De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial.

Science.gov (United States)

Clark, Richard E; Polydoros, Fotios; Apperley, Jane F; Milojkovic, Dragana; Pocock, Christopher; Smith, Graeme; Byrne, Jenny L; de Lavallade, Hugues; O'Brien, Stephen G; Coffey, Tony; Foroni, Letizia; Copland, Mhairi

2017-07-01

Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia with deep molecular responses; however, patients with stable major molecular response (MMR), but not MR4, have not been studied, nor has the effect of treatment de-escalation rather than outright cessation. We aimed to examine the effects of treatment de-escalation as a prelude to complete cessation, not only in patients with MR4 or greater, but also in those with MMR but not MR4. We did this interim analysis of a non-randomised, phase 2 trial at 20 hospitals in the UK. We recruited patients (aged ≥18 years) with chronic myeloid leukaemia in first chronic phase who had received TKI for 3 years or more and were either in stable MR4 (BCR-ABL1:ABL1 ratio 0·1%) on two consecutive samples. The primary endpoint of this interim analysis was the proportion of patients who lost MMR on de-escalation and regained MMR on TKI resumption. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01804985. Between Dec 16, 2013 and April 10, 2015, we enrolled 174 patients into the MMR cohort (n=49) or the MR4 cohort (n=125). During the 12 months of half-dose therapy, 12 patients (7%) had molecular recurrence, all of whom regained MMR within 4 months of full-dose TKI resumption (median time to recovery 77 days). Recurrence was significantly lower in the MR4 cohort (three [2%; 90% CI 0·2-4·8] of 121 evaluable patients) than in the MMR cohort (nine [19%; 90% CI 9·5-28·0] of 48 evaluable patients; hazard ratio 0·12, 90% CI 0·04-0·37; p=0·0007), but was unrelated to previous TKI or TKI therapy duration. Adverse events (eg, lethargy, diarrhoea, rash, and nausea) improved during the first 3 months of de-escalation, though not thereafter. 16 serious adverse events were reported, including one fatality due to worsening pre-existing peripheral arterial occlusive disease in a patient who had received only imatinib. TKI de

Computation of Dielectric Response in Molecular Solids for High Capacitance Organic Dielectrics.

Science.gov (United States)

Heitzer, Henry M; Marks, Tobin J; Ratner, Mark A

2016-09-20

The dielectric response of a material is central to numerous processes spanning the fields of chemistry, materials science, biology, and physics. Despite this broad importance across these disciplines, describing the dielectric environment of a molecular system at the level of first-principles theory and computation remains a great challenge and is of importance to understand the behavior of existing systems as well as to guide the design and synthetic realization of new ones. Furthermore, with recent advances in molecular electronics, nanotechnology, and molecular biology, it has become necessary to predict the dielectric properties of molecular systems that are often difficult or impossible to measure experimentally. In these scenarios, it is would be highly desirable to be able to determine dielectric response through efficient, accurate, and chemically informative calculations. A good example of where theoretical modeling of dielectric response would be valuable is in the development of high-capacitance organic gate dielectrics for unconventional electronics such as those that could be fabricated by high-throughput printing techniques. Gate dielectrics are fundamental components of all transistor-based logic circuitry, and the combination high dielectric constant and nanoscopic thickness (i.e., high capacitance) is essential to achieving high switching speeds and low power consumption. Molecule-based dielectrics offer the promise of cheap, flexible, and mass producible electronics when used in conjunction with unconventional organic or inorganic semiconducting materials to fabricate organic field effect transistors (OFETs). The molecular dielectrics developed to date typically have limited dielectric response, which results in low capacitances, translating into poor performance of the resulting OFETs. Furthermore, the development of better performing dielectric materials has been hindered by the current highly empirical and labor-intensive pace of synthetic

Multi-objective evolutionary emergency response optimization for major accidents

International Nuclear Information System (INIS)

Georgiadou, Paraskevi S.; Papazoglou, Ioannis A.; Kiranoudis, Chris T.; Markatos, Nikolaos C.

2010-01-01

Emergency response planning in case of a major accident (hazardous material event, nuclear accident) is very important for the protection of the public and workers' safety and health. In this context, several protective actions can be performed, such as, evacuation of an area; protection of the population in buildings; and use of personal protective equipment. The best solution is not unique when multiple criteria are taken into consideration (e.g. health consequences, social disruption, economic cost). This paper presents a methodology for multi-objective optimization of emergency response planning in case of a major accident. The emergency policy with regards to protective actions to be implemented is optimized. An evolutionary algorithm has been used as the optimization tool. Case studies demonstrating the methodology and its application in emergency response decision-making in case of accidents related to hazardous materials installations are presented. However, the methodology with appropriate modification is suitable for supporting decisions in assessing emergency response procedures in other cases (nuclear accidents, transportation of hazardous materials) or for land-use planning issues.

The inflammatory cytokines: molecular biomarkers for major depressive disorder?

Science.gov (United States)

Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

2015-01-01

Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

Molecularly Imprinted Polymers with Stimuli-Responsive Affinity: Progress and Perspectives

OpenAIRE

Wei Chen; Yue Ma; Jianmin Pan; Zihui Meng; Guoqing Pan; Börje Sellergren

2015-01-01

Intelligent stimuli-responsive molecularly imprinted polymers (SR-MIPs) have attracted considerable research interest in recent years due to the potential applications in drug delivery, biotechnology and separation sciences. This review comprehensively summarizes various SR-MIPs, including the design and applications of thermo-responsive MIPs, pH-responsive MIPs, photo-responsive MIPs, biomolecule-responsive MIPs and ion-responsive MIPs. Besides the development of current SR-MIPs, the advanta...

Innate immune responses activated in Arabidopsis roots by microbe-associated molecular patterns.

Science.gov (United States)

Millet, Yves A; Danna, Cristian H; Clay, Nicole K; Songnuan, Wisuwat; Simon, Matthew D; Werck-Reichhart, Danièle; Ausubel, Frederick M

2010-03-01

Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of beta-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid-jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways.

Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion

DEFF Research Database (Denmark)

Santoni-Rugiu, Eric; Jelnes, Peter; Thorgeirsson, Snorri S

2005-01-01

created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations...... cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment...

Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.

Directory of Open Access Journals (Sweden)

Yongsheng Huang

2011-08-01

Full Text Available Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza.

Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

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Michelle A Favila

2015-12-01

Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei; Welch, Megan J.; Ryu, Tae Woo; Zhang, Huoming; Berumen, Michael L.; Nilsson, Gö ran E.; Munday, Philip L.; Ravasi, Timothy

2016-01-01

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Molecular signatures of transgenerational response to ocean acidification in a species of reef fish

KAUST Repository

Schunter, Celia Marei

2016-07-29

The impact of ocean acidification on marine ecosystems will depend on species capacity to adapt. Recent studies show that the behaviour of reef fishes is impaired at projected CO levels; however, individual variation exists that might promote adaptation. Here, we show a clear signature of parental sensitivity to high CO in the brain molecular phenotype of juvenile spiny damselfish, Acanthochromis polyacanthus, primarily driven by circadian rhythm genes. Offspring of CO -tolerant and CO -sensitive parents were reared at near-future CO (754 μatm) or present-day control levels (414 μatm). By integrating 33 brain transcriptomes and proteomes with a de novo assembled genome we investigate the molecular responses of the fish brain to increased CO and the expression of parental tolerance to high CO in the offspring molecular phenotype. Exposure to high CO resulted in differential regulation of 173 and 62 genes and 109 and 68 proteins in the tolerant and sensitive groups, respectively. Importantly, the majority of differences between offspring of tolerant and sensitive parents occurred in high CO conditions. This transgenerational molecular signature suggests that individual variation in CO sensitivity could facilitate adaptation of fish populations to ocean acidification.

