of biologic cells was more effective in inducing DNA transfer than charged ion beam bombardment.

Glancing angle RF sheaths

NASA Astrophysics Data System (ADS)

D'Ippolito, D. A.; Myra, J. R.

2013-10-01

RF sheaths occur in tokamaks when ICRF waves encounter conducting boundaries. The sheath plays an important role in determining the efficiency of ICRF heating, the impurity influxes from the edge plasma, and the plasma-facing component damage. An important parameter in sheath theory is the angle θ between the equilibrium B field and the wall. Recent work with 1D and 2D sheath models has shown that the rapid variation of θ around a typical limiter can lead to enhanced sheath potentials and localized power deposition (hot spots) when the B field is near glancing incidence. The physics model used to obtain these results does not include some glancing-angle effects, e.g. possible modification of the angular dependence of the Child-Langmuir law and the role of the magnetic pre-sheath. Here, we report on calculations which explore these effects, with the goal of improving the fidelity of the rf sheath BC used in analytical and numerical calculations. Work supported by US DOE grants DE-FC02-05ER54823 and DE-FG02-97ER54392.

Can probiotics benefit children with autism spectrum disorders?

PubMed Central

Navarro, Fernando; Liu, Yuying; Rhoads, Jon Marc

2016-01-01

Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome. The present review presents a number of reported clinical, immunological and microbiome-related changes seen in children with autism compared to normally developed children. It also discusses gut inflammation, permeability concerns, and absorption abnormalities that may contribute to these problems. Most importantly, it discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism. PMID:28028357

Epidemiology of gastric cancer in Japan

PubMed Central

Inoue, M; Tsugane, S

2005-01-01

Despite its decreasing trend in Japan, gastric cancer remains an important public health problem. Although the age standardised rates of gastric cancer have been declining for decades, the absolute numbers are increasing because of the rapid aging of the population. A large proportion of Japanese gastric cancers are detected at an early stage, with a better overall survival rate. As with Western developed countries, a change in the social environment such as reduced salt use and increased fresh vegetable and fruit intake as well as improvement of food storage may play an important part in the decline. Differences in Helicobacter pylori infection rates between generations presumably have contributed to the generation related variation in the declining trends. It is expected that most gastric cancers in Japan may be preventable by lifestyle modification such as salt reduction and increased fruit and vegetable intake, together with avoidance of smoking and countermeasures against H pylori infection so that the level now evident in Western developed countries can be reached. PMID:15998815

Potassium (K+) gradients serve as a mobile energy source in plant vascular tissues.

PubMed

Gajdanowicz, Pawel; Michard, Erwan; Sandmann, Michael; Rocha, Marcio; Corrêa, Luiz Gustavo Guedes; Ramírez-Aguilar, Santiago J; Gomez-Porras, Judith L; González, Wendy; Thibaud, Jean-Baptiste; van Dongen, Joost T; Dreyer, Ingo

2011-01-11

The essential mineral nutrient potassium (K(+)) is the most important inorganic cation for plants and is recognized as a limiting factor for crop yield and quality. Nonetheless, it is only partially understood how K(+) contributes to plant productivity. K(+) is used as a major active solute to maintain turgor and to drive irreversible and reversible changes in cell volume. K(+) also plays an important role in numerous metabolic processes, for example, by serving as an essential cofactor of enzymes. Here, we provide evidence for an additional, previously unrecognized role of K(+) in plant growth. By combining diverse experimental approaches with computational cell simulation, we show that K(+) circulating in the phloem serves as a decentralized energy storage that can be used to overcome local energy limitations. Posttranslational modification of the phloem-expressed Arabidopsis K(+) channel AKT2 taps this "potassium battery," which then efficiently assists the plasma membrane H(+)-ATPase in energizing the transmembrane phloem (re)loading processes.

The effects of divergent and nondivergent winds on the kinetic energy budget of a mid-latitude cyclone - A case study

NASA Technical Reports Server (NTRS)

Chen, T.-C.; Alpert, J. C.; Schlatter, T. W.

1978-01-01

The magnitude of the divergent component of the wind is relatively small compared to that of the nondivergent component in large-scale atmospheric flows; nevertheless, it plays an important role in the case of explosive cyclogenesis examined here. The kinetic energy budget for the life cycle of an intense, developing cyclone over North America is calculated. The principal kinetic energy source is the net horizontal transport across the boundaries of the region enclosing the cyclone. By investigating the relative importance of the divergent and nondivergent wind components in the kinetic energy budget, it was found, as expected, that neglecting the divergent wind component in calculating the magnitude of the kinetic energy is of little consequence, but that the horizontal flux convergence and generation of kinetic energy depend crucially upon the divergent component. Modification of the divergent wind component can result in significant changes in the kinetic energy budget of the synoptic system.

Mechanosensitive neurons on the internal reproductive tract contribute to egg-laying-induced acetic acid attraction in Drosophila

PubMed Central

Gou, Bin; Liu, Ying; Guntur, Ananya R.; Stern, Ulrich; Yang, Chung-Hui

2014-01-01

Selecting a suitable site to deposit their eggs is an important reproductive need of Drosophila females. While their choosiness towards egg-laying sites is well documented, the specific neural mechanism that activates females’ search for attractive egg-laying sites is not known. Here we show that distention/contraction of females’ internal reproductive tract triggered by egg-delivery through the tract plays a critical role in activating such search. We found that females start to exhibit acetic acid attraction prior to depositing each egg but no attraction when they are not laying eggs. Artificially distending the reproductive tract triggers acetic acid attraction in non-egg-laying females whereas silencing the mechanosensitive neurons we identified that can sense the contractile status of the tract eliminates such attraction. Our work uncovers the circuit basis of an important reproductive need of Drosophila females and provides a simple model to dissect the neural mechanism that underlies a reproductive need-induced behavioral modification. PMID:25373900

Potassium (K+) gradients serve as a mobile energy source in plant vascular tissues

PubMed Central

Gajdanowicz, Pawel; Michard, Erwan; Sandmann, Michael; Rocha, Marcio; Corrêa, Luiz Gustavo Guedes; Ramírez-Aguilar, Santiago J.; Gomez-Porras, Judith L.; González, Wendy; Thibaud, Jean-Baptiste; van Dongen, Joost T.; Dreyer, Ingo

2011-01-01

The essential mineral nutrient potassium (K+) is the most important inorganic cation for plants and is recognized as a limiting factor for crop yield and quality. Nonetheless, it is only partially understood how K+ contributes to plant productivity. K+ is used as a major active solute to maintain turgor and to drive irreversible and reversible changes in cell volume. K+ also plays an important role in numerous metabolic processes, for example, by serving as an essential cofactor of enzymes. Here, we provide evidence for an additional, previously unrecognized role of K+ in plant growth. By combining diverse experimental approaches with computational cell simulation, we show that K+ circulating in the phloem serves as a decentralized energy storage that can be used to overcome local energy limitations. Posttranslational modification of the phloem-expressed Arabidopsis K+ channel AKT2 taps this “potassium battery,” which then efficiently assists the plasma membrane H+-ATPase in energizing the transmembrane phloem (re)loading processes. PMID:21187374

Advances in esophageal cancer: A new perspective on pathogenesis associated with long non-coding RNAs.

PubMed

Huang, Xiaomei; Zhou, Xi; Hu, Qing; Sun, Binyu; Deng, Mingming; Qi, Xiaolong; Lü, Muhan

2018-01-28

Esophageal cancer is a malignant digestive tract cancer with high mortality. Although studies have found that esophageal cancer is involved in a complex and important gene regulation network, the pathogenesis remains unclear. The recently described long non-coding RNAs (lncRNAs) are one effective part of the gene regulation network. However, in past decades, lncRNAs were thought to be "transcript noise" or "pseudogenes" and were thus ignored. Early studies indicated that lncRNAs play pivotal roles during evolution. However, in recent years, increasing research has revealed that many lncRNAs are associated with tumorigenesis. In particular, lncRNAs may act as important elements for epigenetic regulation, transcription, post-transcriptional regulation and post-translational modification of proteins. Additionally, they may be novel biomarkers for tumors and therapeutic targets in cancer. Here, we summarize the functions of lncRNAs in esophageal cancer, with an emphasis on lncRNA-mediated regulatory mechanisms that affect the biological characteristics of esophageal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characterization, tissue distribution and expression analysis of TRIM25 in Gallus gallus domesticus.

PubMed

Feng, Ze-Qing; Cheng, Yang; Yang, Hui-Ling; Zhu, Qing; Yu, Dandan; Liu, Yi-Ping

2015-04-25

TRIM25, a member of the tripartite motif-containing (TRIM) family of proteins, plays an important role in cell proliferation, protein modification, and the RIG-I-mediated antiviral signaling pathway. However, relatively few studies have investigated the molecular characterization, tissue distribution, and potential function of TRIM25 in chickens. In this study, we cloned the full-length cDNA of chicken TRIM25 that is composed of 2706 bp. Sequence analyses revealed that TRIM25 contains a 1902-bp open-reading frame that probably encodes a 633-amino acid protein. Multiple comparisons with deduced amino acid sequences revealed that the RING finger and B30.2 domains of chicken TRIM25 share a high sequence similarity with human and murine TRIM25, indicating that these domains are critical for the function of chicken TRIM25. qPCR assays revealed that TRIM25 is highly expressed in the spleen, thymus and lungs in chickens. Furthermore, we observed that TRIM25 expression was significantly upregulated both in vitro and in vivo following infection with Newcastle disease virus. TRIM25 expression was also significantly upregulated in chicken embryo fibroblasts upon stimulation with poly(I:C) or poly(dA:dT). Taken together, these findings suggest that TRIM25 plays an important role in antiviral signaling pathways in chickens. Copyright © 2015 Elsevier B.V. All rights reserved.

Aqueous sodium borohydride induced thermally stable porous zirconium oxide for quick removal of lead ions

PubMed Central

Nayak, Nadiya B.; Nayak, Bibhuti B.

2016-01-01

Aqueous sodium borohydride (NaBH4) is well known for its reducing property and well-established for the development of metal nanoparticles through reduction method. In contrary, this research paper discloses the importance of aqueous NaBH4 as a precipitating agent towards development of porous zirconium oxide. The boron species present in aqueous NaBH4 play an active role during gelation as well as phase separated out in the form of boron complex during precipitation, which helps to form boron free zirconium hydroxide [Zr(OH)4] in the as-synthesized condition. Evolved in-situ hydrogen (H2) gas-bubbles also play an important role to develop as-synthesized loose zirconium hydroxide and the presence of intra-particle voids in the loose zirconium hydroxide help to develop porous zirconium oxide during calcination process. Without any surface modification, this porous zirconium oxide quickly adsorbs almost hundred percentages of toxic lead ions from water solution within 15 minutes at normal pH condition. Adsorption kinetic models suggest that the adsorption process was surface reaction controlled chemisorption. Quick adsorption was governed by surface diffusion process and the adsorption kinetic was limited by pore diffusion. Five cycles of adsorption-desorption result suggests that the porous zirconium oxide can be reused efficiently for removal of Pb (II) ions from aqueous solution. PMID:26980545

TRIM45 negatively regulates NF-{kappa}B-mediated transcription and suppresses cell proliferation

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

Shibata, Mio; Sato, Tomonobu; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638

2012-06-22

Highlights: Black-Right-Pointing-Pointer NF-{kappa}B plays an important role in cell survival and carcinogenesis. Black-Right-Pointing-Pointer TRIM45 negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription. Black-Right-Pointing-Pointer TRIM45 overexpression suppresses cell growth. Black-Right-Pointing-Pointer TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth. -- Abstract: The NF-{kappa}B signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-{kappa}B is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-{kappa}B signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin-proteasome system. It has been reported that overexpression of TRIM45, one ofmore » the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNF{alpha}-induced NF-{kappa}B-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-{kappa}B signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-{kappa}B signal and regulates cell growth.« less

The Role of Water in the Stability of Wild Type and Mutant Insulin Dimers.

PubMed

Raghunathan, Shampa; El Hage, Krystel; Desmond, Jasmine; Zhang, Lixian; Meuwly, Markus

2018-06-19

Insulin dimerization and aggregation play important roles in the endogenous delivery of the hormone. One of the important residues at the insulin dimer interface is Phe B24 which is an invariant aromatic anchor that packs towards its own monomer inside a hydrophobic cavity formed by Val B12 , Leu B15 , Tyr B16 , Cys B19 and Tyr B26 . Using molecular dynamics and free energy simulations in explicit solvent, the structural and dynamical consequences of mutations of Phe at position B24 to Gly, Ala, and d-Ala and the des-PheB25 variant are quantified. Consistent with experiments it is found that the Gly and Ala modifications lead to insulin dimers with reduced stability by 4 and 5 kcal/mol from thermodynamic integration and 4 and 8 kcal/mol from results using MM-GBSA, respectively. Given the experimental difficulties to quantify the thermodynamic stability of modified insulin dimers, such computations provide a valuable complement. Interestingly, the Gly-mutant exists as a strongly and a weakly interacting dimer. Analysis of the molecular dynamics simulations shows that this can be explained by water molecules that replace direct monomer-monomer H-bonding contacts at the dimerization interface involving residues B24 to B26. It is concluded that such solvent molecules play an essential role and must be included in future insulin dimerization studies.

Sinking Jelly-Carbon Unveils Potential Environmental Variability along a Continental Margin

PubMed Central

Lebrato, Mario; Molinero, Juan-Carlos; Cartes, Joan E.; Lloris, Domingo; Mélin, Frédéric; Beni-Casadella, Laia

2013-01-01

Particulate matter export fuels benthic ecosystems in continental margins and the deep sea, removing carbon from the upper ocean. Gelatinous zooplankton biomass provides a fast carbon vector that has been poorly studied. Observational data of a large-scale benthic trawling survey from 1994 to 2005 provided a unique opportunity to quantify jelly-carbon along an entire continental margin in the Mediterranean Sea and to assess potential links with biological and physical variables. Biomass depositions were sampled in shelves, slopes and canyons with peaks above 1000 carcasses per trawl, translating to standing stock values between 0.3 and 1.4 mg C m2 after trawling and integrating between 30,000 and 175,000 m2 of seabed. The benthopelagic jelly-carbon spatial distribution from the shelf to the canyons may be explained by atmospheric forcing related with NAO events and dense shelf water cascading, which are both known from the open Mediterranean. Over the decadal scale, we show that the jelly-carbon depositions temporal variability paralleled hydroclimate modifications, and that the enhanced jelly-carbon deposits are connected to a temperature-driven system where chlorophyll plays a minor role. Our results highlight the importance of gelatinous groups as indicators of large-scale ecosystem change, where jelly-carbon depositions play an important role in carbon and energy transport to benthic systems. PMID:24367499

Modification of Baselines for Gasoline Produced or Imported for Use in Hawaii, Alaska, and U.S. Territories Additional Resources

EPA Pesticide Factsheets

This documents for modifications to fuel regulations to allow refiners and importers of conventional gasoline used in Hawaii, Alaska and U.S. Territories to petition EPA to change the way in which they calculate emissions from such gasoline.