Prediction of electroconvulsive therapy response and remission in major depression : meta-analysis

OpenAIRE

Diermen, van, Linda; Ameele, van den, Seline; Kamperman, Astrid M.; Sabbe, Bernard G.C.; Vermeulen, Tom; Schrijvers, Didier; Birkenhager, Tom K.

2018-01-01

Abstract: Background Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. Method A meta-analysis was conducted according to t...

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Science.gov (United States)

Pamenter, Matthew E.; Powell, Frank L.

2016-01-01

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

Molecular mechanisms of radioadaptive responses in human lymphoblastoid cells

International Nuclear Information System (INIS)

Kakimoto, Ayana; Taki, Keiko; Nakajima, Tetsuo

2008-01-01

Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored the molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-amino-benzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation even in the presence of 3AB. These findings suggested that molecular mechanisms of the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration, although we could not exclude a possibility that the differential effects of 3AB was due to cell type difference. Finally, by performing a comprehensive analysis of alterations in gene expression using high coverage expression profiling (HiCEP), we could identify 17 genes whose expressions were significantly altered 6 h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expressions of which were different with or without priming

Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.

Science.gov (United States)

Gat-Viks, Irit; Chevrier, Nicolas; Wilentzik, Roni; Eisenhaure, Thomas; Raychowdhury, Raktima; Steuerman, Yael; Shalek, Alex K; Hacohen, Nir; Amit, Ido; Regev, Aviv

2013-04-01

Individual genetic variation affects gene responsiveness to stimuli, often by influencing complex molecular circuits. Here we combine genomic and intermediate-scale transcriptional profiling with computational methods to identify variants that affect the responsiveness of genes to stimuli (responsiveness quantitative trait loci or reQTLs) and to position these variants in molecular circuit diagrams. We apply this approach to study variation in transcriptional responsiveness to pathogen components in dendritic cells from recombinant inbred mouse strains. We identify reQTLs that correlate with particular stimuli and position them in known pathways. For example, in response to a virus-like stimulus, a trans-acting variant responds as an activator of the antiviral response; using RNA interference, we identify Rgs16 as the likely causal gene. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in circuits that control responses to stimuli.

Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

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Jahnavi Aluri

2018-02-01

Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

Radio-adaptation: cellular and molecular features of a response to low levels of ionizing radiation

International Nuclear Information System (INIS)

Rigaud, O.

1998-01-01

It is well established that sublethal doses of DNA damaging agents induce protective mechanisms against a subsequent high dose treatment ; for instance, the phenomenon of radio-adaptation in the case of ionizing radiations. Since the early observation described in 1984, numerous studies have confirmed the radio-adaptive response in terms of reduction of chromosomal breaks for varied biological models in vitro and in vivo. Evidence for an adaptive response against the induction of gene mutations and the lethal effect is clearly demonstrated. This paper reviews the experimental results describing various aspects of these adaptive responses expressed on these different biological end-points. The molecular mechanism underlying radio-adaptation still remains nuclear. The development of this phenomenon requires de novo synthesis of transcripts and proteins during the time interval between the two doses. Some data are consistent with the hypotheses that these gene products would be involved in the activation of DNA repair pathways and antioxidant systems. However, a major question still remains unanswered; indeed, it is not clear whether or not the radio-adaptation could affect the estimation of cancer risk related with low level exposure to ionizing radiation, a major concern in radioprotection. Until such data are available, it is yet unwise to evoke the beneficial effects of radio-adaptation. (authors)

Physiological response, molecular analysis and water use efficiency ...

African Journals Online (AJOL)

With a view to study the effects of irrigation scheduling on the water use efficiency and physiological response and molecular basis of maize hybrids of different maturity groups, a field experiment was conducted at Water Management Research Center (WMRC), Belvatagi, University of Agricultural Sciences, Dharwad, India ...

Skin: Major target organ of allergic reactions to small molecular weight compounds

International Nuclear Information System (INIS)

Merk, Hans F.; Baron, Jens M.; Neis, Mark M.; Obrigkeit, Daniela Hoeller; Karlberg, Ann-Therese

2007-01-01

Skin is a major target organ for allergic reactions to small molecular weight compounds. Drug allergic reactions may be life-threatening such as in the case of anaphylactic reactions or bullous drug reactions and occur in about 5% of all hospitalized patients. Allergic contact dermatitis has an enormous influence on the social life of the patient because it is the most frequent reason for occupational skin diseases and the treatment and prevention of this disease cost approximately Euro 3 billion per year in Germany. The different proposed pathophysiological pathways leading to a drug eruption are discussed in this paper. All major enzymes which are involved in the metabolism of xenobiotica were shown to be present in skin. Evidence supporting the role of metabolism in the development of drug allergy and allergic contact dermatitis is demonstrated in the example of sulphonamides and fragrances

Molecular Cloning, Characterization, and Expression of Cuc m 2, a Major Allergen in Cucumis melo

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Mojtaba Sankian

2013-05-01

Full Text Available Background: Several studies reported the clinical features of IgE-mediated hypersensitivity after ingestion of melon. Melon allergy is a common IgE-mediated fruit allergy in Iran. This prompted us to investigate immunochemical and molecular properties of the major allergen in melon fruit, to compare the IgE-binding capacity of the natural protein with the recombinant allergen, and to determine cross-reactivity of the major allergen with closely-related allergens from other plants displaying clinical cross-reactivity with melon. Methods: Identification and molecular characterization of the major melon allergen were performed using IgE immunoblotting, allergen-specific ELISA, affinity-based purifications, cross-inhibition assays, cloning, and expression of the allergen in Escherichia coli. Results: Melon profilin was identified and isolated as a major IgE-binding component and designated as Cuc m 2. Sequencing corresponding cDNA revealed an open reading frame of 363 bp coding for 131 amino acid residues and two fragments of 171 bp and 383 bps for the 5’and 3’ UTRs, respectively. Significant cross-reactivity was found between melon profilin and Cynodon dactylon, tomato, peach, and grape profilins in cross-inhibition assays. Although the highest degree of amino acid identity was revealed with watermelon profilin, there was no significant cross-reactivity between melon and watermelon profilins. Conclusion: Melon profilin is the major IgE-binding component in melon extract, and the recombinant and natural forms exhibited similar IgE-binding capacities. A part of the fruit-fruit and pollen-fruit cross-reactions could be explained by the presence of this conserved protein; however, sequence homology provides insufficient information to predict IgE cross-reactivity of profilins.

Molecular Responses to the Zika Virus in Mosquitoes

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Catalina Alfonso-Parra

2018-05-01

Full Text Available The Zika virus (ZIKV, originally discovered in 1947, did not become a major concern until the virus swept across the Pacific and into the Americas in the last decade, bringing with it news of neurological complications and birth defects in ZIKV affected areas. This prompted researchers to dissect the molecular interactions between ZIKV and the mosquito vector in an attempt to better understand not only the changes that occur upon infection, but to also identify molecules that may potentially enhance or suppress a mosquito’s ability to become infected and/or transmit the virus. Here, we review what is currently known regarding ZIKV-mosquito molecular interactions, focusing on ZIKV infection of Aedes aegypti and Aedes albopictus, the primary species implicated in transmitting ZIKV during the recent outbreaks.

Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

Science.gov (United States)

Kudoh, Hiroshi

2016-04-01

Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

The developments and applications of molecular nuclear medicine

International Nuclear Information System (INIS)

Fang Shengwei; Xi Wang; Zhang Hong

2009-01-01

Molecular nuclear medicine including PET and SPECT is one of the most important parts of the molecular imaging. The combinations of molecular unclear medicine with CT, MRI, ultrasound or optical imaging and synthesis of multimodality radiopharmaceuticals are the major trends of the development of nuclear medicine. Molecular nuclear medicine has more and more and more important value on the monitoring of response to biology involved gene therapy or stem cell therapy and the developments of new drug. (authors)

Facts and Fiction: The Impact of Hypothermia on Molecular Mechanisms following Major Challenge

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Michael Frink

2012-01-01

Full Text Available Numerous multiple trauma and surgical patients suffer from accidental hypothermia. While induced hypothermia is commonly used in elective cardiac surgery due to its protective effects, accidental hypothermia is associated with increased posttraumatic complications and even mortality in severely injured patients. This paper focuses on protective molecular mechanisms of hypothermia on apoptosis and the posttraumatic immune response. Although information regarding severe trauma is limited, there is evidence that induced hypothermia may have beneficial effects on the posttraumatic immune response as well as apoptosis in animal studies and certain clinical situations. However, more profound knowledge of mechanisms is necessary before randomized clinical trials in trauma patients can be initiated.

Molecular responses and expression analysis of genes in a ...

African Journals Online (AJOL)

Haloxylon ammodendron (C.A Mey.) Bunge is a xero-halophytic desert shrub with excellent drought resistance and salt tolerance. To decipher the molecular responses involved in its drought resistance, the cDNA-AFLP (amplified fragment length polymorphism) technique was employed to identify genes expressed ...

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus.

Science.gov (United States)

O'Hanlon, Karen A; Margison, Geoffrey P; Hatch, Amy; Fitzpatrick, David A; Owens, Rebecca A; Doyle, Sean; Jones, Gary W

2012-09-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O(6)-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O(6)-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system.

Molecular characterization of an adaptive response to alkylating agents in the opportunistic pathogen Aspergillus fumigatus

Science.gov (United States)

O’Hanlon, Karen A.; Margison, Geoffrey P.; Hatch, Amy; Fitzpatrick, David A.; Owens, Rebecca A.; Doyle, Sean; Jones, Gary W.

2012-01-01

An adaptive response to alkylating agents based upon the conformational change of a methylphosphotriester (MPT) DNA repair protein to a transcriptional activator has been demonstrated in a number of bacterial species, but this mechanism appears largely absent from eukaryotes. Here, we demonstrate that the human pathogen Aspergillus fumigatus elicits an adaptive response to sub-lethal doses of the mono-functional alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We have identified genes that encode MPT and O6-alkylguanine DNA alkyltransferase (AGT) DNA repair proteins; deletions of either of these genes abolish the adaptive response and sensitize the organism to MNNG. In vitro DNA repair assays confirm the ability of MPT and AGT to repair methylphosphotriester and O6-methylguanine lesions respectively. In eukaryotes, the MPT protein is confined to a select group of fungal species, some of which are major mammalian and plant pathogens. The evolutionary origin of the adaptive response is bacterial and rooted within the Firmicutes phylum. Inter-kingdom horizontal gene transfer between Firmicutes and Ascomycete ancestors introduced the adaptive response into the Fungal kingdom. Our data constitute the first detailed characterization of the molecular mechanism of the adaptive response in a lower eukaryote and has applications for development of novel fungal therapeutics targeting this DNA repair system. PMID:22669901

Prediction of electroconvulsive therapy response and remission in major depression: Meta-analysis

NARCIS (Netherlands)

Van Diermen, L. (Linda); Van Den Ameele, S. (Seline); A.M. Kamperman (Astrid); Sabbe, B.C.G. (Bernard C.G.); Vermeulen, T. (Tom); Schrijvers, D. (Didier); T.K. Birkenhäger (Tom)

2018-01-01

textabstractElectroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

Science.gov (United States)

Chung, Pil Seung; Song, Wonyup; Biegler, Lorenz T.; Jhon, Myung S.

2017-05-01

During the operation of hard disk drive (HDD), the perfluoropolyether (PFPE) lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″) by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

Directory of Open Access Journals (Sweden)

Pil Seung Chung

2017-05-01

Full Text Available During the operation of hard disk drive (HDD, the perfluoropolyether (PFPE lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic and loss (viscous moduli (G′ and G″ by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Plant genetic and molecular responses to water deficit

Directory of Open Access Journals (Sweden)

Silvio Salvi

2011-02-01

Full Text Available Plant productivity is severely affected by unfavourable environmental conditions (biotic and abiotic stresses. Among others, water deficit is the plant stress condition which mostly limits the quality and the quantity of plant products. Tolerance to water deficit is a polygenic trait strictly dependent on the coordinated expression of a large set of genes coding for proteins directly involved in stress-induced protection/repair mechanisms (dehydrins, chaperonins, enzymes for the synthesis of osmoprotectants and detoxifying compounds, and others as well as genes involved in transducing the stress signal and regulating gene expression (transcription factors, kinases, phosphatases. Recently, research activities in the field evolved from the study of single genes directly involved in cellular stress tolerance (functional genes to the identification and characterization of key regulatory genes involved in stress perception and transduction and able to rapidly and efficiently activate the complex gene network involved in the response to stress. The complexity of the events occurring in response to stress have been recently approached by genomics tools; in fact the analysis of transcriptome, proteome and metabolome of a plant tissue/cell in response to stress already allowed to have a global view of the cellular and molecular events occurring in response to water deficit, by the identification of genes activated and co-regulated by the stress conditions and the characterization of new signalling pathways. Moreover the recent application of forward and reverse genetic approaches, trough mutant collection development, screening and characterization, is giving a tremendous impulse to the identification of gene functions with key role in stress tolerance. The integration of data obtained by high-throughput genomic approaches, by means of powerful informatic tools, is allowing nowadays to rapidly identify of major genes/QTLs involved in stress tolerance

Transparency of Reporting in Molecular Diagnostics

Directory of Open Access Journals (Sweden)

Stephen Bustin

2013-07-01

Full Text Available The major advances made over the past few years in molecular and cell biology are providing a progressively more detailed understanding of the molecular pathways that control normal processes and become dysregulated in disease [1]. This has resulted in the documentation of numerous genetic, epigenetic, transcriptomic, proteomic and metabolomic biomarkers that promise earlier disease detection, more accurate patient stratification and better prognosis [2–5]. Furthermore, molecular fingerprinting of diseases can be predictive of drug response and so assist with specific targeting of drugs against disease-associated molecules and function [6]. [...

Innate Immune Responses Activated in Arabidopsis Roots by Microbe-Associated Molecular Patterns[W][OA

Science.gov (United States)

Millet, Yves A.; Danna, Cristian H.; Clay, Nicole K.; Songnuan, Wisuwat; Simon, Matthew D.; Werck-Reichhart, Danièle; Ausubel, Frederick M.

2010-01-01

Despite the fact that roots are the organs most subject to microbial interactions, very little is known about the response of roots to microbe-associated molecular patterns (MAMPs). By monitoring transcriptional activation of β-glucuronidase reporters and MAMP-elicited callose deposition, we show that three MAMPs, the flagellar peptide Flg22, peptidoglycan, and chitin, trigger a strong tissue-specific response in Arabidopsis thaliana roots, either at the elongation zone for Flg22 and peptidoglycan or in the mature parts of the roots for chitin. Ethylene signaling, the 4-methoxy-indole-3-ylmethylglucosinolate biosynthetic pathway, and the PEN2 myrosinase, but not salicylic acid or jasmonic acid signaling, play major roles in this MAMP response. We also show that Flg22 induces the cytochrome P450 CYP71A12-dependent exudation of the phytoalexin camalexin by Arabidopsis roots. The phytotoxin coronatine, an Ile-jasmonic acid mimic produced by Pseudomonas syringae pathovars, suppresses MAMP-activated responses in the roots. This suppression requires the E3 ubiquitin ligase COI1 as well as the transcription factor JIN1/MYC2 but does not rely on salicylic acid–jasmonic acid antagonism. These experiments demonstrate the presence of highly orchestrated and tissue-specific MAMP responses in roots and potential pathogen-encoded mechanisms to block these MAMP-elicited signaling pathways. PMID:20348432

RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus

Science.gov (United States)

2011-01-01

Background In a context of climate change, phenotypic plasticity provides long-lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. Results Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by-treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. Conclusions For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance

Molecular responses and expression analysis of genes in a ...