Epigenetics of inflammation, maternal infection and nutrition

USDA-ARS?s Scientific Manuscript database

Studies have demonstrated that epigenetic changes such as DNA methylation, histone modification, and chromatin remodeling are linked to an increased inflammatory response as well as increased risk for chronic disease development. A few studies have begun to investigate whether dietary nutrients play...

Therapeutic implications of diabetes in cardiovascular disease.

PubMed

Cherian, Biju; Meka, Naga; Katragadda, Srikanth; Arora, Rohit

2009-01-01

Insulin-resistant diabetes is becoming more prevalent among the general U.S. population. Approximately 20 million people had diabetes in 2005, of which one third of the population had impaired fasting glucose. The prevalence rate is 9%, a more alarming rate in the 20- to 39-year age group, which suggests a significant degree of how even the young are affected. We review how the prediabetic stage (impaired glucose tolerance-impaired fasting glucose and impaired glucose tolerance-impaired glucose tolerance) plays a vital role as a risk factor for cardiovascular disease, and the effectiveness of lifestyle modifications with drug therapy reduces the cardiovascular risk of early diabetes and its complications. A lifestyle modification like effective weight loss and exercise, with or without antidiabetic drugs, prevents the proatherogenic effects of diabetes. Controlled, randomized studies have shown that progression to diabetes among those with prediabetes is not inevitable; people with prediabetes who lose weight and increase their physical activity can prevent or delay diabetes and could even return their blood glucose levels to normal. Although prevention of prediabetes is a huge challenge, a tight glycemic control with lifestyle modifications and antihyperglycemics like thiazolidinediones play a vital role in increasing the insulin sensitivity of tissues and decreasing the cardiovascular risk factor of diabetes.

Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: a revision.

PubMed

Pogoda, Kristin; Kameritsch, Petra; Retamal, Mauricio A; Vega, José L

2016-05-24

Post-translational modifications of connexins play an important role in the regulation of gap junction and hemichannel permeability. The prerequisite for the formation of functional gap junction channels is the assembly of connexin proteins into hemichannels and their insertion into the membrane. Hemichannels can affect cellular processes by enabling the passage of signaling molecules between the intracellular and extracellular space. For the intercellular communication hemichannels from one cell have to dock to its counterparts on the opposing membrane of an adjacent cell to allow the transmission of signals via gap junctions from one cell to the other. The controlled opening of hemichannels and gating properties of complete gap junctions can be regulated via post-translational modifications of connexins. Not only channel gating, but also connexin trafficking and assembly into hemichannels can be affected by post-translational changes. Recent investigations have shown that connexins can be modified by phosphorylation/dephosphorylation, redox-related changes including effects of nitric oxide (NO), hydrogen sulfide (H2S) or carbon monoxide (CO), acetylation, methylation or ubiquitination. Most of the connexin isoforms are known to be phosphorylated, e.g. Cx43, one of the most studied connexin at all, has 21 reported phosphorylation sites. In this review, we provide an overview about the current knowledge and relevant research of responsible kinases, connexin phosphorylation sites and reported effects on gap junction and hemichannel regulation. Regarding the effects of oxidants we discuss the role of NO in different cell types and tissues and recent studies about modifications of connexins by CO and H2S.

Health behaviour advice from health professionals to Canadian adults with hypertension: results from a national survey.

PubMed

Walker, Robin L; Gee, Marianne E; Bancej, Christina; Nolan, Robert P; Kaczorowski, Janusz; Joffres, Michel; Bienek, Asako; Gwadry-Sridhar, Femida; Campbell, Norman R C

2011-01-01

Health professionals play an important role in providing health information to patients. The objectives of this study were to examine the type of advice that Canadians with hypertension recall receiving from health professionals to manage their condition, and to assess if there is an association between health behaviour advice provided by health professionals and self-reported engagement in health behaviour modification. Respondents of the 2009 Survey on Living with Chronic Diseases in Canada (N = 6142) were asked about sociodemographic characteristics, health care utilization, and health behaviour modification to control hypertension. Association between receipt of advice from health professional and ever engaging, continuing to engage, and not engaging in health behaviour modification was quantified by prevalence rate ratios. Most participants (90.9%; 95% confidence interval [CI], 89.6-92.2) reported that the health professional most responsible for treating their high blood pressure was their general practitioner. Approximately 9% reported that they had not received or do not recall receiving any advice for blood pressure control. The most commonly reported advice received from a health professional was to participate in physical activity or exercise (70.0%). Respondents who had received advice on health behaviour change to manage their high blood pressure were more likely to report engaging in the behaviour compared with those who did not receive such advice. Many Canadians with hypertension receive health behaviour change advice from their health professionals. Receiving this advice was associated with a greater likelihood of attempting health behaviour change and attempting to sustain that change. Copyright © 2011 Canadian Cardiovascular Society. All rights reserved.

Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex

NASA Technical Reports Server (NTRS)

Chen, W. R.; Lee, S.; Kato, K.; Spencer, D. D.; Shepherd, G. M.; Williamson, A.

1996-01-01

The primate temporal cortex has been demonstrated to play an important role in visual memory and pattern recognition. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here we address this issue by examining the induction of synaptic plasticity in surgically resected human inferior and middle temporal cortex. The results show that synaptic strength in the human temporal cortex could undergo bidirectional modifications, depending on the pattern of conditioning stimulation. High frequency stimulation (100 or 40 Hz) in layer IV induced long-term potentiation (LTP) of both intracellular excitatory postsynaptic potentials and evoked field potentials in layers II/III. The LTP induced by 100 Hz tetanus was blocked by 50-100 microM DL-2-amino-5-phosphonovaleric acid, suggesting that N-methyl-D-aspartate receptors were responsible for its induction. Long-term depression (LTD) was elicited by prolonged low frequency stimulation (1 Hz, 15 min). It was reduced, but not completely blocked, by DL-2-amino-5-phosphonovaleric acid, implying that some other mechanisms in addition to N-methyl-DL-aspartate receptors were involved in LTD induction. LTD was input-specific, i.e., low frequency stimulation of one pathway produced LTD of synaptic transmission in that pathway only. Finally, the LTP and LTD could reverse each other, suggesting that they can act cooperatively to modify the functional state of cortical network. These results suggest that LTP and LTD are possible mechanisms for the visual memory and pattern recognition functions performed in the human temporal cortex.

Identification of DNA Methyltransferase Genes in Human Pathogenic Bacteria by Comparative Genomics.

PubMed

Brambila-Tapia, Aniel Jessica Leticia; Poot-Hernández, Augusto Cesar; Perez-Rueda, Ernesto; Rodríguez-Vázquez, Katya

2016-06-01

DNA methylation plays an important role in gene expression and virulence in some pathogenic bacteria. In this report, we describe DNA methyltransferases (MTases) present in human pathogenic bacteria and compared them with related species, which are not pathogenic or less pathogenic, based in comparative genomics. We performed a search in the KEGG database of the KEGG database orthology groups associated with adenine and cytosine DNA MTase activities (EC: 2.1.1.37, EC: 2.1.1.113 and EC: 2.1.1.72) in 37 human pathogenic species and 18 non/less pathogenic relatives and performed comparisons of the number of these MTases sequences according to their genome size, the DNA MTase type and with their non-less pathogenic relatives. We observed that Helicobacter pylori and Neisseria spp. presented the highest number of MTases while ten different species did not present a predicted DNA MTase. We also detected a significant increase of adenine MTases over cytosine MTases (2.19 vs. 1.06, respectively, p < 0.001). Adenine MTases were the only MTases associated with restriction modification systems and DNA MTases associated with type I restriction modification systems were more numerous than those associated with type III restriction modification systems (0.84 vs. 0.17, p < 0.001); additionally, there was no correlation with the genome size and the total number of DNA MTases, indicating that the number of DNA MTases is related to the particular evolution and lifestyle of specific species, regulating the expression of virulence genes in some pathogenic bacteria.

The effects of linguistic modification on ESL students' comprehension of nursing course test items.

PubMed

Bosher, Susan; Bowles, Melissa

2008-01-01

Recent research has indicated that language may be a source of construct-irrelevant variance for non-native speakers of English, or English as a second language (ESL) students, when they take exams. As a result, exams may not accurately measure knowledge of nursing content. One accommodation often used to level the playing field for ESL students is linguistic modification, a process by which the reading load of test items is reduced while the content and integrity of the item are maintained. Research on the effects of linguistic modification has been conducted on examinees in the K-12 population, but is just beginning in other areas. This study describes the collaborative process by which items from a pathophysiology exam were linguistically modified and subsequently evaluated for comprehensibility by ESL students. Findings indicate that in a majority of cases, modification improved examinees' comprehension of test items. Implications for test item writing and future research are discussed.

Electric-field-induced modification in Curie temperature of Co monolayer on Pt(111)

NASA Astrophysics Data System (ADS)

Nakamura, Kohji; Oba, Mikito; Akiyama, Toru; Ito, Tomonori; Weinert, Michael

2015-03-01

Magnetism induced by an external electric field (E-field) has received much attention as a potential approach for controlling magnetism at the nano-scale with the promise of ultra-low energy power consumption. Here, the E-field-induced modification of the Curie temperature for a prototypical transition-metal thin layer of a Co monolayer on Pt(111) is investigated by first-principles calculations by using the full-potential linearized augmented plane wave method that treats spin-spiral structures in an E-field. An applied E-field modifies the magnon (spin-spiral formation) energies by a few meV, which leads to a modification of the exchange pair interaction parameters within the classical Heisenberg model. With inclusion of the spin-orbit coupling (SOC), the magnetocrystalline anisotropy and the Dzyaloshinskii-Morita interaction are obtained by the second variation SOC method. An E-field-induced modification of the Curie temperature is demonstrated by Monte Carlo simulations, in which a change in the exchange interaction is found to play a key role.

First report of nonpsychotic self-cannibalism (autophagy), tongue splitting, and scar patterns (scarification) as an extreme form of cultural body modification in a western civilization.

PubMed

Benecke, M

1999-09-01

As part of her current lifestyle, a 28-year-old Caucasian woman routinely injures and allows subsequent healing of her skin and other tissues. Her body modifications include a "split tongue" (a tongue split to the base), which does not interfere with speaking and eating. Other modifications include large scarification patterns produced by branding and cutting. This woman has been known to eat parts of her skin that were previously cut out of her body. She also performs "needle play" by allowing medical syringe needles to be lodged temporarily under her skin. The patient had a normal childhood, is currently employed full-time as an office manager, and is psychologically stable. Although one other case of self-induced penoscrotal hypospadias is known, this is the only report of extensive, nonpsychotic, autodestructive behavior. However, this may not be the case in the future as an increasing number of young individuals have become interested in body modifications.

Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases.

PubMed

Chen, Beidi; Sun, Luxi; Zhang, Xuan

2017-09-01

The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance. Epigenetic modifications triggered by environmental factors is an important mechanism that leads to altered gene expression. Researches addressing the role of DNA methylation, histone modification and non-coding RNA in AIDs have been increasing in recent years. Furthermore, studies showed that human microbiota and their metabolites can regulate immune cells and cytokines via epigenomic modifications. For example, short-chain fatty acids (SCFAs) produced by gut microbiota promote the differentiation of naïve T cell into Treg by suppressing histone deacetylases (HDACs). Therefore, we propose that dysbiosis and resulting metabolites may cause aberrant immune responses via epigenetic modifications, and lead to AIDs. With the development of high-throughput sequencing, metagenome analysis has been applied to investigate the dysbiosis in AIDs patients. We have tested the fecal, dental and salivary samples from treatment-naïve rheumatoid arthritis (RA) individuals by metagenomic shotgun sequencing and a metagenome-wide association study. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially restored after treatment. We also found functional changes of microbiota and molecular mimicry of human antigens in RA individuals. By integrating the analysis of multi-omics of microbiome and epigenome, we could explore the interaction between human immune system and microbiota, and thereby unmasking specific and more sensitive biomarkers as well as potential therapeutic targets. Future studies aiming at the crosstalk between human dysbiosis and epigenetic modifications and their influences on AIDs will facilitate our understanding and better managing of these debilitating AIDs. Copyright © 2017 Elsevier Ltd. All rights reserved.

78 FR 3367 - Modification of Regulation Regarding the Extension of Time Limits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

...-2747-01] RIN 0625-AA94 Modification of Regulation Regarding the Extension of Time Limits AGENCY: Import... the extension of time limits for submissions in antidumping (AD) and countervailing duty (CVD) proceedings. The modification, if adopted, will clarify that parties may request an extension of time limits...

Early Lung Cancer Detection via Global Protein Modification Profiles

DTIC Science & Technology

2013-12-01

Increased DNMT1 protein expression has also been shown to play a critical role in the malignant progression of hepatocellular carcinoma (HCC) and be a...the Malignant Potential and Poor Prognosis of Human Hepatocellular Carcinomas , Int. J. Cancer, 105:527-532.

75 FR 77919 - Carolina Power & Light Company Shearon Harris Nuclear Power Plant, Unit 1; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... involves important physical modifications to the HNP, Unit 1 security system. There are several issues... in which some important security modifications are planned. A direct outside access route to the... implementation deadline, the licensee currently maintains a security system acceptable to the NRC and that will...

Connexin and Pannexin hemichannels are regulated by redox potential

PubMed Central

Retamal, Mauricio A.

2014-01-01

Connexins (Cxs) and Pannexins (Panxs) are two non-related protein families, having both the property to form hemichannels at the plasma membrane. There are 21 genes coding for different Cx based proteins and only 3 for Panx. Under physiological conditions, these hemichannels (Cxs and Panxs) present a low open probability, but when open, they allow the release of signaling molecules to the extracellular space. However, under pathological conditions, these hemichannels increase their open probability, inducing important lysis of metabolites, and ionic imbalance, which in turn induce the massive entry of Ca+2 to the cell. Actually, it is well recognized that Cxs and Panxs based channels play an important role in several diseases and -in many cases- this is associated with an aberrant hemichannel opening. Hemichannel opening and closing are controlled by a plethora of signaling including changes of the voltage plasma membrane, protein-protein interactions, and several posttranslational modifications, including protein cleavage, phosphorylation, glycosylation, hydroxylation and S-nitrosylation, among others. In particular, it has been recently shown that the cellular redox status modulates the opening/closing and permeability of at least Cx43, Cx46, and Panx1 hemichannels. Thus, for example, the gaseous transmitter nitric oxide (NO) can induce the S-nitrosylation of these proteins modulating in turn several of their properties. The reason is that the redox status of a cell is fundamental to set their response to the environment and also plays an important role in several pathologies. In this review, I will discuss how NO and other molecules associated with redox signaling modulate Cxs and Panx hemichannels properties. PMID:24611056

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

Vendeix, Franck A.P.; Murphy, IV, Frank V.; Cantara, William A.