African Journals Online (AJOL)

STORAGESEVER

2009-06-17

Jun 17, 2009 ... Molecular responses and expression analysis of genes in a xerophytic desert shrub Haloxylon ammodendron .... physiological determination and cDNA-AFLP analysis, three groups of seeds were sowed in pots with sand and .... HaDR27. U. 234. PDR-like ABC transporter. AT1G59870. HaDR28. U. 135.

Dating the Time of Origin of Major Clades: Molecular Clocks and the Fossil Record

Science.gov (United States)

Smith, Andrew B.; Peterson, Kevin J.

Molecular and paleontological data provide independent means of estimating when groups of organisms evolved in the geological past, but neither approach can be considered straightforward. The single most fundamental obstacle to developing an accurate estimate of times of origination from gene sequence data is variation in rates of molecular evolution, both through time and among lineages. Although various techniques have been proposed to circumvent this problem, none unambiguously allow the components of time and rate to be separated. Furthermore, problems of establishing accurate calibration points, correctly rooted phylogenies, and accurate estimates of branch length remain formidable. Conversely, paleontological dates fix only the latest possible time of divergence, and so probabilistic methods are required to set a lower boundary on origination dates. Realistic confidence intervals that take preservational biases into account are only just becoming available. Although molecular and paleontological approaches to dating often agree reasonably well, there are two notable areas of disagreement; when mammal and bird orders originated and when the major phyla originated. The discrepancy in dating bird/mammal ordinal origins probably reflects a global rock-record bias. Paleontological sampling in the Late Cretaceous is still too restricted geographically to draw any firm conclusions about the existence of a pre-Tertiary record for modern orders of bird or mammal from anywhere other than North America. Dating the time of origin of phyla is more complicated, and is confounded by both preservational biases and problems of molecular clock estimation.

Molecular and physiological responses of trees to waterlogging stress.

Science.gov (United States)

Kreuzwieser, Jürgen; Rennenberg, Heinz

2014-10-01

One major effect of global climate change will be altered precipitation patterns in many regions of the world. This will cause a higher probability of long-term waterlogging in winter/spring and flash floods in summer because of extreme rainfall events. Particularly, trees not adapted at their natural site to such waterlogging stress can be impaired. Despite the enormous economic, ecological and social importance of forest ecosystems, the effect of waterlogging on trees is far less understood than the effect on many crops or the model plant Arabidopsis. There is only a handful of studies available investigating the transcriptome and metabolome of waterlogged trees. Main physiological responses of trees to waterlogging include the stimulation of fermentative pathways and an accelerated glycolytic flux. Many energy-consuming, anabolic processes are slowed down to overcome the energy crisis mediated by waterlogging. A crucial feature of waterlogging tolerance is the steady supply of glycolysis with carbohydrates, particularly in the roots; stress-sensitive trees fail to maintain sufficient carbohydrate availability resulting in the dieback of the stressed tissues. The present review summarizes physiological and molecular features of waterlogging tolerance of trees; the focus is on carbon metabolism in both, leaves and roots of trees. © 2014 John Wiley & Sons Ltd.

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

Directory of Open Access Journals (Sweden)

Zhao Y

2015-06-01

Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

Federal Radiological Monitoring and Assessment Center (FRMAC), US response to major radiological accidents

International Nuclear Information System (INIS)

Mueller, P.G.

2000-01-01

During the 1960's and 70's the expanded use of nuclear materials to generate electricity, to provide medical benefits, and for research purposes continued to grow in the United States. While substantial effort went into constructing plants and facilities and providing for a number of redundant backup systems for safety purposes, little effort went into the development of emergency response plans for possible major radiological accidents. Unfortunately, adequate plans and procedures had not been developed to co-ordinate either state or federal emergency response assets and personnel should a major radiological accident occur. This situation became quite evident following the Three Mile Island Nuclear Reactor accident in 1979. An accident of that magnitude had not been adequately prepared for and Pennsylvania's limited emergency radiological resources and capabilities were quickly exhausted. Several federal agencies with statutory responsibilities for emergency response, including the U.S. Environmental Protection Agency (EPA), U.S. Department of Energy (DOE), Federal Emergency Management Agency (FEMA), Nuclear Regulatory Commission (NRC), and others provided extensive assistance and support during the accident. However, the assistance was not fully co-ordinated nor controlled. Following the Three Mile Island incident 13 federal agencies worked co-operatively to develop an agreement called the Federal Radiological Emergency Response Plan (FRERP). Signed in November 1985, this plan delineated the statutory responsibilities and authorities of each federal agency signatory to the FRERP. In the event of a major radiological accident, the FRERP would be activated to ensure that a co-ordinated federal emergency response would be available to respond to any major radiological accident scenario. The FRERP encompasses a wide variety of radiological accidents, not just those stemming from nuclear power plants. Activation of the FRERP could occur from major accidents involving

Anchoring novel molecular biomarker responses to traditional responses in fish exposed to environmental contamination

International Nuclear Information System (INIS)

Nogueira, Patricia; Pacheco, Mario; Lourdes Pereira, M.; Mendo, Sonia; Rotchell, Jeanette M.

2010-01-01

The responses of Dicentrarchus labrax and Liza aurata to aquatic pollution were assessed in a contaminated coastal lagoon, using both traditional and novel biomarkers combined. DNA damage, assessed by comet assay, was higher in both fish species from the contaminated sites, whereas levels of cytochrome P450 1A1 gene expression were not significantly altered. The liver histopathological analysis also revealed significant lesions in fish from contaminated sites. Alterations in ras and xpf genes were analysed and additional pollutant-responsive genes were identified. While no alterations were found in ras gene, a downregulation of xpf gene was observed in D. labrax from a contaminated site. Suppression subtractive hybridization applied to D. labrax collected at a contaminated site, revealed altered expression in genes involved in energy metabolism, immune system activity and antioxidant response. The approach and results reported herein demonstrate the utility of anchoring traditional biomarker responses alongside novel biomarker responses. - Novel molecular biomarkers of aquatic environmental contamination in fish.

Planned Pregnancy in a Chronic Myeloid Leukemia Patient in Molecular Remission

Science.gov (United States)

Pavlovsky, Carolina; Giere, Isabel; Van Thillo, Germán

2012-01-01

Excellent response rates and a good quality of life have been observed since the introduction of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) treatment. Consequently, some challenges began to appear in CML women in child-bearing age wishing to become pregnant. Currently, many women around the world are in stable major/complete molecular response MMR/CMR (MMR: <0.1% BCR-ABL/ABL and CMR: undetectable BCR-ABL mRNA by RQ-PCR transcript levels on the international scale). The condition of stable MMR/CMR is linked to a long-term virtual absence of progression to the accelerated and blastic phase and to the possibility of stopping the TKI treatment with the maintenance of a condition of CMR in a proportion of cases. Imatinib teratogenic and prescribing information prohibits the use of it during pregnancy. We describe the case of a 36-year-old female patient with CML in chronic phase who stopped imatinib after 2 years in major molecular response (MMR) to plan a pregnancy. Molecular monitoring by RQ-PCR was performed quarterly. She achieved a safe pregnancy and delivery maintaining an optimal molecular response throughout the pregnancy. Isolated literature reports have been described, but no formal advice has been described at present time. PMID:22928126

Abiotic stressors and stress responses

DEFF Research Database (Denmark)

Sulmon, Cecile; Van Baaren, Joan; Cabello-Hurtado, Francisco

2015-01-01

Abstract Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we...... review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact...... life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental...

Stress responses during ageing: molecular pathways regulating protein homeostasis.

Science.gov (United States)

Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

2015-01-01

The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

Molecular and physiological responses to abiotic stress in forest trees and their relevance to tree improvement.