Human tRNA Lys3 UUU (htRNA Lys3 UUU) decodes the lysine codons AAA and AAG during translation and also plays a crucial role as the primer for HIV-1 (human immunodeficiency virus type 1) reverse transcription. The posttranscriptional modifications 5-methoxycarbonylmethyl-2-thiouridine (mcm 5s 2U 34), 2-methylthio-N 6-threonylcarbamoyladenosine (ms 2t 6A 37), and pseudouridine (Ψ 39) in the tRNA's anticodon domain are critical for ribosomal binding and HIV-1 reverse transcription. To understand the importance of modified nucleoside contributions, we determined the structure and function of this tRNA's anticodon stem and loop (ASL) domain with these modifications at positions 34, 37, and 39, respectively (hASLmore » Lys3 UUU-mcm 5s 2U 34;ms 2t 6A 37;Ψ 39). Ribosome binding assays in vitro revealed that the hASL Lys3 UUU-mcm 5s 2U 34;ms 2t 6A 37;Ψ 39 bound AAA and AAG codons, whereas binding of the unmodified ASL Lys3 UUU was barely detectable. The UV hyperchromicity, the circular dichroism, and the structural analyses indicated that Ψ 39 enhanced the thermodynamic stability of the ASL through base stacking while ms 2t 6A 37 restrained the anticodon to adopt an open loop conformation that is required for ribosomal binding. The NMR-restrained molecular-dynamics-derived solution structure revealed that the modifications provided an open, ordered loop for codon binding. The crystal structures of the hASL Lys3 UUU-mcm 5s 2U 34;ms 2t 6A 37;Ψ 39 bound to the 30S ribosomal subunit with each codon in the A site showed that the modified nucleotides mcm 5s 2U 34 and ms 2t 6A 37 participate in the stability of the anticodon–codon interaction. Importantly, the mcm 5s 2U 34·G 3 wobble base pair is in the Watson–Crick geometry, requiring unusual hydrogen bonding to G in which mcm 5s 2U 34 must shift from the keto to the enol form. The results unambiguously demonstrate that modifications pre-structure the anticodon as a key prerequisite for efficient and accurate recognition of cognate and wobble codons.« less

Global urban signatures of phenotypic change in animal and plant populations

PubMed Central

Correa, Cristian; Marzluff, John M.; Hendry, Andrew P.; Palkovacs, Eric P.; Hunt, Victoria M.; Apgar, Travis M.; Zhou, Yuyu

2017-01-01

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms. This paper presents evidence on the mechanisms linking urban development patterns to rapid evolutionary changes for species that play important functional roles in communities and ecosystems. Through a metaanalysis of experimental and observational studies reporting more than 1,600 phenotypic changes in species across multiple regions, we ask whether we can discriminate an urban signature of phenotypic change beyond the established natural baselines and other anthropogenic signals. We then assess the relative impact of five types of urban disturbances including habitat modifications, biotic interactions, habitat heterogeneity, novel disturbances, and social interactions. Our study shows a clear urban signal; rates of phenotypic change are greater in urbanizing systems compared with natural and nonurban anthropogenic systems. By explicitly linking urban development to traits that affect ecosystem function, we can map potential ecoevolutionary implications of emerging patterns of urban agglomerations and uncover insights for maintaining key ecosystem functions upon which the sustainability of human well-being depends. PMID:28049817

Global urban signatures of phenotypic change in animal and plant populations.

PubMed

Alberti, Marina; Correa, Cristian; Marzluff, John M; Hendry, Andrew P; Palkovacs, Eric P; Gotanda, Kiyoko M; Hunt, Victoria M; Apgar, Travis M; Zhou, Yuyu

2017-08-22

Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms. This paper presents evidence on the mechanisms linking urban development patterns to rapid evolutionary changes for species that play important functional roles in communities and ecosystems. Through a metaanalysis of experimental and observational studies reporting more than 1,600 phenotypic changes in species across multiple regions, we ask whether we can discriminate an urban signature of phenotypic change beyond the established natural baselines and other anthropogenic signals. We then assess the relative impact of five types of urban disturbances including habitat modifications, biotic interactions, habitat heterogeneity, novel disturbances, and social interactions. Our study shows a clear urban signal; rates of phenotypic change are greater in urbanizing systems compared with natural and nonurban anthropogenic systems. By explicitly linking urban development to traits that affect ecosystem function, we can map potential ecoevolutionary implications of emerging patterns of urban agglomerations and uncover insights for maintaining key ecosystem functions upon which the sustainability of human well-being depends.

Melanoma differentiation associated gene-7/interleukin-24 induces caspase-3 denitrosylation to facilitate the activation of cancer cell apoptosis.

PubMed

Tian, Hui; Zhang, De-Fang; Zhang, Bao-Fu; Li, Hui-Zhong; Zhang, Qing; Li, Lian-Tao; Pei, Dong-Sheng; Zheng, Jun-Nian

2015-03-01

Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) induces caspase-3 cleavage and subsequent activation via the intrinsic or extrinsic pathway to result in cancer cell-selective apoptosis, but whether mda-7/IL-24 may directly regulate caspase-3 through the post-translational modification remains unknown. Here, we reported that tumor-selective replicating adenovirus ZD55-IL-24 led to caspase-3 denitrosylation and subsequent activation, indicating that caspase-3 denitrosylation played a crucial role in ZD55-IL-24-induced cancer cell apoptosis. To confirm the relationship between caspase-3 denitrosylation and its activation in response to ZD55-IL-24, we treated carcinoma cells with the different nitric oxide (NO) regulators to modulate caspase-3 denitrosylation level, then observed the corresponding caspase-3 cleavage. We found that NO inhibitor 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO) promoted caspase-3 denitrosylation and caspase-3 cleavage, thereby exacerbating ZD55-IL-24-induced cancer cell apoptosis, whereas NO donor sodium nitroprusside (SNP) showed the opposite effect. Moreover, caspase-3 denitrosylation facilitated its downstream target poly ADP-ribose polymerase (PARP) degradation that further increased the apoptotic susceptibility. Although caspase-3 activation controlled by denitrosylation modification has emerged as an important regulator of programmed cell death, the detailed molecular mechanism by which caspase-3 exerts its denitrosylation modification in response to ZD55-IL-24 still needs to be elucidated. Thus, our results demonstrated that ZD55-IL-24 increased Fas expression to enhance thioredoxin reductase 2 (TrxR2), which was responsible for caspase-3 denitrosylation. Collectively, these findings elucidate that ZD55-IL-24 induces caspase-3 denitrosylation through Fas-mediated TrxR2 enhancement, thereby facilitating caspase-3 cleavage and the downstream caspase signaling pathway activation, which provides a novel insight into ZD55-IL-24-induced cancer-specific apoptosis by post-translational modification of the apoptotic executor caspase-3.

Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice

PubMed Central

Shearn, Colin T.; Fritz, Kristofer S.; Shearn, Alisabeth H.; Saba, Laura M.; Mercer, Kelly E.; Engi, Bridgette; Galligan, James J.; Zimniak, Piotr; Orlicky, David J.; Ronis, Martin J.; Petersen, Dennis R.

2015-01-01

Chronic alcohol consumption induces hepatic oxidative stress resulting in production of highly reactive electrophilic α/β-unsaturated aldehydes that have the potential to modify proteins. A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH. Given reports that oxidative stress initiates GSTA4 translocation to the mitochondria, we hypothesized that increased hepatocellular damage in ethanol (EtOH)-fed GSTA4−/− mice is due to enhanced mitochondrial protein modification by reactive aldehydes. Chronic ingestion of EtOH increased hepatic protein carbonylation in GSTA4−/− mice as evidenced by increased 4-HNE and MDA immunostaining in the hepatic periportal region. Using mass spectrometric analysis of biotin hydrazide conjugated carbonylated proteins, a total of 829 proteins were identified in microsomal, cytosolic and mitochondrial fractions. Of these, 417 were novel to EtOH models. Focusing on mitochondrial fractions, 1.61-fold more carbonylated proteins were identified in EtOH-fed GSTA4−/− mice compared to their respective WT mice ingesting EtOH. Bioinformatic KEGG pathway analysis of carbonylated proteins from the mitochondrial fractions revealed an increased propensity for modification of proteins regulating oxidative phosphorylation, glucose, fatty acid, glutathione and amino acid metabolic processes in GSTA4−/− mice. Additional analysis revealed sites of reactive aldehyde protein modification on 26 novel peptides/proteins isolated from either SV/GSTA4−/− PF or EtOH fed mice. Among the peptides/proteins identified, ACSL, ACOX2, MTP, and THIKB contribute to regulation of fatty acid metabolism and ARG1, ARLY, and OAT, which regulate nitrogen and ammonia metabolism having direct relevance to ethanol-induced liver injury. These data define a role for GSTA4-4 in buffering hepatic oxidative stress associated with chronic alcohol consumption and that this GST isoform plays an important role in protecting against carbonylation of mitochondrial proteins. PMID:26654979

International Workshop on Ion Beam Modification and Processing of High Tc- Superconductors: Physics and Devices: Program and Abstracts

DTIC Science & Technology

1989-04-12

Karlsruhe, FRG The application of ion beams with energies in the region of about 0.3 to 3 MeV for the analysis and modification of superconductors is...Jolla Ca- lifornia 92093, USA It is now well cstablished that the oxygen content and ordering plays a crucial role ih thie transport and crystallographic...the Belgian F.K.F.O., C.V.l{. is a Reserch Associate of the Belian N.F.W.O. I I I I I IRRADIATION INDUCED DEPAIRING IN YBACUO J. Lesueur, P Nddtlec

Determination of copper binding in Pseudomonas putida CZ1 by chemical modifications and X-ray absorption spectroscopy.

PubMed

Chen, XinCai; Shi, JiYan; Chen, YingXu; Xu, XiangHua; Chen, LiTao; Wang, Hui; Hu, TianDou

2007-03-01

Previously performed studies have shown that Pseudomonas putida CZ1 biomass can bind an appreciable amount of Cu(II) and Zn(II) ions from aqueous solutions. The mechanisms of Cu- and Zn-binding by P. putida CZ1 were ascertained by chemical modifications of the biomass followed by Fourier transform infrared and X-ray absorption spectroscopic analyses of the living or nonliving cells. A dramatic decrease in Cu(II)- and Zn(II)-binding resulted after acidic methanol esterification of the nonliving cells, indicating that carboxyl functional groups play an important role in the binding of metal to the biomaterial. X-ray absorption spectroscopy was used to determine the speciation of Cu ions bound by living and nonliving cells, as well as to elucidate which functional groups were involved in binding of the Cu ions. The X-ray absorption near-edge structure spectra analysis showed that the majority of the Cu was bound in both samples as Cu(II). The fitting results of Cu K-edge extended X-ray absorption fine structure spectra showed that N/O ligands dominated in living and nonliving cells. Therefore, by combining different techniques, our results indicate that carboxyl functional groups are the major ligands responsible for the metal binding in P. putida CZ1.

In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae

PubMed Central

Kurotani, Atsushi; Sakurai, Tetsuya

2015-01-01

Recent proteome analyses have reported that intrinsically disordered regions (IDRs) of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs) has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reported. Here, we describe correlations between IDR content and the number of PTM sites for phosphorylation, glycosylation, and ubiquitination, and between IDR content and regions rich in proline, glutamic acid, serine, and threonine (PEST) and transmembrane helices in the sequences of 20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST preferentially occurred in disordered regions. In contrast, transmembrane helices were favored in ordered regions. N-glycosylation tended to occur in ordered regions in most of the studied algae; however, it correlated positively with disordered protein content in diatoms. Additionally, we observed that disordered protein content and the number of PTM sites were significantly increased in the species-specific protein clusters compared to common protein clusters among the algae. Moreover, there were specific relationships between IDRs and PTMs among the algae from different groups. PMID:26307970

In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae.

PubMed

Kurotani, Atsushi; Sakurai, Tetsuya

2015-08-20

Recent proteome analyses have reported that intrinsically disordered regions (IDRs) of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs) has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reported. Here, we describe correlations between IDR content and the number of PTM sites for phosphorylation, glycosylation, and ubiquitination, and between IDR content and regions rich in proline, glutamic acid, serine, and threonine (PEST) and transmembrane helices in the sequences of 20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST preferentially occurred in disordered regions. In contrast, transmembrane helices were favored in ordered regions. N-glycosylation tended to occur in ordered regions in most of the studied algae; however, it correlated positively with disordered protein content in diatoms. Additionally, we observed that disordered protein content and the number of PTM sites were significantly increased in the species-specific protein clusters compared to common protein clusters among the algae. Moreover, there were specific relationships between IDRs and PTMs among the algae from different groups.

Heterogeneity in the Relationship between Disinfection By-Products in Drinking Water and Cancer: A Systematic Review.

PubMed

Benmarhnia, Tarik; Delpla, Ianis; Schwarz, Lara; Rodriguez, Manuel J; Levallois, Patrick

2018-05-14

The epidemiological evidence demonstrating the effect of disinfection by-products (DBPs) from drinking water on colon and rectal cancers is well documented. However, no systematic assessment has been conducted to assess the potential effect measure modification (EMM) in the relationship between DBPs and cancer. The objective of this paper is to conduct a systematic literature review to determine the extent to which EMM has been assessed in the relationship between DBPs in drinking water in past epidemiological studies. Selected articles ( n = 19) were reviewed, and effect estimates and covariates that could have been used in an EMM assessment were gathered. Approximately half of the studies assess EMM ( n = 10), but the majority of studies only estimate it relative to sex subgroups ( n = 6 for bladder cancer and n = 2 both for rectal and colon cancers). Although EMM is rarely assessed, several variables that could have a potential modification effect are routinely collected in these studies, such as socioeconomic status or age. The role of environmental exposures through drinking water can play an important role and contribute to cancer disparities. We encourage a systematic use of subgroup analysis to understand which populations or territories are more vulnerable to the health impacts of DBPs.

DNA interactions of antitumor cisplatin analogs containing enantiomeric amine ligands.

PubMed Central

Malina, J; Hofr, C; Maresca, L; Natile, G; Brabec, V

2000-01-01

Modifications of natural DNA and synthetic oligodeoxyribonucleotide duplexes in a cell-free medium by analogs of antitumor cisplatin containing enantiomeric amine ligands, such as cis-[PtCl(2)(RR-DAB)] and cis-[PtCl(2)(SS-DAB)] (DAB = 2,3-diaminobutane), were studied by various methods of molecular biophysics and biophysical chemistry. These methods include DNA binding studies by pulse polarography and atomic absorption spectrophotometry, mapping of DNA adducts using transcription assay, interstrand cross-linking assay using gel electrophoresis under denaturing conditions, differential scanning calorimetry, chemical probing, and bending and unwinding studies of the duplexes containing single, site-specific cross-link. The major differences resulting from the modification of DNA by the two enantiomers are the thermodynamical destabilization and conformational distortions induced in DNA by the 1,2-d(GpG) intrastrand cross-link. It has been suggested that these differences are associated with a different biological activity of the two enantiomers observed previously. In addition, the results of the present work are also consistent with the view that formation of hydrogen bonds between the carbonyl oxygen of the guanine residues and the "quasi equatorial" hydrogen of the cis amine in the 1, 2-d(GpG) intrastrand cross-link plays an important role in determining the character of the distortion induced in DNA by this lesion. PMID:10733979

Nonhistone protein acetylation as cancer therapy targets

PubMed Central

Singh, Brahma N; Zhang, Guanghua; Hwa, Yi L; Li, Jinping; Dowdy, Sean C; Jiang, Shi-Wen

2012-01-01

Acetylation and deacetylation are counteracting, post-translational modifications that affect a large number of histone and nonhistone proteins. The significance of histone acetylation in the modification of chromatin structure and dynamics, and thereby gene transcription regulation, has been well recognized. A steadily growing number of nonhistone proteins have been identified as acetylation targets and reversible lysine acetylation in these proteins plays an important role(s) in the regulation of mRNA stability, protein localization and degradation, and protein–protein and protein–DNA interactions. The recruitment of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation, differentiation and apoptosis. Many nonhistone proteins targeted by acetylation are the products of oncogenes or tumor-suppressor genes and are directly involved in tumorigenesis, tumor progression and metastasis. Aberrant activity of HDACs has been documented in several types of cancers and HDAC inhibitors (HDACi) have been employed for therapeutic purposes. Here we review the published literature in this field and provide updated information on the regulation and function of nonhistone protein acetylation. While concentrating on the molecular mechanism and pathways involved in the addition and removal of the acetyl moiety, therapeutic modalities of HDACi are also discussed. PMID:20553216

The Deep Thioredoxome in Chlamydomonas reinhardtii: New Insights into Redox Regulation.

PubMed

Pérez-Pérez, María Esther; Mauriès, Adeline; Maes, Alexandre; Tourasse, Nicolas J; Hamon, Marion; Lemaire, Stéphane D; Marchand, Christophe H

2017-08-07

Thiol-based redox post-translational modifications have emerged as important mechanisms of signaling and regulation in all organisms, and thioredoxin plays a key role by controlling the thiol-disulfide status of target proteins. Recent redox proteomic studies revealed hundreds of proteins regulated by glutathionylation and nitrosylation in the unicellular green alga Chlamydomonas reinhardtii, while much less is known about the thioredoxin interactome in this organism. By combining qualitative and quantitative proteomic analyses, we have comprehensively investigated the Chlamydomonas thioredoxome and 1188 targets have been identified. They participate in a wide range of metabolic pathways and cellular processes. This study broadens not only the redox regulation to new enzymes involved in well-known thioredoxin-regulated metabolic pathways but also sheds light on cellular processes for which data supporting redox regulation are scarce (aromatic amino acid biosynthesis, nuclear transport, etc). Moreover, we characterized 1052 thioredoxin-dependent regulatory sites and showed that these data constitute a valuable resource for future functional studies in Chlamydomonas. By comparing this thioredoxome with proteomic data for glutathionylation and nitrosylation at the protein and cysteine levels, this work confirms the existence of a complex redox regulation network in Chlamydomonas and provides evidence of a tremendous selectivity of redox post-translational modifications for specific cysteine residues. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Heterogeneity in the Relationship between Disinfection By-Products in Drinking Water and Cancer: A Systematic Review

PubMed Central

Delpla, Ianis; Schwarz, Lara; Rodriguez, Manuel J.; Levallois, Patrick

2018-01-01

The epidemiological evidence demonstrating the effect of disinfection by-products (DBPs) from drinking water on colon and rectal cancers is well documented. However, no systematic assessment has been conducted to assess the potential effect measure modification (EMM) in the relationship between DBPs and cancer. The objective of this paper is to conduct a systematic literature review to determine the extent to which EMM has been assessed in the relationship between DBPs in drinking water in past epidemiological studies. Selected articles (n = 19) were reviewed, and effect estimates and covariates that could have been used in an EMM assessment were gathered. Approximately half of the studies assess EMM (n = 10), but the majority of studies only estimate it relative to sex subgroups (n = 6 for bladder cancer and n = 2 both for rectal and colon cancers). Although EMM is rarely assessed, several variables that could have a potential modification effect are routinely collected in these studies, such as socioeconomic status or age. The role of environmental exposures through drinking water can play an important role and contribute to cancer disparities. We encourage a systematic use of subgroup analysis to understand which populations or territories are more vulnerable to the health impacts of DBPs. PMID:29757939

Novel use of residue from direct coal liquefaction process

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

Jianli Yang; Zhaixia Wang; Zhenyu Liu

2009-09-15

Direct coal liquefaction residue (DCLR) is, commonly, designed to be used as a feed stock for gasification or combustion. Use of DCLR as a value added product is very important for improving overall economy of direct coal liquefaction processes. This study shows that the DCLR may be used as a pavement asphalt modifier. The modification ability is similar to that of Trinidad Lake Asphalt (TLA), a superior commercial modifier. Asphalts modified by two DCLRs meet the specifications of ASTM D5710 and BSI BS-3690 designated for the TLA-modified asphalts. The required addition amount for the DCLRs tested is less than thatmore » for TLA due possibly to the high content of asphaltene in DCLRs. Different compatibility was observed for the asphalts with the same penetration grade but from the different origin. Different components in the DCLR play different roles in the modification. Positive synergetic effects among the fractions were observed, which may due to the formation of the stable colloid structure. Unlike polymer-type modifier, the structure of asphalt-type modifier has a similarity with petroleum asphalts which favors the formation of a stable dispersed polar fluid (DPF) colloid structure and improves the performance of pavement asphalt. 12 refs., 1 fig., 6 tabs.« less

Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer.

PubMed

Abdel-Hafiz, Hany A

2017-07-06

Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics.

Interaction of gold and silver nanoparticles with human plasma: Analysis of protein corona reveals specific binding patterns.

PubMed

Lai, Wenjia; Wang, Qingsong; Li, Lumeng; Hu, Zhiyuan; Chen, Jiankui; Fang, Qiaojun

2017-04-01

Determining how nanomaterials interact with plasma will assist in understanding their effects on the biological system. This work presents a systematic study of the protein corona formed from human plasma on 20nm silver and gold nanoparticles with three different surface modifications, including positive and negative surface charges. The results show that all nanoparticles, even those with positive surface modifications, acquire negative charges after interacting with plasma. Approximately 300 proteins are identified on the coronas, while 99 are commonly found on each nanomaterial. The 20 most abundant proteins account for over 80% of the total proteins abundance. Remarkably, the surface charge and core of the nanoparticles, as well as the isoelectric point of the plasma proteins, are found to play significant roles in determining the nanoparticle coronas. Albumin and globulins are present at levels of less than 2% on these nanoparticle coronas. Fibrinogen, which presents in the plasma but not in the serum, preferably binds to negatively charged gold nanoparticles. These observations demonstrate the specific plasma protein binding pattern of silver and gold nanoparticles, as well as the importance of the surface charge and core in determining the protein corona compositions. The potential downstream biological impacts of the corona proteins were also investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of vision on masticatory muscles function: surface electromyographic evaluation

PubMed Central

Ciavarella, Domenico; Palazzo, Antonio; De Lillo, Alfredo; Lo Russo, Lucio; Paduano, Sergio; Laino, Luigi; Chimenti, Claudio; Frezza, Federica; Lo Muzio, Lorenzo

2014-01-01

Summary The role of the ocular disorders (OD) in pathogenesis of MMp is still a controversal issue. Ocular arc reflexes (OAR) may involve changes in head and neck posture and generate modifications of contraction resulting in muscle contraction and finally weakness. sEMG tests were performed on 28 patients (13 with masticatory muscles pain and myopia/15 healthy) in rest position with eyes open and eyes closed. Patients group control (healthy patients) showed no significance difference in sEMG record in open/close test. In non healthy patients there were great differences between the sEMG recordings with eyes closed and open. Temporalis and masseters showed a statistical difference of means activation in two tests (temporalis p = 0.0010; masseters = 0.0006). Great difference there was in means muscles activation between open eyes healthy test and non healthy. No difference in close eyes test was evaluated in temporalis and masseters close test in the two groups. The exact causes of MMp are still unknown. The role how ocular disorders (OD) may play an important role in pathogenesis of MMp is still a controversal issue. Ocular arc reflexes (OAR) may involve changes in head and neck posture and generate modifications of contraction resulting in muscle contraction and finally weakness. PMID:25002919

Perilla Oil Has Similar Protective Effects of Fish Oil on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Gut Dysbiosis.

PubMed

Tian, Yu; Wang, Hualin; Yuan, Fahu; Li, Na; Huang, Qiang; He, Lei; Wang, Limei; Liu, Zhiguo

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries. Recent studies indicated that the modification of gut microbiota plays an important role in the progression from simple steatosis to steatohepatitis. Epidemiological studies have demonstrated consumption of fish oil or perilla oil rich in n-3 polyunsaturated fatty acids (PUFAs) protects against NAFLD. However, the underlying mechanisms remain unclear. In the present study, we adopted 16s rRNA amplicon sequencing technique to investigate the impacts of fish oil and perilla oil on gut microbiomes modification in rats with high-fat diet- (HFD-) induced NAFLD. Both fish oil and perilla oil ameliorated HFD-induced hepatic steatosis and inflammation. In comparison with the low-fat control diet, HFD feeding significantly reduced the relative abundance of Gram-positive bacteria in the gut, which was slightly reversed by either fish oil or perilla oil. Additionally, fish oil and perilla oil consumption abrogated the elevated abundance of Prevotella and Escherichia in the gut from HFD fed animals. Interestingly, the relative abundance of antiobese Akkermansia was remarkably increased only in animals fed fish oil compared with HFD group. In conclusion, compared with fish oil, perilla oil has similar but slightly weaker potency against HFD-induced NAFLD and gut dysbiosis.

novPTMenzy: a database for enzymes involved in novel post-translational modifications

PubMed Central

Khater, Shradha; Mohanty, Debasisa

2015-01-01

With the recent discoveries of novel post-translational modifications (PTMs) which play important roles in signaling and biosynthetic pathways, identification of such PTM catalyzing enzymes by genome mining has been an area of major interest. Unlike well-known PTMs like phosphorylation, glycosylation, SUMOylation, no bioinformatics resources are available for enzymes associated with novel and unusual PTMs. Therefore, we have developed the novPTMenzy database which catalogs information on the sequence, structure, active site and genomic neighborhood of experimentally characterized enzymes involved in five novel PTMs, namely AMPylation, Eliminylation, Sulfation, Hydroxylation and Deamidation. Based on a comprehensive analysis of the sequence and structural features of these known PTM catalyzing enzymes, we have created Hidden Markov Model profiles for the identification of similar PTM catalyzing enzymatic domains in genomic sequences. We have also created predictive rules for grouping them into functional subfamilies and deciphering their mechanistic details by structure-based analysis of their active site pockets. These analytical modules have been made available as user friendly search interfaces of novPTMenzy database. It also has a specialized analysis interface for some PTMs like AMPylation and Eliminylation. The novPTMenzy database is a unique resource that can aid in discovery of unusual PTM catalyzing enzymes in newly sequenced genomes. Database URL: http://www.nii.ac.in/novptmenzy.html PMID:25931459

Emotional intelligence in the workplace: exploring its effects on occupational stress and health outcomes in human service workers.

PubMed

Ogińska-Bulik, Nina

2005-01-01

Emotional intelligence, an essential factor responsible for determining success in life and psychological well-being, seems to play an important role in shaping the interaction between individuals and their work environment. The purpose of the study was to explore the relationship between emotional intelligence and perceived stress in the workplace and health-related consequences in human service workers. A sample of 330 participants (42.4% of men and 57.6% of women), representing various human service professions (physicians, nurses, teachers, probation officers and managers) was eligible for the study. The mean age of the participants was 38.4 years (SD = 8.45), and the employment period was 8.3 years (SD = 6.13). Three methods were used in the study: The Emotional Intelligence Questionnaire--INTE with Polish modification, the Subjective Work Evaluation Questionnaire developed in Poland, and the General Health Questionnaire (GHQ-28) with Polish modification. The results confirmed an essential, but not very strong, role of emotional intelligence in perceiving occupational stress and preventing employees of human services from negative health outcomes. The ability to effectively deal with emotions and emotional information in the workplace assists employees in coping with occupational stress therefore, it should be developed in stress managing trainings.

Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

PubMed Central

Wen, Xingxing; Ding, Shan; Cai, Hui; Wang, Junyi; Wen, Lu; Yang, Fan; Chen, Gang

2016-01-01

Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy. PMID:27877041

Foetoplacental epigenetic changes associated with maternal metabolic dysfunction.

PubMed

Kerr, Bredford; Leiva, Andrea; Farías, Marcelo; Contreras-Duarte, Susana; Toledo, Fernando; Stolzenbach, Francisca; Silva, Luis; Sobrevia, Luis

2018-04-12

Metabolic-related diseases are attributed to a sedentary lifestyle and eating habits, and there is now an increased awareness regarding pregnancy as a preponderant window in the programming of adulthood health and disease. The developing foetus is susceptible to the maternal environment; hence, any unfavourable condition will result in foetal physiological adaptations that could have a permanent impact on its health. Some of these alterations are maintained via epigenetic modifications capable of modifying gene expression in metabolism-related genes. Children born to mothers with dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus, have a predisposition to develop metabolic alterations during adulthood. CpG methylation-associated alterations to the expression of several genes in the human placenta play a crucial role in the mother-to-foetus transfer of nutrients and macromolecules. Identification of epigenetic modifications in metabolism-related tissues of offspring from metabolic-altered pregnancies is essential to obtain insights into foetal programming controlling newborn, childhood, and adult metabolism. This review points out the importance of the foetal milieu in the programming and development of human disease and provides evidence of this being the underlying mechanism for the development of adulthood metabolic disorders in maternal dyslipidaemia, pregestational or gestational obesity, and gestational diabetes mellitus. Copyright © 2018. Published by Elsevier Ltd.

Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human ovarian granulosa cell line.

PubMed

Wu, Yimin; Lu, Yunzhe; Hu, Yanfen; Li, Rong

2005-11-01

In response to gonadotropins, the elevated level of intracellular-cyclic AMP (cAMP) in ovarian granulosa cells triggers an ordered activation of multiple ovarian genes, which in turn promotes various ovarian functions including folliculogenesis and steroidogenesis. Identification and characterization of transcription factors that control ovarian gene expression are pivotal to the understanding of the molecular basis of the tissue-specific gene regulation programs. The recent discovery of the mouse TATA binding protein (TBP)-associated factor 105 (TAF(II)105) as a gonad-selective transcriptional co-activator strongly suggests that general transcription factors such as TFIID may play a key role in regulating tissue-specific gene expression. Here we show that the human TAF(II)105 protein is preferentially expressed in ovarian granulosa cells. We also identified a novel TAF(II)105 mRNA isoform that results from alternative exon inclusion and is predicted to encode a dominant negative mutant of TAF(II)105. Following stimulation by the adenylyl cyclase activator forskolin, TAF(II)105 in granulosa cells undergoes rapid and transient phosphorylation that is dependent upon protein kinase A (PKA). Thus, our work suggests that pre-mRNA processing and post-translational modification represent two important regulatory steps for the gonad-specific functions of human TAF(II)105. Copyright 2005 Wiley-Liss, Inc.

Steady and dynamic shear rheological properties of gum-based food thickeners used for diet modification of patients with dysphagia: effect of concentration.