Science.gov (United States)

Harfouche, Antoine; Meilan, Richard; Altman, Arie

2014-11-01

Abiotic stresses, such as drought, salinity and cold, are the major environmental stresses that adversely affect tree growth and, thus, forest productivity, and play a major role in determining the geographic distribution of tree species. Tree responses and tolerance to abiotic stress are complex biological processes that are best analyzed at a systems level using genetic, genomic, metabolomic and phenomic approaches. This will expedite the dissection of stress-sensing and signaling networks to further support efficient genetic improvement programs. Enormous genetic diversity for stress tolerance exists within some forest-tree species, and due to advances in sequencing technologies the molecular genetic basis for this diversity has been rapidly unfolding in recent years. In addition, the use of emerging phenotyping technologies extends the suite of traits that can be measured and will provide us with a better understanding of stress tolerance. The elucidation of abiotic stress-tolerance mechanisms will allow for effective pyramiding of multiple tolerances in a single tree through genetic engineering. Here we review recent progress in the dissection of the molecular basis of abiotic stress tolerance in forest trees, with special emphasis on Populus, Pinus, Picea, Eucalyptus and Quercus spp. We also outline practices that will enable the deployment of trees engineered for abiotic stress tolerance to land owners. Finally, recommendations for future work are discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Prediction of the molecular response to pertubations from single cell measurements].

Science.gov (United States)

Remacle, Françoise; Levine, Raphael D

2014-12-01

The response of protein signalization networks to perturbations is analysed from single cell measurements. This experimental approach allows characterizing the fluctuations in protein expression levels from cell to cell. The analysis is based on an information theoretic approach grounded in thermodynamics leading to a quantitative version of Le Chatelier principle which allows to predict the molecular response. Two systems are investigated: human macrophages subjected to lipopolysaccharide challenge, analogous to the immune response against Gram-negative bacteria and the response of the proteins involved in the mTOR signalizing network of GBM cancer cells to changes in partial oxygen pressure. © 2014 médecine/sciences – Inserm.

National response plan - Major nuclear or radiological accidents

International Nuclear Information System (INIS)

2014-02-01

France has been implementing stringent radiation protection and nuclear safety and security measures for many years. However, this does not mean that the country is exempt from having to be prepared to deal with an emergency. Changes in France, Europe and other parts of the globe have made it necessary for France to reconsider how it responds to nuclear and radiological emergencies. As the potential impact of a nuclear or radiological accident can affect a wide range of activities, the plan described herein is based on a cross-sector and inter-ministerial approach to emergency response. The Chernobyl and Fukushima-Daiichi disasters are proof that the consequences of a major nuclear or radiological accident can affect all levels of society. These challenges are substantial and relate to: public health: An uncontrolled nuclear accident can have immediate consequences (death, injury, irradiation) as well as long-term consequences that can lead to increased risk of developing radiation-induced diseases (such as certain types of cancer); environmental quality: Radiation contamination can last for several decades and, in some cases, can result in an area being closed off permanently to the public; economic and social continuity: Nuclear accidents bring human activity to a halt in contaminated areas, disrupting the economic and social order of the entire country. It may therefore be necessary to adapt economic and social systems and carry out clean-up operations if people and businesses have been displaced; quality of international relations: Related to fulfillment of obligations to alert and inform European and international partners. This international dimension also covers the protection of French nationals present in countries stricken by a nuclear accident. This national plan provides reference information on how to prepare for a nuclear or radiological emergency and make the appropriate decisions in the event of an emergency. It covers the emergency phase (including

Molecular cloning and characterization of an α-amylase cDNA highly expressed in major feeding stages of the coffee berry borer, Hypothenemus hampei.

Science.gov (United States)

Bezerra, C A; Macedo, L L P; Amorim, T M L; Santos, V O; Fragoso, R R; Lucena, W A; Meneguim, A M; Valencia-Jimenez, A; Engler, G; Silva, M C M; Albuquerque, E V S; Grossi-de-Sa, M F

2014-12-10

α-Amylases are common enzymes responsible for hydrolyzing starch. Insect-pests, whose larvae develop in seeds, rely obligatorily on α-amylase activity to digest starch, as their major food source. Considering the relevance of insect α-amylases and the natural α-amylase inhibitors present in seeds to protect from insect damage, we report here the molecular cloning and nucleotide sequence of the full-length AmyHha cDNA of the coffee berry borer, Hypothenemus hampei, a major insect-pest of coffee crops. The AmyHha sequence has 1879 bp, containing a 1458 bp open reading frame, which encodes a predicted protein with 485 amino acid residues, with a predicted molecular mass of 51.2 kDa. The deduced protein showed 55-79% identity to other insect α-amylases, including Anthonomus grandis, Ips typographus and Sitophilus oryzae α-amylases. In depth analysis revealed that the highly conserved three amino acid residues (Asp184, Glu220, and Asp285), which compose the catalytic site are also presented in AmyHha amylase. The AmyHha gene seems to be a single copy in the haploid genome and AmyHha transcription levels were found higher in L2 larvae and adult insects, both corresponding to major feeding phases. Modeling of the AmyHha predicted protein uncovered striking structural similarities to the Tenebrio molitor α-amylase also displaying the same amino acid residues involved in enzyme catalysis (Asp184, Glu220 and Asp285). Since AmyHha gene was mostly transcribed in the intestinal tract of H. hampei larvae, the cognate α-amylase could be considered a high valuable target to coffee bean insect control by biotechnological strategies. Copyright © 2014. Published by Elsevier B.V.

Growth response of microorganisms to different molecular fractions of lignite

Energy Technology Data Exchange (ETDEWEB)

Polman, J.K.; Breckenridge, C.R.; Dugan, P.R.; Quigley, D.R.

1990-01-01

Our research is primarily concerned with isolating and characterizing microbes which are able to dissimilate coal and convert it to other useful chemicals. This quarter, general growth responses of microorganisms cultivated in the presence of different molecular weight fractions of lignite coal were examined. Aerobic and anaerobic environmental samples from a variety of ecological niches were used as inocula. Growth of the microorganisms in these samples on the following types of media was tested: COAL medium, containing alkali-solubilized whole coal; THFI medium, containing the alkali-solubilized, tetrahydrofuran-insoluble, macromolecular portion of whole coal; THFS medium, containing the THF-soluble, low molecular weight portion of whole coal; and CON medium, void of any coal constituent. Overall results indicated that the presence of the THF-soluble, low molecular weight coal fraction enhanced the growth yield and the variety of aerobic microorganisms compared to the other coal fractions or the control medium. Conversely, anaerobic microbes grew best on media which contained the macromolecular fraction. 12 refs., 5 tabs.

Molecular, physiological and behavioral responses of honey bee (Apis mellifera) drones to infection with microsporidian parasites.

Science.gov (United States)

Holt, Holly L; Villar, Gabriel; Cheng, Weiyi; Song, Jun; Grozinger, Christina M

2018-04-26

Susceptibility to pathogens and parasites often varies between sexes due to differences in life history traits and selective pressures. Nosema apis and Nosema ceranae are damaging intestinal pathogens of European honey bees (Apis mellifera). Nosema pathology has primarily been characterized in female workers where infection is energetically costly and accelerates worker behavioral maturation. Few studies, however, have examined infection costs in male honey bees (drones) to determine if Nosema similarly affects male energetic status and sexual maturation. We infected newly emerged adult drones with Nosema spores and conducted a series of molecular, physiological, and behavioral assays to characterize Nosema etiology in drones. We found that infected drones starved faster than controls and exhibited altered patterns of flight activity in the field, consistent with energetic distress or altered rates of sexual maturation. Moreover, expression of candidate genes with metabolic and/or hormonal functions, including members of the insulin signaling pathway, differed by infection status. Of note, while drone molecular responses generally tracked predictions based on worker studies, several aspects of infected drone flight behavior contrasted with previous observations of infected workers. While Nosema infection clearly imposed energetic costs in males, infection had no impact on drone sperm numbers and had only limited effects on antennal responsiveness to a major queen sex pheromone component (9-ODA). We compare Nosema pathology in drones with previous studies describing symptoms in workers and discuss ramifications for drone and colony fitness. Copyright © 2018. Published by Elsevier Inc.