PubMed

Seo, Chan-Won; Yoo, Byoungseung

2013-06-01

Gum-based food thickeners are widely used for diet modification for patients with dysphagia in Korea. In this study, the rheological properties of two commercially available gum-based food thickeners (xanthan gum and xanthan-guar gum mixture) marketed in Korea were determined as a function of concentration. The steady and dynamic shear rheological properties of the food thickeners in water were investigated at five different concentrations (1.0 %, 1.5 %, 2.0 %, 2.5 %, and 3.0 % w/w). Both food thickeners showed high shear-thinning fluid characteristics (n = 0.14-0.19) at all concentrations (1.0-3.0 %). In general, the thickener with the xanthan-guar gum mixture showed higher values for steady shear viscosity compared to that with xanthan alone, whereas it showed lower dynamic rheological parameter values. Steady and dynamic rheological parameters demonstrated differences in rheological behaviors between the gum-based food thickeners, indicating that their rheological properties are related to the type of gum and gum concentration. In particular, the type of gum played a role in the time-dependent flow properties of the gum-based food thickeners. Appropriately selecting a commercial food thickener appears to be of great importance for dysphagia therapists and patients.

Epigenetic regulation in dental pulp inflammation

PubMed Central

Hui, T; Wang, C; Chen, D; Zheng, L; Huang, D; Ye, L

2016-01-01

Dental caries, trauma, and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis. PMID:26901577

Mechanical Waves Conceptual Survey: Its Modification and Conversion to a Standard Multiple-Choice Test

ERIC Educational Resources Information Center

Barniol, Pablo; Zavala, Genaro

2016-01-01

In this article we present several modifications of the mechanical waves conceptual survey, the most important test to date that has been designed to evaluate university students' understanding of four main topics in mechanical waves: propagation, superposition, reflection, and standing waves. The most significant changes are (i) modification of…

Yeast One-Hybrid Gγ Recruitment System for Identification of Protein Lipidation Motifs

PubMed Central

Fukuda, Nobuo; Doi, Motomichi; Honda, Shinya

2013-01-01

Fatty acids and isoprenoids can be covalently attached to a variety of proteins. These lipid modifications regulate protein structure, localization and function. Here, we describe a yeast one-hybrid approach based on the Gγ recruitment system that is useful for identifying sequence motifs those influence lipid modification to recruit proteins to the plasma membrane. Our approach facilitates the isolation of yeast cells expressing lipid-modified proteins via a simple and easy growth selection assay utilizing G-protein signaling that induces diploid formation. In the current study, we selected the N-terminal sequence of Gα subunits as a model case to investigate dual lipid modification, i.e., myristoylation and palmitoylation, a modification that is widely conserved from yeast to higher eukaryotes. Our results suggest that both lipid modifications are required for restoration of G-protein signaling. Although we could not differentiate between myristoylation and palmitoylation, N-terminal position 7 and 8 play some critical role. Moreover, we tested the preference for specific amino-acid residues at position 7 and 8 using library-based screening. This new approach will be useful to explore protein-lipid associations and to determine the corresponding sequence motifs. PMID:23922919

Coordinated action of histone modification and microRNA regulations in human genome.

PubMed

Wang, Xuan; Zheng, Guantao; Dong, Dong

2015-10-10

Both histone modifications and microRNAs (miRNAs) play pivotal role in gene expression regulation. Although numerous studies have been devoted to explore the gene regulation by miRNA and epigenetic regulations, their coordinated actions have not been comprehensively examined. In this work, we systematically investigated the combinatorial relationship between miRNA and epigenetic regulation by taking advantage of recently published whole genome-wide histone modification data and high quality miRNA targeting data. The results showed that miRNA targets have distinct histone modification patterns compared with non-targets in their promoter regions. Based on this finding, we proposed a machine learning approach to fit predictive models on the task to discern whether a gene is targeted by a specific miRNA. We found a considerable advantage in both sensitivity and specificity in diverse human cell lines. Finally, we found that our predicted miRNA targets are consistently annotated with Gene Ontology terms. Our work is the first genome-wide investigation of the coordinated action of miRNA and histone modification regulations, which provide a guide to deeply understand the complexity of transcriptional regulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells

PubMed Central

King, Sarah L.; Joshi, Hiren J.; Schjoldager, Katrine T.; Halim, Adnan; Madsen, Thomas D.; Dziegiel, Morten H.; Woetmann, Anders; Vakhrushev, Sergey Y.

2017-01-01

The hemostatic system comprises platelet aggregation, coagulation, and fibrinolysis, and is critical to the maintenance of vascular integrity. Multiple studies indicate that glycans play important roles in the hemostatic system; however, most investigations have focused on N-glycans because of the complexity of O-glycan analysis. Here we performed the first systematic analysis of native-O-glycosylation using lectin affinity chromatography coupled to liquid chromatography mass spectrometry (LC-MS)/MS to determine the precise location of O-glycans in human plasma, platelets, and endothelial cells, which coordinately regulate hemostasis. We identified the hitherto largest O-glycoproteome from native tissue with a total of 649 glycoproteins and 1123 nonambiguous O-glycosites, demonstrating that O-glycosylation is a ubiquitous modification of extracellular proteins. Investigation of the general properties of O-glycosylation established that it is a heterogeneous modification, frequently occurring at low density within disordered regions in a cell-dependent manner. Using an unbiased screen to identify associations between O-glycosites and protein annotations we found that O-glycans were over-represented close (± 15 amino acids) to tandem repeat regions, protease cleavage sites, within propeptides, and located on a select group of protein domains. The importance of O-glycosites in proximity to proteolytic cleavage sites was further supported by in vitro peptide assays demonstrating that proteolysis of key hemostatic proteins can be inhibited by the presence of O-glycans. Collectively, these data illustrate the global properties of native O-glycosylation and provide the requisite roadmap for future biomarker and structure-function studies. PMID:29296958

Protein phosphorylation in plant immunity: insights into the regulation of pattern recognition receptor-mediated signaling

PubMed Central

Park, Chang-Jin; Caddell, Daniel F.; Ronald, Pamela C.

2012-01-01

Plants are continuously challenged by pathogens including viruses, bacteria, and fungi. The plant immune system recognizes invading pathogens and responds by activating an immune response. These responses occur rapidly and often involve post-translational modifications (PTMs) within the proteome. Protein phosphorylation is a common and intensively studied form of these PTMs and regulates many plant processes including plant growth, development, and immunity. Most well-characterized pattern recognition receptors (PRRs), including Xanthomonas resistance 21, flagellin sensitive 2, and elongation factor-Tu receptor, possess intrinsic protein kinase activity and regulate downstream signaling through phosphorylation events. Here, we focus on the phosphorylation events of plant PRRs that play important roles in the immune response. We also discuss the role of phosphorylation in regulating mitogen-associated protein kinase cascades and transcription factors in plant immune signaling. PMID:22876255

Developments in pesticide packaging and management of bulk herbicides as elements in a container reduction strategy

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

Bradley, D.

Pesticide packaging plays an important role in a broader area that can be called {open_quotes}Delivery Systems.{close_quotes} Delivery Systems can include all of the physical elements that enable a technical active ingredient or combination of ingredients to move from the manufacturing plant through the channels of distribution to the pesticide applicator, who generally further dilutes the product for use on a registered target pest or crop site. This article describes developments relating to three goals in pesticide packaging. Those goals are: reduction in the number of empty containers through the use of reusable containers, formulation modifications, and other container minimization approaches;more » recyling of empty containers for their material or energy value; and disposal of empty containers in accordance with environmentally sound and cost effective practices.« less

4H-SiC surface energy tuning by nitrogen up-take

NASA Astrophysics Data System (ADS)

Pitthan, E.; Amarasinghe, V. P.; Xu, C.; Gustafsson, T.; Stedile, F. C.; Feldman, L. C.

2017-04-01

Surface energy modification and surface wettability of 4H silicon carbide (0001) as a function of nitrogen adsorption is reported. The surface wettability is shown to go from primarily hydrophilic to hydrophobic and the surface energy was significantly reduced with increasing nitrogen incorporation. These changes are investigated by x-ray photoelectron spectroscopy and contact angle measurements. The surface energy was quantitatively determined by the Fowkes model and interpreted primarily in terms of the variation of the surface chemistry with nitrogen coverage. Variable control of SiC surface energies with a simple and controllable atomic additive such as nitrogen that is inert to etching, stable against time, and also effective in electrical passivation, can provide new opportunities for SiC biomedical applications, where surface wetting plays an important role in the interaction with the biological interfaces.

Tumor purity and differential methylation in cancer epigenomics.

PubMed

Wang, Fayou; Zhang, Naiqian; Wang, Jun; Wu, Hao; Zheng, Xiaoqi

2016-11-01

DNA methylation is an epigenetic modification of DNA molecule that plays a vital role in gene expression regulation. It is not only involved in many basic biological processes, but also considered an important factor for tumorigenesis and other human diseases. Study of DNA methylation has been an active field in cancer epigenomics research. With the advances of high-throughput technologies and the accumulation of enormous amount of data, method development for analyzing these data has gained tremendous interests in the fields of computational biology and bioinformatics. In this review, we systematically summarize the recent developments of computational methods and software tools in high-throughput methylation data analysis with focus on two aspects: differential methylation analysis and tumor purity estimation in cancer studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The "sweet" side of the protein corona: effects of glycosylation on nanoparticle-cell interactions.

PubMed

Wan, Sha; Kelly, Philip M; Mahon, Eugene; Stöckmann, Henning; Rudd, Pauline M; Caruso, Frank; Dawson, Kenneth A; Yan, Yan; Monopoli, Marco P

2015-02-24

The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle-cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle-cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle-cell interactions by modulating the protein corona properties.

Androgen receptor-related diseases: what do we know?

PubMed

Shukla, G C; Plaga, A R; Shankar, E; Gupta, S

2016-05-01

The androgen receptor (AR) and the androgen-AR signaling pathway play a significant role in male sexual differentiation and the development and function of male reproductive and non-reproductive organs. Because of AR's widely varied and important roles, its abnormalities have been identified in various diseases such as androgen insensitivity syndrome, spinal bulbar muscular atrophy, benign prostatic hyperplasia, and prostate cancer. This review provides an overview of the function of androgens and androgen-AR mediated diseases. In addition, the diseases delineated above are discussed with respect to their association with mutations and other post-transcriptional modifications in the AR. Finally, we present an introduction to the potential therapeutic application of most recent pharmaceuticals including miRNAs in prostate cancer that specifically target the transactivation function of the AR at post-transcriptional stages. © 2016 American Society of Andrology and European Academy of Andrology.

Colour change evaluation on UV radiation exposure for Păun-Repedea calcareous geomaterial

NASA Astrophysics Data System (ADS)

Pelin, V.; Sandu, I.; Munteanu, M.; Iurcovschi, C. T.; Gurlui, S.; Sandu, AV; Vasilache, V.; Brȃnzilă, M.; Sandu, I. G.

2016-06-01

When talking about the preservation treatments that can be applied to natural stones used in different constructions, the surface hydrophobization plays an important part, especially when referring to porous surfaces like the calcareous oolithic stones specific to Repedea area, Iasi County, Romania. The present paper presents a method that evaluates the hydrophobization efficiency of two types of pellicles, involving UV artificial ageing and colorimetric analysis of the treated surfaces. The evaluation was done through continuous colorimetric monitoring and by comparing the evolution of the chromatic modifications of the two treated surfaces with the original colorimetric values and with the witness area, which was exposed to UV radiations under the same conditions, but left chemical untreated. The techniques used during this experiment were: CIE L*a*b* colorimetry, OM, SEM-EDX, UV radiation exposure and Spectrum Irradiance Measurement.

Epigenetics of prostate cancer.

PubMed

Li, Long-Cheng

2007-05-01

Prostate cancer is the most common type of cancer other than skin cancer and the second leading cause of cancer death in men in the United States. Its exact causes are unknown. Several risk factors have been associated with prostate cancer including age, race, family history and diet. Epigenetic mechanisms including DNA methylation and histone modifications are important means of gene regulation and play essential roles in diverse biological and disease processes. Recently, frequent epigenetic aberrations such as DNA hypo- and hypermethylation and altered histone acetylation and methylation have been observed in prostate cancer affecting the expression and function of a large array of genes, leading to tumorigenesis, tumor progression and metastasis. In this chapter, we examined the current literature regarding epigenetic changes in prostate cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.

Mutation induction by heavy ions

NASA Astrophysics Data System (ADS)

Kiefer, J.; Stoll, U.; Schneider, E.

1994-10-01

Mutation induction by heavy ions is compared in yeast and mammalian cells. Since mutants can only be recovered in survivors the influence of inactivation cross sections has to be taken into account. It is shown that both the size of the sensitive cellular site as well as track structure play an important role. Another parameter which influences the probability of mutation induction is repair: Contrary to naive assumptions primary radiation damage does not directly lead to mutations but requires modification to reconstitute the genetic machinery so that mutants can survive. The molecular structure of mutations was analyzed after exposure to deuterons by amplification with the aid of polymerase chain reaction. The results-although preliminary-demonstrate that even with densely ionizing particles a large fraction does not carry big deletions which suggests that point mutations may also be induced by heavy ions.

Analysis of noise in quorum sensing.

PubMed

Cox, Chris D; Peterson, Gregory D; Allen, Michael S; Lancaster, Joseph M; McCollum, James M; Austin, Derek; Yan, Ling; Sayler, Gary S; Simpson, Michael L

2003-01-01

Noise may play a pivotal role in gene circuit functionality, as demonstrated for the genetic switch in the bacterial phage lambda. Like the lambda switch, bacterial quorum sensing (QS) systems operate within a population and contain a bistable switching element, making it likely that noise plays a functional role in QS circuit operation. Therefore, a detailed analysis of the noise behavior of QS systems is needed. We have developed a set of tools generally applicable to the analysis of gene circuits, with an emphasis on investigations in the frequency domain (FD), that we apply here to the QS system in the marine bacterium Vibrio fischeri. We demonstrate that a tight coupling between exact stochastic simulation and FD analysis provides insights into the structure/function relationships in the QS circuit. Furthermore, we argue that a noise analysis is incomplete without consideration of the power spectral densities (PSDs) of the important molecular output signals. As an example we consider reversible reactions in the QS circuit, and show through analysis and exact stochastic simulation that these circuits make significant and dynamic modifications to the noise spectra. In particular, we demonstrate a "whitening" effect, which occurs as the noise is processed through these reversible reactions.

Role of Lipid Metabolism in Plant Pollen Exine Development.

PubMed

Zhang, Dabing; Shi, Jianxin; Yang, Xijia

2016-01-01

Pollen plays important roles in the life cycle of angiosperms plants. It acts as not only a biological protector of male sperms but also a communicator between the male and the female reproductive organs, facilitating pollination and fertilization. Pollen is produced within the anther, and covered by the specialized outer envelope, pollen wall. Although the morphology of pollen varies among different plant species, the pollen wall is mainly comprised of three layers: the pollen coat, the outer exine layer, and the inner intine layer. Except the intine layer, the other two layers are basically of lipidic nature. Particularly, the outer pollen wall layer, the exine, is a highly resistant biopolymer of phenylpropanoid and lipidic monomers covalently coupled by ether and ester linkages. The precise molecular mechanisms underlying pollen coat formation and exine patterning remain largely elusive. Herein, we summarize the current genetic, phenotypic and biochemical studies regarding to the pollen exine development and underlying molecular regulatory mechanisms mainly obtained from monocot rice (Oryza sativa) and dicot Arabidopsis thaliana, aiming to extend our understandings of plant male reproductive biology. Genes, enzymes/proteins and regulatory factors that appear to play conserved and diversified roles in lipid biosynthesis, transportation and modification during pollen exine formation, were highlighted.