Who is responsible for the team’s results? Media framing of sports actors’ responsibility in major sports competitions

Directory of Open Access Journals (Sweden)

Diana Luiza Dumitriu

2016-05-01

Full Text Available Media are no longer just a witness to sports events, facilitating our access to them, but have become the most powerful judging platform for sports competitions, serving as a guide for their interpretation and evaluation. The present study focuses on media framing of sports actors’ responsibility when it comes to major sports competitions. Who is responsible for the team’s performance and results? In analysing media discourse, framing effects of sports events coverage will be examined from two inter-correlated dimensions, textually and visually. Based on an event-related corpus of on-line press articles from four national newspapers, this case study covers two major sports events: 2010 European Women’s Handball Championship and 2011 World Women’s Handball Championship. The discursive analysis of the press articles shows that, if winning competitive settings favour the emergence of a personification effect, building up sports heroes on both textual and visual dimensions, the responsibility of failure is rather diffused towards a collective referent. However, the visual component of press articles, along with the indirect strategy of addressing the responsibility issue throughout reported speech techniques, works as an alternative to the personification effect.

Lengthening our perspective: morphological, cellular, and molecular responses to eccentric exercise.

Science.gov (United States)

Hyldahl, Robert D; Hubal, Monica J

2014-02-01

The response of skeletal muscle to unaccustomed eccentric exercise has been studied widely, yet it is incompletely understood. This review is intended to provide an up-to-date overview of our understanding of how skeletal muscle responds to eccentric actions, with particular emphasis on the underlying molecular and cellular mechanisms of damage and recovery. This review begins by addressing the question of whether eccentric actions result in physical damage to muscle fibers and/or connective tissue. We next review the symptomatic manifestations of eccentric exercise (i.e., indirect damage markers, such as delayed onset muscle soreness), with emphasis on their relatively poorly understood molecular underpinnings. We then highlight factors that potentially modify the muscle damage response following eccentric exercise. Finally, we explore the utility of using eccentric training to improve muscle function in populations of healthy and aging individuals, as well as those living with neuromuscular disorders. Copyright © 2013 Wiley Periodicals, Inc.

Molecular markers predicting radiotherapy response: Report and recommendations from an International Atomic Energy Agency technical meeting

International Nuclear Information System (INIS)

West, Catharine M.L.; McKay, Michael J.; Hoelscher, Tobias; Baumann, Michael; Stratford, Ian J.; Bristow, Robert G.; Iwakawa, Mayumi; Imai, Takashi; Zingde, Surekha M.; Anscher, Mitchell S.; Bourhis, Jean; Begg, Adrian C.; Haustermans, Karin; Bentzen, Soren M.; Hendry, Jolyon H.

2005-01-01

Purpose: There is increasing interest in radiogenomics and the characterization of molecular profiles that predict normal tissue and tumor radioresponse. A meeting in Amsterdam was organized by the International Atomic Energy Agency to discuss this topic on an international basis. Methods and Materials: This report is not completely exhaustive, but highlights some of the ongoing studies and new initiatives being carried out worldwide in the banking of tumor and normal tissue samples underpinning the development of molecular marker profiles for predicting patient response to radiotherapy. It is generally considered that these profiles will more accurately define individual or group radiosensitivities compared with the nondefinitive findings from the previous era of cellular-based techniques. However, so far there are only a few robust reports of molecular markers predicting normal tissue or tumor response. Results: Many centers in different countries have initiated tissue and tumor banks to store samples from clinical trials for future molecular profiling analysis, to identify profiles that predict for radiotherapy response. The European Society for Therapeutic Radiology and Oncology GENEtic pathways for the Prediction of the effects of Irradiation (GENEPI) project, to store, document, and analyze sample characteristics vs. response, is the most comprehensive in this regard. Conclusions: The next 5-10 years are likely to see the results of these and other correlative studies, and promising associations of profiles with response should be validated in larger definitive trials

Molecular MR imaging

International Nuclear Information System (INIS)

Fleige, G.; Hamm, B.

2000-01-01

Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.) [de

Molecular radio-oncology

International Nuclear Information System (INIS)

Baumann, Michael; Krause, Mechthild; Cordes, Nils

2016-01-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Molecular radio-oncology

Energy Technology Data Exchange (ETDEWEB)

Baumann, Michael; Krause, Mechthild; Cordes, Nils (eds.) [Technische Univ. Dresden (Germany). Faculty of Medicine and University Hospital

2016-07-01

This book concisely reviews our current understanding of hypoxia, molecular targeting, DNA repair, cancer stem cells, and tumor pathophysiology, while also discussing novel strategies for putting these findings into practice in daily clinical routine. Radiotherapy is an important part of modern multimodal cancer treatment, and the past several years have witnessed not only substantial improvements in radiation techniques and the use of new beam qualities, but also major strides in our understanding of molecular tumor biology and tumor radiation response. Against this backdrop, the book highlights recent efforts to identify reasonable and clinically applicable biomarkers using broad-spectrum tissue microarrays and high-throughput systems biology approaches like genomics and epigenomics. In particular, it describes in detail how such molecular information is now being exploited for diagnostic imaging and imaging throughout treatment using the example of positron emission tomography. By discussing all these issues in the context of modern radiation oncology, the book provides a broad, up-to-date overview of the molecular aspects of radiation oncology that will hopefully foster its further optimization.

Turning randomness into meaning at the molecular level using Muller's morphs.

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Henson, Kathleen; Cooper, Melanie M; Klymkowsky, Michael W

2012-04-15

While evolutionary theory follows from observable facts and logical inferences (Mayr, 1985), historically, the origin of novel inheritable variations was a major obstacle to acceptance of natural selection (Bowler, 1992; Bowler, 2005). While molecular mechanisms address this issue (Jablonka and Lamb, 2005), analysis of responses to the Biological Concept Inventory (BCI) (Klymkowsky et al., 2010), revealed that molecular biology majors rarely use molecular level ideas in their discourse, implying that they do not have an accessible framework within which to place evolutionary variation. We developed a "Socratic tutorial" focused on Muller's categorization of mutations' phenotypic effects (Muller, 1932). Using a novel vector-based method to analyzed students' essay responses, we found that a single interaction with this tutorial led to significant changes in thinking toward a clearer articulation of the effects of mutational change. We suggest that Muller's morphs provides an effective framework for facilitating student learning about mutational effects and evolutionary mechanisms.

Turning randomness into meaning at the molecular level using Muller's morphs

Directory of Open Access Journals (Sweden)

Kathleen Henson

2012-02-01

While evolutionary theory follows from observable facts and logical inferences (Mayr, 1985, historically, the origin of novel inheritable variations was a major obstacle to acceptance of natural selection (Bowler, 1992; Bowler, 2005. While molecular mechanisms address this issue (Jablonka and Lamb, 2005, analysis of responses to the Biological Concept Inventory (BCI (Klymkowsky et al., 2010, revealed that molecular biology majors rarely use molecular level ideas in their discourse, implying that they do not have an accessible framework within which to place evolutionary variation. We developed a “Socratic tutorial” focused on Muller's categorization of mutations' phenotypic effects (Muller, 1932. Using a novel vector-based method to analyzed students' essay responses, we found that a single interaction with this tutorial led to significant changes in thinking toward a clearer articulation of the effects of mutational change. We suggest that Muller's morphs provides an effective framework for facilitating student learning about mutational effects and evolutionary mechanisms.

Molecular imaging in cervical cancer

International Nuclear Information System (INIS)

KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

2016-01-01

Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

Molecular mechanisms of plant response to ionising radiation. Exploration of the glucosinolate role in the anti-oxidative response

International Nuclear Information System (INIS)

Gicquel, M.

2012-01-01

Terrestrial organisms are exposed to low doses of ionising radiation from natural or anthropogenic sources. The major effects of the radiations are due to DNA deterioration and water radiolysis which generates an oxidative stress by free radical production. Plants constitute good models to study the effects of ionising radiations and the search of antioxidant molecules because of their important secondary metabolism. Thus this thesis, funded by the Brittany region, characterized the physiological and molecular response of the model plant Arabidopsis thaliana to low (10 Gy) and moderate (40 Gy) doses of ionising radiation, and was therefore interested in glucosinolates, characteristic compounds of the Brassicaceae family. The global proteomic and transcriptomic studies carried out on this model revealed (1) a common response for both doses dealing with the activation of DNA repair mechanisms, cell cycle regulation and protection of cellular structures; (2) an adjustment of the energetic metabolism and an activation of secondary compounds biosynthesis (i.e. glucosinolates and flavonoids) after the 10 Gy dose; (3) an induction of enzymatic control of ROS, the regulation of cellular components recycling and of programmed cell death after the 40 Gy dose. The potential anti-oxidative role of glucosinolates was then explored. The in vitro anti-oxidative power of some glucosinolates and their derivative products were demonstrated. Their modulating effects against irradiation-induced damages were then tested in vivo by simple experimental approaches. The importance of the glucosinolate level to give a positive or negative effect was demonstrated. (author)

UV radiation in marine ectotherms: Molecular effects and responses

International Nuclear Information System (INIS)

Dahms, Hans-U.; Lee, Jae-Seong

2010-01-01

This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

Mesocosm Community Response Sensitivities to Specific Conductivity Comprised of Different Major Ions

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Traditional toxicity test assays have been used to evaluate the relative sensitivity to different major ion mixtures as a proxy for understanding what the response of aquatic species growing in their natural environment would be during exposure to specific conductivity stress ema...

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

International Nuclear Information System (INIS)

Ng, Loo-Teck; Nakayama, Hiroshi; Kaetsu, Isao; Uchida, Kumao

2005-01-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs

Photocuring of stimulus responsive membranes for controlled-release of drugs having different molecular weights

Energy Technology Data Exchange (ETDEWEB)

Ng, Loo-Teck [School of Science, Food and Horticulture, University of Western Sydney, Locked bag 1797, Penrith South DC, NSW 1797 (Australia)]. E-mail: l.ng@uws.edu.au; Nakayama, Hiroshi [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan); Kaetsu, Isao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)]. E-mail: kaetsu@ned.kindai.ac.jp; Uchida, Kumao [Department of Nuclear Engineering, Faculty of Science and technology, Kinki University, Kowakae, 3-4-1, Higashi-Osaka 577-8502 (Japan)

2005-06-01

Intelligent drug delivery membranes were prepared by photocuring poly(acrylic acid) coatings onto poly(2-hydroxyethyl methacrylate) membranes each with model drugs of different molecular weights being incorporated. pH-responsive release behaviours of the model drugs which included sodium salicylate, nicotinamide, nicotinic acid, methylene blue, brilliant green and crystal violet were investigated. Only the membrane with methylene blue incorporated showed a clear pH-responsive release and other drug-incorporated membranes showed no intelligent behaviour. These phenomena were explained in terms of the difference in diffusivity of drugs through polymer matrices of the membranes attributable to the difference in the molecular weights of drugs.

Estimation of brain activation in response to major and minor scales by fMRI

International Nuclear Information System (INIS)

Fujimaki, Takuya; Nemoto, Iku

2011-01-01

We made fMRI measurements of the brain responses to major and minor scales which are the fundamental elements for making melodies in music. In addition, we used an arpeggio of diminished 7th. For a control stimulus, we provided a sequence of repeated single tones. The ascending scales of 12 major and 12 minor keys were made starting from F no.3 to F4. Each scale was 3 s in duration. A 3 s scan was performed 2-3 s (randomized) after a scale has been finished and repeated every 14 s (sparse time scanning). Typically, major scales activated the left inferior frontal gyrus, minor scales the posterior cingulate gyrus and the diminished arpeggio the left auditory cortex. In general, the left hemisphere was more activated than usually seen in responses to music. (author)

Molecular cloning, expression and characterization of Pru a 1, the major cherry allergen.

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Scheurer, S; Metzner, K; Haustein, D; Vieths, S

1997-06-01

A high percentage of birch pollen allergic patients experiences food hypersensitivity reactions after ingestion of several fruits and vegetables. Previous work demonstrated common epitopes on an allergen of Mr 18,000 from sweet cherry (Prunus avium) and Bet v 1, the major allergen from birch pollen. N-terminal amino acid sequencing showed a sequence identity of 67% with Bet v 1. Here we report the cloning and cDNA sequencing of this cherry allergen. The entire deduced amino acid sequence described a protein of Mr 17,700 with 59.1% identity to Bet v 1. High degrees of identity in the range of 40 to 60% were also found with related allergens from other kinds of tree pollen and plant foods as well as with stress-induced proteins from food plants such as parsley, potato and soya. The coding DNA of the cherry protein was cloned into vector pET-16b and expressed in E. coli strain BL21(DE3) as a His-tag fusion protein. As shown by SDS-PAGE, the apparent molecular masses of the nonfusion protein and the natural allergen were identical. The fusion protein showed high IgE binding potency when sera from patients allergic to cherry were tested by immunoblotting and enzyme allergosorbent tests. Moreover, it cross-reacted strongly with IgE specific for the natural counterpart and for Bet v 1. The high biological activity of the recombinant fusion protein was further confirmed by the induction of a strong histamine release in basophils from cherry-allergic patients. Since sera from 17/19 of such patients contained IgE against this allergen it was classified as a major allergen and named Pru a 1. Recombinant Pru a 1 mimics most of the allergenic potency of cherry extract and hence could be a useful tool for studying the molecular and immunological properties of pollen related food allergens.

Techniques for Maximizing the Performance of Molecular Pathology Testing: Responsibilities of All Pathologists

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Evren UZUN

2018-05-01

Full Text Available Molecular pathological analysis has an expanding role in patient diagnosis and management. The performance of these techniques relies on excellent laboratory procedures. However, the crucial step is obtaining the best samples for molecular analysis. Archiving and selection of these are the responsibilities of all pathologists even if they are not working at a center with molecular pathological facilities. This review focuses on the features of different types of materials for molecular pathological analysis. Many steps that might affect the results, including communication between the pathologist and the oncology team, features of different types of materials (cytological, tissue blocks, biopsy, circulating tumor cells (CTCs and cell-free circulating nucleic acids, effects of tissue processing, methods for selecting the best material, and tissue saving and tumor enrichment methods are discussed. The procedures for referral to a center for molecular pathological analysis are also mentioned. Awareness of the importance of the cytopathological and histopathological material of the patients for future molecular pathological analysis by pathologists is of the utmost importance.

Glucose-responsive insulin by molecular and physical design

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Bakh, Naveed A.; Cortinas, Abel B.; Weiss, Michael A.; Langer, Robert S.; Anderson, Daniel G.; Gu, Zhen; Dutta, Sanjoy; Strano, Michael S.

2017-10-01

The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker. The aim of this Perspective is to highlight emerging concepts, including mathematical modelling and the molecular engineering of insulin itself and its potency, towards a viable GRI. We briefly outline some of the most important recent progress toward this goal and also provide a forward-looking viewpoint, which asks if there are new approaches that could spur innovation in this area as well as to encourage synthetic chemists and chemical engineers to address the challenges and promises offered by this therapeutic approach.

The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold and heat

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Kazuo eNakashima

2014-05-01

Full Text Available Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs are master regulators of gene expression. ABRE-binding protein (AREB and ABRE-binding factor (ABF TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein (DREB TFs and NAC TFs are also involved in stress responses including drought, heat and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these transcription factors in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

The transcriptional regulatory network in the drought response and its crosstalk in abiotic stress responses including drought, cold, and heat.