A Cognitive-Behavioral Perspective on Intelligence.

ERIC Educational Resources Information Center

Meichenbaum, Donald

1980-01-01

The first purpose of this editorial is to indicate a parallel trend in two disparate areas of research: information processing and cognitive-behavior modification (CBM). The second purpose is to highlight the role that affect plays in intellectual functioning, noting implications following the assessment of intelligence. (Author/RD)

The impacts of lignin modifications on fungal pathogen and insect interactions in sorghum

USDA-ARS?s Scientific Manuscript database

Sorghum (Sorghum bicolor (L.) Moench) is currently being developed as a dedicated bioenergy feedstock. Modifying lignin content and composition are major targets for bioenergy feedstock improvement. However, lignin has long been implicated as playing a critical role in plant defense responses agains...

NAGWS Softball Guide 1991: Official Rules/Officiating.

ERIC Educational Resources Information Center

Matson, Janis

This softball guide presents information on: the National Association for Girls and Women in Sport (NAGWS), rule modifications, softball playing rules, and officiating. Section 1 explains the purpose, beliefs, and services of the NAGWS; provides information on the association's committees and membership application; and explains use of the…

Review of vegetable fermentations with particular emphasis on processing modifications, microbial ecology, and spoilage

USDA-ARS?s Scientific Manuscript database

The consumption of vegetables is widespread in the world and represents a major component of the human diet. Microorganisms (mainly lactic acid bacteria, yeasts, Enterobacteriaceae, Propionibacterium and Clostridium species) play a significant role in vegetable fermentations, affecting the quality a...

Ethylene suppresses tomato (solanum lycopersicum) fruit set through modification of gibberellin metabolism

USDA-ARS?s Scientific Manuscript database

The plant hormone ethylene is probably best know as the “ripening hormone”. Ethylene also plays roles in senescence, stress responses and organ shedding (abscission). Regulation of ethylene synthesis, ethylene scavenging and genetic repression of ethylene synthesis and/or signaling are tactics dep...

Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

PubMed

Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

2008-07-01

Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

Possible End to an Endless Quest? Cognitive Bias Modification for Excessive Multiplayer Online Gamers.

PubMed

Rabinovitz, Sharon; Nagar, Maayan

2015-10-01

Cognitive biases have previously been recognized as key mechanisms that contribute to the development, maintenance, and relapse of addictive behaviors. The same mechanisms have been recently found in problematic computer gaming. The present study aims to investigate whether excessive massively multiplayer online role-playing gamers (EG) demonstrate an approach bias toward game-related cues compared to neutral stimuli; to test whether these automatic action tendencies can be implicitly modified in a single session training; and to test whether this training affects game urges and game-seeking behavior. EG (n=38) were randomly assigned to a condition in which they were implicitly trained to avoid or to approach gaming cues by pushing or pulling a joystick, using a computerized intervention (cognitive bias modification via the Approach Avoidance Task). EG demonstrated an approach bias for gaming cues compared with neutral, movie cues. Single session training significantly decreased automatic action tendencies to approach gaming cues. These effects occurred outside subjective awareness. Furthermore, approach bias retraining reduced subjective urges and intentions to play, as well as decreased game-seeking behavior. Retraining automatic processes may be beneficial in changing addictive impulses in EG. Yet, large-scale trials and long-term follow-up are warranted. The results extend the application of cognitive bias modification from substance use disorders to behavioral addictions, and specifically to Internet gaming disorder. Theoretical implications are discussed.

Albumin modification and fragmentation in renal disease.

PubMed

Donadio, Carlo; Tognotti, Danika; Donadio, Elena

2012-02-18

Albumin is the most important antioxidant substance in plasma and performs many physiological functions. Furthermore, albumin is the major carrier of endogenous molecules and exogenous ligands. This paper reviews the importance of post-translational modifications of albumin and fragments thereof in patients with renal disease. First, current views and controversies on renal handling of proteins, mainly albumin, will be discussed. Post-translational modifications, namely the fragmentation of albumin found with proteomic techniques in nephrotic patients, diabetics, and ESRD patients will be presented and discussed. It is reasonable to hypothesize that proteolytic fragmentation of serum albumin is due to a higher susceptibility to proteases, induced by oxidative stress. The clinical relevance of the fragmentation of albumin has not yet been established. These modifications could affect some physiological functions of albumin and have a patho-physiological role in uremic syndrome. Proteomic analysis of serum allows the identification of over-expressed proteins and can detect post-translational modifications of serum proteins, hitherto hidden, using standard laboratory techniques. Copyright © 2011 Elsevier B.V. All rights reserved.

Provenance information as a tool for addressing engineered nanoparticle reproducibility challenges

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

Baer, Donald R.; Munusamy, Prabhakaran; Thrall, Brian D.

Nanoparticles of various types are of increasing research and technological importance in biological and other applications. Difficulties in the production and delivery of nanoparticles with consistent and well defined properties appear in many forms and have a variety of causes. Among several issues are those associated with incomplete information about the history of particles involved in research studies including the synthesis method, sample history after synthesis including time and nature of storage and the detailed nature of any sample processing or modification. In addition, the tendency of particles to change with time or environmental condition suggests that the time betweenmore » analysis and application is important and some type of consistency or verification process can be important. The essential history of a set of particles can be identified as provenance information tells the origin or source of a batch of nano-objects along with information related to handling and any changes that may have taken place since it was originated. A record of sample provenance information for a set of particles can play a useful role in identifying some of the sources and decreasing the extent of particle variability and the observed lack of reproducibility observed by many researchers.« less

Lignin: Characterization of a Multifaceted Crop Component

PubMed Central

2013-01-01

Lignin is a plant component with important implications for various agricultural disciplines. It confers rigidity to cell walls, and is therefore associated with tolerance to abiotic and biotic stresses and the mechanical stability of plants. In animal nutrition, lignin is considered an antinutritive component of forages as it cannot be readily fermented by rumen microbes. In terms of energy yield from biomass, the role of lignin depends on the conversion process. It contains more gross energy than other cell wall components and therefore confers enhanced heat value in thermochemical processes such as direct combustion. Conversely, it negatively affects biological energy conversion processes such as bioethanol or biogas production, as it inhibits microbial fermentation of the cell wall. Lignin from crop residues plays an important role in the soil organic carbon cycling, as it constitutes a recalcitrant carbon pool affecting nutrient mineralization and carbon sequestration. Due to the significance of lignin in several agricultural disciplines, the modification of lignin content and composition by breeding is becoming increasingly important. Both mapping of quantitative trait loci and transgenic approaches have been adopted to modify lignin in crops. However, breeding goals must be defined considering the conflicting role of lignin in different agricultural disciplines. PMID:24348159

Pelle kinase is activated by autophosphorylation during Toll signaling in Drosophila.

PubMed

Shen, Baohe; Manley, James L

2002-04-01

The Drosophila Pelle kinase plays a key role in the evolutionarily conserved Toll signaling pathway, but the mechanism responsible for its activation has been unknown. We present in vivo and in vitro evidence establishing an important role for concentration-dependent autophosphorylation in the signaling process. We first show that Pelle phosphorylation can be detected transiently in early embryos, concomitant with activation of signaling. Importantly, Pelle phosphorylation is enhanced in a gain-of-function Toll mutant (Toll(10b)), but decreased by loss-of-function Toll alleles. Next we found that Pelle is phosphorylated in transfected Schneider L2 cells in a concentration-dependent manner such that significant modification is observed only at high Pelle concentrations, which coincide with levels required for phosphorylation and activation of the downstream target, Dorsal. Pelle phosphorylation is also enhanced in L2 cells co-expressing Toll(10b), and is dependent on Pelle kinase activity. In vitro kinase assays revealed that recombinant, autophosphorylated Pelle is far more active than unphosphorylated Pelle. Importantly, unphosphorylated Pelle becomes autophosphorylated, and activated, by incubation at high concentrations. We discuss these results in the context of Toll-like receptor mediated signaling in both flies and mammals.

[Advances in microbial genome reduction and modification].

PubMed

Wang, Jianli; Wang, Xiaoyuan

2013-08-01

Microbial genome reduction and modification are important strategies for constructing cellular chassis used for synthetic biology. This article summarized the essential genes and the methods to identify them in microorganisms, compared various strategies for microbial genome reduction, and analyzed the characteristics of some microorganisms with the minimized genome. This review shows the important role of genome reduction in constructing cellular chassis.

Aircraft Modifications: Assessing the Current State of Air Force Aircraft Modifications and the Implications for Future Military Capability

DTIC Science & Technology

2007-01-25

Air, Space , and Cyberspace." Introduction 3 group production lots together into ’spirals’ or ’increments’. These groupings, as well as an increased...important reference point for this work. The analysis of the modification process presented in this reserach , however, does help shed light on the...planning efforts. Chapter 7- The Future of Aircraft Modifications "Strategy is the art of making use of time and space . I am less concerned about the

Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns

USDA-ARS?s Scientific Manuscript database

Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Mol...

A Field Study of Traditional and Nontraditional Children's Baseball.

ERIC Educational Resources Information Center

Martens, Rainer; And Others

1984-01-01

Younger children often have problems playing baseball using adult rules because pitchers lack ability to throw consistently and batters have trouble hitting erratically thrown balls. A modification of adult rules allowed the team coach to pitch to batters. More offensive and defensive activity occurred in the nontraditional games than in…

Genome-wide mapping of histone H3 lysine 4 trimethylation in Eucalyptus grandis developing xylem

Treesearch

Steven G Hussey; Eshchar Mizrachi; Andrew Groover; Dave K Berger; Alexander A Myburg

2015-01-01

Background: Histone modifications play an integral role in plant development, but have been poorly studied inwoody plants. Investigating chromatin organization in wood-forming tissue and its role in regulating gene expression allows us to understand the mechanisms underlying cellular differentiation during xylogenesis (wood...

Internet Gaming Addiction: A Systematic Review of Empirical Research

ERIC Educational Resources Information Center

Kuss, Daria Joanna; Griffiths, Mark D.

2012-01-01

The activity of play has been ever present in human history and the Internet has emerged as a playground increasingly populated by gamers. Research suggests that a minority of Internet game players experience symptoms traditionally associated with substance-related addictions, including mood modification, tolerance and salience. Because the…

Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou's general pseudo amino acid composition.

PubMed

Ju, Zhe; Wang, Shi-Yun

2018-04-22

As one of the most important and common protein post-translational modifications, citrullination plays a key role in regulating various biological processes and is associated with several human diseases. The accurate identification of citrullination sites is crucial for elucidating the underlying molecular mechanisms of citrullination and designing drugs for related human diseases. In this study, a novel bioinformatics tool named CKSAAP_CitrSite is developed for the prediction of citrullination sites. With the assistance of support vector machine algorithm, the highlight of CKSAAP_CitrSite is to adopt the composition of k-spaced amino acid pairs surrounding a query site as input. As illustrated by 10-fold cross-validation, CKSAAP_CitrSite achieves a satisfactory performance with a Sensitivity of 77.59%, a Specificity of 95.26%, an Accuracy of 89.37% and a Matthew's correlation coefficient of 0.7566, which is much better than those of the existing prediction method. Feature analysis shows that the N-terminal space containing pairs may play an important role in the prediction of citrullination sites, and the arginines close to N-terminus tend to be citrullinated. The conclusions derived from this study could offer useful information for elucidating the molecular mechanisms of citrullination and related experimental validations. A user-friendly web-server for CKSAAP_CitrSite is available at 123.206.31.171/CKSAAP_CitrSite/. Copyright © 2017. Published by Elsevier B.V.

Activities of red blood cell anti-oxidative enzymes (SOD, GPx) and total anti-oxidative capacity of serum (TAS) in men with coronary atherosclerosis and in healthy pilots.

PubMed

Zawadzka-Bartczak, Ewelina

2005-09-01

Reactive oxygen species (ROS) have been proposed to play important pathogenic roles, especially in harmful oxidative modifications of low-density cholesterol. Redox balance within the organism is largely determined by the activities of anti-oxidative enzymes of red blood cells and by the total anti-oxidative capacity of the serum (TAS). SOD and GPx activities and TAS in 13 men aged 42-65 years with coronary atherosclerosis (group I) were compared with those of both 15 clinically healthy pilots matched for age and lipid abnormalities (cholesterol and triglycerides) (group II) and 14 age-matched pilots without lipid abnormalities (group III). There were statistically significant differences in SOD and GPx activities and in TAS between the groups. 1. SOD and GPx activities and TAS were lower in men with advanced coronary atherosclerosis that in age-matched clinically healthy men with similar dyslipidemia and were even further decreased compared with clinically healthy men without dyslipidemia. 2. The decrease in SOD and GPx activities and TAS in men with advanced coronary atherosclerosis was more pronounced than the degree of hypercholesterolemia or hypertriglyceridemia. 3. If hyperlipidemia and the activity of antioxidative enzymes and TAS were considered without reference to other risk factors of atherosclerosis, it appeared that the decreases in SOD, GPx, and TAS may play a more important role in the development of the atherosclerotic process than isolated increases in free cholesterol or triglyceride levels.

A Proteomic Study of Brassinosteroid Response in Arabidopsis

PubMed Central

Deng, Zhiping; Zhang, Xin; Tang, Wenqiang; Oses-Prieto, Juan A; Suzuki, Nagi; Gendron, Joshua M; Chen, Huanjing; Guan, Shenheng; Chalkley, Robert J.; Peterman, T. Kaye; Burlingame, Alma L.; Wang, Zhi-Yong

2010-01-01

Summary The plant steroid hormones brassinosteroids (BRs) play an important role in a wide range of developmental and physiological processes. How BR signaling regulates diverse processes remains unclear. To understand the molecular details of BR responses, we have performed a proteomic study of BR-regulated proteins in Arabidopsis using two-dimensional difference gel electrophoresis (2-D DIGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 42 BR-regulated proteins, which are predicted to play potential roles in BR regulation of specific cellular processes, such as signaling, cytoskeleton rearrangement, vesicle trafficking, and biosynthesis of hormones and vitamins. Analyses of the BR insensitive mutant bri1-116 and BR hypersensitive mutant bzr1-1D identified 5 proteins (PATL1, PATL2, THI1, AtMDAR3 and NADP-ME2) affected by both BR-treatment and in the mutants, suggesting their importance in BR action. Selected proteins were further studied using insertion knockout mutants or immunoblotting. Interestingly, about 80% of the BR-responsive proteins were not identified in previous microarray studies, and direct comparison between protein- and RNA changes in BR mutants revealed a very weak correlation. RT-PCR analysis of selected genes revealed gene-specific kinetic relationships between RNA and protein responses. Furthermore, BR-regulated posttranslational modification of BiP2 protein was detected as spot shifts in 2-D DIGE. This study provides novel insights into the molecular networks that link BR signaling to specific cellular and physiological responses. PMID:17848588

Gyrofluid Modeling of Turbulent, Kinetic Physics

NASA Astrophysics Data System (ADS)

Despain, Kate Marie

2011-12-01

Gyrofluid models to describe plasma turbulence combine the advantages of fluid models, such as lower dimensionality and well-developed intuition, with those of gyrokinetics models, such as finite Larmor radius (FLR) effects. This allows gyrofluid models to be more tractable computationally while still capturing much of the physics related to the FLR of the particles. We present a gyrofluid model derived to capture the behavior of slow solar wind turbulence and describe the computer code developed to implement the model. In addition, we describe the modifications we made to a gyrofluid model and code that simulate plasma turbulence in tokamak geometries. Specifically, we describe a nonlinear phase mixing phenomenon, part of the E x B term, that was previously missing from the model. An inherently FLR effect, it plays an important role in predicting turbulent heat flux and diffusivity levels for the plasma. We demonstrate this importance by comparing results from the updated code to studies done previously by gyrofluid and gyrokinetic codes. We further explain what would be necessary to couple the updated gyrofluid code, gryffin, to a turbulent transport code, thus allowing gryffin to play a role in predicting profiles for fusion devices such as ITER and to explore novel fusion configurations. Such a coupling would require the use of Graphical Processing Units (GPUs) to make the modeling process fast enough to be viable. Consequently, we also describe our experience with GPU computing and demonstrate that we are poised to complete a gryffin port to this innovative architecture.

Functional analyses of cellulose synthase genes in flax (Linum usitatissimum) by virus-induced gene silencing.

PubMed

Chantreau, Maxime; Chabbert, Brigitte; Billiard, Sylvain; Hawkins, Simon; Neutelings, Godfrey

2015-12-01

Flax (Linum usitatissimum) bast fibres are located in the stem cortex where they play an important role in mechanical support. They contain high amounts of cellulose and so are used for linen textiles and in the composite industry. In this study, we screened the annotated flax genome and identified 14 distinct cellulose synthase (CESA) genes using orthologous sequences previously identified. Transcriptomics of 'primary cell wall' and 'secondary cell wall' flax CESA genes showed that some were preferentially expressed in different organs and stem tissues providing clues as to their biological role(s) in planta. The development for the first time in flax of a virus-induced gene silencing (VIGS) approach was used to functionally evaluate the biological role of different CESA genes in stem tissues. Quantification of transcript accumulation showed that in many cases, silencing not only affected targeted CESA clades, but also had an impact on other CESA genes. Whatever the targeted clade, inactivation by VIGS affected plant growth. In contrast, only clade 1- and clade 6-targeted plants showed modifications in outer-stem tissue organization and secondary cell wall formation. In these plants, bast fibre number and structure were severely impacted, suggesting that the targeted genes may play an important role in the establishment of the fibre cell wall. Our results provide new fundamental information about cellulose biosynthesis in flax that should facilitate future plant improvement/engineering. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine.

PubMed

Bukovsky, Antonin; Caudle, Michael R; Carson, Ray J; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M

2009-02-13

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders.

Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine

PubMed Central

Bukovsky, Antonin; Caudle, Michael R.; Carson, Ray J.; Gaytán, Francisco; Huleihel, Mahmoud; Kruse, Andrea; Schatten, Heide; Telleria, Carlos M.

2009-01-01

The immune system plays an important role in immunity (immune surveillance), but also in the regulation of tissue homeostasis (immune physiology). Lessons from the female reproductive tract indicate that immune system related cells, such as intraepithelial T cells and monocyte-derived cells (MDC) in stratified epithelium, interact amongst themselves and degenerate whereas epithelial cells proliferate and differentiate. In adult ovaries, MDC and T cells are present during oocyte renewal from ovarian stem cells. Activated MDC are also associated with follicular development and atresia, and corpus luteum differentiation. Corpus luteum demise resembles rejection of a graft since it is attended by a massive influx of MDC and T cells resulting in parenchymal and vascular regression. Vascular pericytes play important roles in immune physiology, and their activities (including secretion of the Thy-1 differentiation protein) can be regulated by vascular autonomic innervation. In tumors, MDC regulate proliferation of neoplastic cells and angiogenesis. Tumor infiltrating T cells die among malignant cells. Alterations of immune physiology can result in pathology, such as autoimmune, metabolic, and degenerative diseases, but also in infertility and intrauterine growth retardation, fetal morbidity and mortality. Animal experiments indicate that modification of tissue differentiation (retardation or acceleration) during immune adaptation can cause malfunction (persistent immaturity or premature aging) of such tissue during adulthood. Thus successful stem cell therapy will depend on immune physiology in targeted tissues. From this point of view, regenerative medicine is more likely to be successful in acute rather than chronic tissue disorders. PMID:20195382

Pre-fractionation strategies to resolve pea (Pisum sativum) sub-proteomes

PubMed Central

Meisrimler, Claudia-Nicole; Menckhoff, Ljiljana; Kukavica, Biljana M.; Lüthje, Sabine

2015-01-01

Legumes are important crop plants and pea (Pisum sativum L.) has been investigated as a model with respect to several physiological aspects. The sequencing of the pea genome has not been completed. Therefore, proteomic approaches are currently limited. Nevertheless, the increasing numbers of available EST-databases as well as the high homology of the pea and medicago genome (Medicago truncatula Gaertner) allow the successful identification of proteins. Due to the un-sequenced pea genome, pre-fractionation approaches have been used in pea proteomic surveys in the past. Aside from a number of selective proteome studies on crude extracts and the chloroplast, few studies have targeted other components such as the pea secretome, an important sub-proteome of interest due to its role in abiotic and biotic stress processes. The secretome itself can be further divided into different sub-proteomes (plasma membrane, apoplast, cell wall proteins). Cell fractionation in combination with different gel-electrophoresis, chromatography methods and protein identification by mass spectrometry are important partners to gain insight into pea sub-proteomes, post-translational modifications and protein functions. Overall, pea proteomics needs to link numerous existing physiological and biochemical data to gain further insight into adaptation processes, which play important roles in field applications. Future developments and directions in pea proteomics are discussed. PMID:26539198

A Broader View: Microbial Enzymes and Their Relevance in Industries, Medicine, and Beyond

PubMed Central

Bose, Sutapa; Rai, Vivek

2013-01-01

Enzymes are the large biomolecules that are required for the numerous chemical interconversions that sustain life. They accelerate all the metabolic processes in the body and carry out a specific task. Enzymes are highly efficient, which can increase reaction rates by 100 million to 10 billion times faster than any normal chemical reaction. Due to development in recombinant technology and protein engineering, enzymes have evolved as an important molecule that has been widely used in different industrial and therapeutical purposes. Microbial enzymes are currently acquiring much attention with rapid development of enzyme technology. Microbial enzymes are preferred due to their economic feasibility, high yields, consistency, ease of product modification and optimization, regular supply due to absence of seasonal fluctuations, rapid growth of microbes on inexpensive media, stability, and greater catalytic activity. Microbial enzymes play a major role in the diagnosis, treatment, biochemical investigation, and monitoring of various dreaded diseases. Amylase and lipase are two very important enzymes that have been vastly studied and have great importance in different industries and therapeutic industry. In this review, an approach has been made to highlight the importance of different enzymes with special emphasis on amylase and lipase in the different industrial and medical fields. PMID:24106701

Histone variant innovation in a rapidly evolving chordate lineage.

PubMed

Moosmann, Alexandra; Campsteijn, Coen; Jansen, Pascal Wtc; Nasrallah, Carole; Raasholm, Martina; Stunnenberg, Henk G; Thompson, Eric M

2011-07-15

Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture. We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs) and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome. These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.

O-GlcNAcylation: A New Cancer Hallmark?

PubMed

Fardini, Yann; Dehennaut, Vanessa; Lefebvre, Tony; Issad, Tarik

2013-01-01

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by O-GlcNAc-transferase (OGT) and removed by O-GlcNAcase, this dynamic modification is dependent on environmental glucose concentration. O-GlcNAcylation regulates the activities of a wide panel of proteins involved in almost all aspects of cell biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive nutritional intake, an important cancer risk factor, on protein activities and cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant role in cancer development through different mechanisms. O-GlcNAcylation and OGT levels are increased in different cancers (breast, prostate, colon…) and vary during cell cycle progression. Modulating their expression or activity can alter cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors have been shown to be directly O-GlcNAcylated (p53, MYC, NFκB, β-catenin…). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA methylation enzymes of the Tet family, involved epigenetic alterations associated with cancer, were recently found to interact with and target OGT to multi-molecular chromatin-remodeling complexes. Consistently, histones are subjected to O-GlcNAc modifications which regulate their function. Increasing number of evidences point out the central involvement of O-GlcNAcylation in tumorigenesis, justifying the attention received as a potential new approach for cancer treatment. However, comprehension of the underlying mechanism remains at its beginnings. Future challenge will be to address directly the role of O-GlcNAc-modified residues in oncogenic-related proteins to eventually propose novel strategies to alter cancer development and/or progression.

Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster

PubMed Central

Gerrits, Bertran; Roschitzki, Bernd; Mohanty, Sonali; Niederer, Eva M.; Laczko, Endre; Timmerman, Evy; Lange, Vinzenz; Hafen, Ernst; Aebersold, Ruedi; Vandekerckhove, Joël; Basler, Konrad; Ahrens, Christian H.; Gevaert, Kris; Brunner, Erich

2009-01-01

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X)PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X)PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species. PMID:19885390

ROSICS: CHEMISTRY AND PROTEOMICS OF CYSTEINE MODIFICATIONS IN REDOX BIOLOGY

PubMed Central

Kim, Hee-Jung; Ha, Sura; Lee, Hee Yoon; Lee, Kong-Joo

2015-01-01

Post-translational modifications (PTMs) occurring in proteins determine their functions and regulations. Proteomic tools are available to identify PTMs and have proved invaluable to expanding the inventory of these tools of nature that hold the keys to biological processes. Cysteine (Cys), the least abundant (1–2%) of amino acid residues, are unique in that they play key roles in maintaining stability of protein structure, participating in active sites of enzymes, regulating protein function and binding to metals, among others. Cys residues are major targets of reactive oxygen species (ROS), which are important mediators and modulators of various biological processes. It is therefore necessary to identify the Cys-containing ROS target proteins, as well as the sites and species of their PTMs. Cutting edge proteomic tools which have helped identify the PTMs at reactive Cys residues, have also revealed that Cys residues are modified in numerous ways. These modifications include formation of disulfide, thiosulfinate and thiosulfonate, oxidation to sulfenic, sulfinic, sulfonic acids and thiosulfonic acid, transformation to dehydroalanine (DHA) and serine, palmitoylation and farnesylation, formation of chemical adducts with glutathione, 4-hydroxynonenal and 15-deoxy PGJ2, and various other chemicals. We present here, a review of relevant ROS biology, possible chemical reactions of Cys residues and details of the proteomic strategies employed for rapid, efficient and sensitive identification of diverse and novel PTMs involving reactive Cys residues of redox-sensitive proteins. We propose a new name, “ROSics,” for the science which describes the principles of mode of action of ROS at molecular levels. © 2014 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Rapid Commun. Mass Spec Rev 34:184–208, 2015. PMID:24916017

Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.

PubMed

Gomes, A S; Alves, R N; Rønnestad, I; Power, D M

2015-09-01

Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified. Copyright © 2014 Elsevier Inc. All rights reserved.

SUMOylation of HSP27 by small ubiquitin-like modifier 2/3 promotes proliferation and invasion of hepatocellular carcinoma cells.

PubMed

Ge, Haize; Du, Juan; Xu, Jingman; Meng, Xiangliang; Tian, Jinchuan; Yang, Jie; Liang, Huimin

2017-08-03

Primary hepatocellular carcinoma (PHC) is a major health problem worldwide and is one of the 10 most commonly diagnosed cancers in China. Heat shock protein 27 (HSP27) were found to be overexpressed in a wide range of malignancies including PHC, however, post-translational modification of HSP27 still needs exploration in PHC. Recently, SUMOylation, an important post-translational modification associating with the development of many kinds of cancers has been intensively studied. In the current study, mRNA and protein level of HSP27 in archived tumor samples representing various pathological characteristics of PHC were examined, and modification of HSP27 by SUMO2/3 was investigated. HSP27 were expressed abundantly in patients' tumor tissues, and found to be associated with pathological progression. Besides, HSP27 was also elevated significantly in liver cancer cell lines Huh7 and HepG2 compared with human hepatocyte cells L02. Furthermore, knockdown of HSP27 was found to be associated with the decreased proliferation and invasion ability in Huh7 and HepG2 cells. Immunofluorescence assay showed that HSP27 and SUMO2/3 were co-localized in the subcellular, and co-immunoprecipitation verified the interaction between HSP27 and SUMO2/3. Overexpression of SUMO2/3 upregulated the HSP27 protein level and promotes Huh7 and HepG2 cell proliferation and invasion, and vice versa when the SUMO2/3 was knockdown. Taken together, increased protein level of HSP27 through SUMO2/3-mediated SUMOylation plays crucial roles in the progression of PHC, and this finding may shed light on developing potential therapeutic targets for PHC.

The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating

PubMed Central

Cui, Liying; Aleksandrov, Luba; Hou, Yue-Xian; Gentzsch, Martina; Chen, Jey-Hsin; Riordan, John R; Aleksandrov, Andrei A

2006-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel employing the ABC transporter structural motif. Deletion of a single residue (Phe508) in the first nucleotide-binding domain (NBD1), which occurs in most patients with cystic fibrosis, impairs both maturation and function of the protein. However, substitution of the Phe508 with small uncharged amino acids, including cysteine, is permissive for maturation. To explore the possible role of the phenylalanine aromatic side chain in channel gating we introduced a cysteine at this position in cysless CFTR, enabling its selective chemical modification by sulfhydryl reagents. Both cysless and wild-type CFTR ion channels have identical mean open times when activated by different nucleotide ligands. Moreover, both channels could be locked in an open state by introducing an ATPase inhibiting mutation (E1371S). However, the introduction of a single cysteine (F508C) prevented the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Chemical modification of cysless E1371S/F508C by sulfhydryl reagents was used to probe the role of the side chain in ion channel function. Specifically, benzyl-methanethiosulphonate modification of this variant restored the gating behaviour to that of cysless E1371S containing the wild-type phenylalanine at position 508. This provides the first direct evidence that a specific interaction of the Phe508 aromatic side chain plays a role in determining the residency time in the closed state. Thus, despite the fact that this aromatic side chain is not essential for CFTR folding, it is important in the ion channel function. PMID:16484308

O-GlcNAcylation: A New Cancer Hallmark?

PubMed Central

Fardini, Yann; Dehennaut, Vanessa; Lefebvre, Tony; Issad, Tarik

2013-01-01

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by O-GlcNAc-transferase (OGT) and removed by O-GlcNAcase, this dynamic modification is dependent on environmental glucose concentration. O-GlcNAcylation regulates the activities of a wide panel of proteins involved in almost all aspects of cell biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive nutritional intake, an important cancer risk factor, on protein activities and cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant role in cancer development through different mechanisms. O-GlcNAcylation and OGT levels are increased in different cancers (breast, prostate, colon…) and vary during cell cycle progression. Modulating their expression or activity can alter cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors have been shown to be directly O-GlcNAcylated (p53, MYC, NFκB, β-catenin…). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA methylation enzymes of the Tet family, involved epigenetic alterations associated with cancer, were recently found to interact with and target OGT to multi-molecular chromatin-remodeling complexes. Consistently, histones are subjected to O-GlcNAc modifications which regulate their function. Increasing number of evidences point out the central involvement of O-GlcNAcylation in tumorigenesis, justifying the attention received as a potential new approach for cancer treatment. However, comprehension of the underlying mechanism remains at its beginnings. Future challenge will be to address directly the role of O-GlcNAc-modified residues in oncogenic-related proteins to eventually propose novel strategies to alter cancer development and/or progression. PMID:23964270

A Halotyrosine Antibody that Detects Increased Protein Modifications in Asthma Patients

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

Jin, Hongjun; Hallstrand, Teal S.; Daly, Don S.

Background-Airway inflammation plays an important pathophysiological role in asthma. Eosinophils produce hypobromite and bromotyrosine while neutrophils produce hypochlorite and chlorotyrosine. Objective-To evaluate halotyrosine modifications of individual airway proteins as a marker of inflammation in asthma using an antibody-based assay. Methods-We developed a novel monoclonal antibody (BTK-94C) that binds halogenated tyrosine residues, and used this antibody in a custom enzyme-linked immunosorbent assay (ELISA) microarray platform to examine halotyrosine levels in 23 proteins in three independent sets of sputum samples (52 samples total). Results-In 15 subjects with either no asthma, or with asthma characterized by high or low sputum eosinophil counts, wemore » found associations between increased halotyrosine levels of at least three proteins and severity of airway hyperresponsiveness (AHR). Treatment with mepolizumab in 17 patients with sputum eosinophilia markedly reduced the sputum eosinophilia and significantly reduced halotyrosine levels in one sputum protein. Further analysis of 10 subjects with neutrophilic asthma and 10 health controls demonstrated a broad increase in halotyrosine in the patients with airway neutrophilia. Conclusions-Significantly higher levels of halotyrosine are associated with asthma in the asthma phenotypes we examined. The halotyrosine levels correlated with indirect AHR in the form of exercise-induced bronchoconstriction. Clinical Implication-An antibody-based assay for tyrosine halogenation in specific proteins may prove useful for assessing airway inflammation in asthma. Capsule Summary-An antibody to measure protein monobrominated tyrosine and other halotyrosine modifications was developed and used to evaluate halogenation in specific proteins in the airways for the first time. Associations were found between levels of halotyrosine and exercise-induced bronchoconstriction, and eosinophil and neutrophil inflammation in sputum from asthma patients. The ELISA developed here can be easily translated into a clinical test.« less

Psychiatric agriculture: systemic nutritional modification and mental health in the developing world.

PubMed

London, Douglas S; Stoll, Andrew L; Manning, Bruce B

2006-01-01

Modernization of agricultural systems to increase output causes changes to the nutritional content of food entire populations consume. Human nutritional needs differ from their "food", thus producing healthy agricultural products is not equivalent to providing agricultural products that are healthy for humans. Inclusion of the food production system as a factor in the increase of neuropsychiatric disorders and other chronic diseases helps explain negative trends in modern chronic diseases that remain unchecked despite stunning advances in modern medicine. Diseases in which our own technology plays a significant role include obesity and resulting disorders, such as diabetes, heart disease, hypertension, stroke and arthritis. Modernization's lure leads to importation of modern agricultural practices into a nutritionally vulnerable, malnourished and sometimes starving developing world. Wealthier nations hedge their food portfolio by having access to a wider variety of foods. The developing world's reliance on staple foods means even a minor widespread nutritional modification of one key food can have profound effects. New agricultural techniques may improve or exacerbate neuropsychiatric disorders through nutritional modification in regions where populations walk a nutritional tightrope with little margin for error. In most of the developing world western psychiatric interventions have failed to make inroads. People's consumption of fish has a demonstrated beneficial effect on their mental health and the omega-3 fatty acid content is a significant factor. Epidemiological, biological and agricultural studies implicate a lack of dietary omega-3s as a factor in certain mental disorders. Replenishing omega-3s has improved mental illnesses in controlled clinical trials. This article's detailed tilapia fish-farming model demonstrates how aquaculture/agriculture techniques can function as a public health intervention by increasing dietary omega-3s through creation of sustainable, economical and culturally appropriate food sources for the developing world.

Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines

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

Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun

Protein cysteine thiols play a crucial role in redox signaling, regulation of enzymatic activity and protein function, and maintaining redox homeostasis in living systems. The unique chemical reactivity of thiol groups makes cysteine susceptible to oxidative modifications by reactive oxygen and nitrogen species to form a broad array of reversible and irreversible protein post-translational modifications (PTMs). The reversible modifications in particular are one of the major components of redox signaling and are involved in regulation of various cellular processes under physiological and pathological conditions. The biological significance of these redox PTMs in health and diseases has been increasingly recognized. Herein,more » we review the recent advances of quantitative proteomic approaches for investigating redox PTMs in complex biological systems, including the general considerations of sample processing, various chemical or affinity enrichment strategies, and quantitative approaches. We also highlight a number of redox proteomic approaches that enable effective profiling of redox PTMs for addressing specific biological questions. Although some technological limitations remain, redox proteomics is paving the way towards a better understanding of redox signaling and regulation in human health and diseases.« less

New Insights Into Roles of Ubiquitin Modification in Regulating Plastids and Other Endosymbiotic Organelles.

PubMed

Broad, W; Ling, Q; Jarvis, P

2016-01-01

Recent findings have revealed important and diverse roles for the ubiquitin modification of proteins in the regulation of endosymbiotic organelles, which include the primary plastids of plants as well as complex plastids: the secondary endosymbiotic organelles of cryptophytes, alveolates, stramenopiles, and haptophytes. Ubiquitin modifications have a variety of potential consequences, both to the modified protein itself and to cellular regulation. The ubiquitin-proteasome system (UPS) can target individual proteins for selective degradation by the cytosolic 26S proteasome. Ubiquitin modifications can also signal the removal of whole endosymbiotic organelles, for example, via autophagy as has been well characterized in mitochondria. As plastids must import over 90% of their proteins from the cytosol, the observation that the UPS selectively targets the plastid protein import machinery is particularly significant. In this way, the UPS may influence the development and interconversions of different plastid types, as well as plastid responses to stress, by reconfiguring the organellar proteome. In complex plastids, the Symbiont-derived ERAD-Like Machinery (SELMA) has coopted the protein transport capabilities of the ER-Associated Degradation (ERAD) system, whereby misfolded proteins are retrotranslocated from ER for proteasomal degradation, uncoupling them from proteolysis: SELMA components have been retargeted to the second outermost plastid membrane to mediate protein import. In spite of this wealth of new information, there still remain a large number of unanswered questions and a need to define the roles of ubiquitin modification further in the regulation of plastids. Copyright © 2016 Elsevier Inc. All rights reserved.

Biochemical pharmacology of paradoxical sleep

PubMed Central

Gaillard, J. -M.

1983-01-01

1 The role of noradrenergic cells in the regulation of paradoxical sleep is still controversial, and experimental data have given rise to contradictory interpretations. 2 Early investigations focused primarily on chemical neurotransmissions. However, the process of information transmission between cells involves many other factors, and the cell surface is an important site for transduction of messages into modifications of the activity of postsynaptic cells. 3 α-adrenoceptors are believed to play an important role in the control of wakefulness and paradoxical sleep. Experimental evidence suggests that physiological modulation of receptor sensitivity, possibly by specific neuro-modulators, may be a key mechanism in synaptic transmission. 4 In the investigation of the mechanisms involved in paradoxical sleep regulation, lesions of the locus coeruleus have given equivocal results. Collateral inhibition, probably mediated by α2-adrenoceptors, appears to be a powerful mechanism. The exact temporal relationship between noradrenergic cell activation and paradoxical sleep production is not established, but 5-HT appears to be involved. Differences between paradoxical sleep and waking may be related to a physiological modulation of α2-adrenoceptor sensitivity. PMID:6140943

The Reaction between Nitric Oxide, Glutathione and Oxygen in the Presence and Absence of Protein: How are S-Nitrosothiols Formed?

PubMed Central

Keszler, Agnes; Zhang, Yanhong; Hogg, Neil

2009-01-01

The reaction between NO, thiols and oxygen has been studied in some detail in vitro due to its perceived importance in the mechanism of NO-dependent signal transduction. The formation of S-nitrosothiols and thiol disulfides from this chemistry has been suggested to be an important component of the biological chemistry of NO, and such subsequent thiol modifications may result in changes in cellular function and phenotype. In this study we have re-investigated this reaction using both experiment and simulation and conclude that: (i) S-Nitrosation through radical and non-radical pathways is occurring simultaneously (ii) S-Nitrosation through direct addition of NO to thiol does not occur to any meaningful extent and (iii) protein hydrophobic environments do not catalyze or enhance S-nitrosation of either themselves or of glutathione. We conclude that S-nitrosation and disulfide formation in this system occur only after the initial reaction between NO and oxygen to form nitrogen dioxide, and that hydrophobic protein environments are unlikely to play any role in enhancing and targeting S-nitrosothiol formation. PMID:19819329

Preparative two-step purification of recombinant H1.0 linker histone and its domains.

PubMed

Ivic, Nives; Bilokapic, Silvija; Halic, Mario

2017-01-01

H1 linker histones are small basic proteins that have a key role in the formation and maintenance of higher-order chromatin structures. Additionally, many examples have shown that linker histones play an important role in gene regulation, modulated by their various subtypes and posttranslational modifications. Obtaining high amounts of very pure linker histones, especially for efficient antibody production, remains a demanding and challenging procedure. Here we present an easy and fast method to purify human linker histone H1.0 overexpressed in Escherichia coli, as well as its domains: N-terminal/globular domain and C-terminal intrinsically disordered domain. This purification protocol relies on a simple affinity chromatography step followed by cation exchange due to the highly basic properties of histone proteins. Therefore, this protocol can also be applied to other linker histones. Highly pure proteins in amounts sufficient for most biochemical experiments can be obtained. The functional quality of purified H1.0 histone and its domains has been confirmed by pull-down, gel-mobility shift assays and the nuclear import assay.

Integration of immunological aspects in the European Human Embryonic Stem Cell Registry.

PubMed

Borstlap, Joeri; Kurtz, Andreas

2008-05-01

The immunological properties of stem cells are of increasing importance in regenerative medicine. Immunomodulatory mechanisms seem to play an important role not only with respect to the understanding of underlying mechanisms of autologous versus allogenic therapeutic approaches, but also for endogeneous tissue regeneration. The newly established European human embryonic stem cell registry (hESCreg) offers an international database for the registration, documentation and characterisation of human embryonic stem cells (hESC) and their use. By doing so, hESCreg aims to develop a model procedure for further standardisation efforts in the field of stem cell research and regenerative medicine, and eventually the registry may lead to a repository of therapy-related information. Currently the stem cell characterisation data acquired by the registry are divided into several categories such as cell derivation, culture conditions, genetic constitution, stem cell marker expression and degree of modification. This article describes immunological aspects of stem cell characterisation and explores the layout and relevance of a possible additional section to the hESCreg repository to include immunological characteristics of human embryonic stem cells.

Integrated Proteomics and Metabolomics Suggests Symbiotic Metabolism and Multimodal Regulation in a Fungal-Endobacterial System: Symbiotic Metabolism and Multimodal Regulation

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

Li, Zhou; Yao, Qiuming; Dearth, Stephen P.

Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes. While endobacteria play important roles in these tri-partite plant-fungal-endobacterial systems, the active physiology of fungal endobacteria has not been characterized extensively by systems biology approaches. Here in this paper, we use integrated proteomics and metabolomics to characterize the relationship between the endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata. In nitrogen-poor media, M. elongata had decreased growth but hosted a large and growing endobacterial population. The active endobacterium likely extracted malate from the fungal host as the primary carbon substrate for energy production and biosynthesis of phospho-sugars, nucleobases, peptidoglycan, andmore » some amino acids. The endobacterium obtained nitrogen by importing a variety of nitrogen-containing compounds. Further, nitrogen limitation significantly perturbed the carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated many pathways by concordant changes on enzyme abundances, post-translational modifications, reactant concentrations, and allosteric effectors. Lastly, such multimodal regulations may be a general mechanism for metabolic modulation.« less

Alternative Splicing in Neurogenesis and Brain Development.

PubMed

Su, Chun-Hao; D, Dhananjaya; Tarn, Woan-Yuh

2018-01-01

Alternative splicing of precursor mRNA is an important mechanism that increases transcriptomic and proteomic diversity and also post-transcriptionally regulates mRNA levels. Alternative splicing occurs at high frequency in brain tissues and contributes to every step of nervous system development, including cell-fate decisions, neuronal migration, axon guidance, and synaptogenesis. Genetic manipulation and RNA sequencing have provided insights into the molecular mechanisms underlying the effects of alternative splicing in stem cell self-renewal and neuronal fate specification. Timely expression and perhaps post-translational modification of neuron-specific splicing regulators play important roles in neuronal development. Alternative splicing of many key transcription regulators or epigenetic factors reprograms the transcriptome and hence contributes to stem cell fate determination. During neuronal differentiation, alternative splicing also modulates signaling activity, centriolar dynamics, and metabolic pathways. Moreover, alternative splicing impacts cortical lamination and neuronal development and function. In this review, we focus on recent progress toward understanding the contributions of alternative splicing to neurogenesis and brain development, which has shed light on how splicing defects may cause brain disorders and diseases.

In-circuit-measurement of parasitic elements in high gain high bandwidth low noise transimpedance amplifiers.

PubMed

Cochems, P; Kirk, A; Zimmermann, S

2014-12-01

Parasitic elements play an important role in the development of every high performance circuit. In the case of high gain, high bandwidth transimpedance amplifiers, the most important parasitic elements are parasitic capacitances at the input and in the feedback path, which significantly influence the stability, the frequency response, and the noise of the amplifier. As these parasitic capacitances range from a few picofarads down to only a few femtofarads, it is nearly impossible to measure them accurately using traditional LCR meters. Unfortunately, they also cannot be easily determined from the transfer function of the transimpedance amplifier, as it contains several overlapping effects and its measurement is only possible when the circuit is already stable. Therefore, we developed an in-circuit measurement method utilizing minimal modifications to the input stage in order to measure its parasitic capacitances directly and with unconditional stability. Furthermore, using the data acquired with this measurement technique, we both proposed a model for the complicated frequency response of high value thick film resistors as they are used in high gain transimpedance amplifiers and optimized our transimpedance amplifier design.