Science.gov (United States)

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2014-01-01

Drought negatively impacts plant growth and the productivity of crops around the world. Understanding the molecular mechanisms in the drought response is important for improvement of drought tolerance using molecular techniques. In plants, abscisic acid (ABA) is accumulated under osmotic stress conditions caused by drought, and has a key role in stress responses and tolerance. Comprehensive molecular analyses have shown that ABA regulates the expression of many genes under osmotic stress conditions, and the ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. Transcription factors (TFs) are master regulators of gene expression. ABRE-binding protein and ABRE-binding factor TFs control gene expression in an ABA-dependent manner. SNF1-related protein kinases 2, group A 2C-type protein phosphatases, and ABA receptors were shown to control the ABA signaling pathway. ABA-independent signaling pathways such as dehydration-responsive element-binding protein TFs and NAC TFs are also involved in stress responses including drought, heat, and cold. Recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress responses. The important roles of these TFs in crosstalk among abiotic stress responses will be discussed. Control of ABA or stress signaling factor expression can improve tolerance to environmental stresses. Recent studies using crops have shown that stress-specific overexpression of TFs improves drought tolerance and grain yield compared with controls in the field.

Deep molecular responses for treatment-free remission in chronic myeloid leukemia.

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Dulucq, Stéphanie; Mahon, Francois-Xavier

2016-09-01

Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

An overview of HCV molecular biology, replication and immune responses

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Nawaz Zafar

2011-04-01

Full Text Available Abstract Hepatitis C virus (HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. In this review, we summarize molecular virology, replication and immune responses against HCV and discussed how HCV escape from adaptive and humoral immune responses. This advance knowledge will be helpful for development of vaccine against HCV and discovery of new medicines both from synthetic chemistry and natural sources.

Indigoid Photoswitches: Visible Light Responsive Molecular Tools.

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Petermayer, Christian; Dube, Henry

2018-05-15

Indigoid photoswitches comprise a class of chromophores that are derived from the parent and well-known indigo dye. Different from most photoswitches their core structures absorb in the visible region of the spectrum in both isomeric states even without substitutions, which makes them especially interesting for applications not tolerant of high-energy UV light. Also different from most current photoswitching systems, they provide highly rigid structures that undergo large yet precisely controllable geometry changes upon photoisomerization. The favorable combination of pronounced photochromism, fast and efficient photoreactions, and high thermal bistability have led to a strongly increased interest in indigoid photoswitches over the last years. As a result, intriguing applications of these chromophores as reversible triggering units in supramolecular and biological chemistry, the field of molecular machines, or smart molecules have been put forward. In this Account current developments in the synthesis, mechanistic understanding of light responsiveness, advantageous properties as phototools, and new applications of indigoid photoswitches are summarized with the focus on hemithioindigo, hemiindigo, and indigo as key examples. Many methods for the synthesis of hemithioindigos are known, but derivatives with a fourth substituent at the double bond could not easily be prepared because of the resulting increased steric hindrance in the products. Recent efforts in our laboratory have provided two different methods to prepare these highly promising photoswitches in very efficient ways. One method is especially designed for the introduction of sterically hindered ketones while the second one allows rapid structural diversification in only three high-yielding synthetic steps. Given the lesser prominence of indigoid photoswitches, mechanistic understanding of their excited state behavior and therefore rational design opportunities for photophysical properties are also much

Professionally responsible intrapartum management of patients with major mental disorders.

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Babbitt, Kriste E; Bailey, Kala J; Coverdale, John H; Chervenak, Frank A; McCullough, Laurence B

2014-01-01

Pregnant women with major mental disorders present obstetricians with a range of clinical challenges, which are magnified when a psychotic or agitated patient presents in labor and there is limited time for decision making. This article provides the obstetrician with an algorithm to guide professionally responsible decision making with these patients. We searched for articles related to the intrapartum management of pregnant patients with major mental disorders, using 3 main search components: pregnancy, chronic mental illness, and ethics. No articles were found that addressed the clinical ethical challenges of decision making during the intrapartum period with these patients. We therefore developed an ethical framework with 4 components: the concept of the fetus as a patient; the presumption of decision-making capacity; the concept of assent; and beneficence-based clinical judgment. On the basis of this framework we propose an algorithm to guide professionally responsible decision making that asks 5 questions: (1) Does the patient have the capacity to consent to treatment?; (2) Is there time to attempt restoration of capacity?; (3) Is there an opportunity for substituted judgment?; (4) Is the patient accepting treatment?; (5) Is there an opportunity for active assent?; and (6) coerced clinical management as the least worst alternative. The algorithm is designed to support a deliberative, clinically comprehensive, preventive-ethics approach to guide obstetricians in decision making with this challenging population of patients. Copyright © 2014 Mosby, Inc. All rights reserved.

[Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review].

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Romeo, B; Choucha, W; Fossati, P; Rotge, J-Y

2017-08-01

The aim of this review was to determine the clinical and biological predictors of the ketamine response. A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in

Molecular detection of Leishmania infection due to Leishmania major and Leishmania turanica in the vectors and reservoir host in Iran.

Science.gov (United States)

Rassi, Yavar; Oshaghi, Mohammad Ali; Azani, Sadegh Mohammadi; Abaie, Mohammad Reza; Rafizadeh, Sina; Mohebai, Mehdi; Mohtarami, Fatemeh; Zeinali, Mohammad kazem

2011-02-01

An epidemiological study was carried out on the vectors and reservoirs of cutaneous leishmaniasis in rural areas of Damghan district, Semnan province, central Iran, during 2008-2009. Totally, 6110 sand flies were collected using sticky papers and were subjected to molecular methods for detection of Leishmania parasite. Phlebotomus papatasi Scopoli was the common species in outdoor and indoor resting places. Polymerase chain reaction technique showed that 24 out of 218 P. papatasi (11%) and 4 out of 62 Phlebotomus caucasicus Marzinovskyi (6.5%) were positive for parasites Leishmania major Yakimoff and Schokhor. Twenty-one rodent reservoir hosts captured using Sherman traps were identified as Rhombomys opimus Lichtenstein (95%) and Meriones libycus Lichtenstein (5%). Microscopic investigation on blood smear of the animals for amastigote parasites revealed 8 (40%) rodents infected with R. opimus. L. major infection in these animals was then confirmed by polymerase chain reaction against internal transcribed spacer ribosomal DNA (rDNA) loci of the parasite followed by restriction fragment length polymorphism. Further, sequence analysis of 297 bp of ITS1-rDNA loci revealed the presence of L. major and Leishmania turanica in P. papatasi, and L. major in R. opimus. This is the first molecular report of L. major infection in both vectors (P. papatasi and P. caucasicus) and reservoir host (R. opimus) in this region. The results indicated that P. papatas was the primary vector of the disease and circulating the parasite between human and reservoirs, and P. caucasicus could be considered as a secondary vector. Further, our study showed that R. opimus is the most important host reservoir for maintenance of the parasite source in the area.

Medulloblastoma: Molecular Genetics and Animal Models

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Corey Raffel

2004-07-01

Full Text Available Medulloblastoma is a primary brain tumor found in the cerebellum of children. The tumor occurs in association with two inherited cancer syndromes: Turcot syndrome and Gorlin syndrome. Insights into the molecular biology of the tumor have come from looking at alterations in the genes altered in these syndromes, PTC and APC, respectively. Murine models of medulloblastoma have been constructed based on these alterations. Additional murine models that, while mimicking the appearance of the human tumor, seem unrelated to the human tumor's molecular alterations have been made. In this review, the clinical picture, origin, molecular biology, murine models of medulloblastoma are discussed. Although a great deal has been discovered about this tumor, the genetic alterations responsible for tumor development in a majority of patients have yet to be described.

New Insight in Understanding the mechanical responses of polymer glasses using molecular dynamic simulation

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Zheng, Yexin; Wang, Shi-Qing; Tsige, Mesfin

The Kremer-Grest bead-spring model has been the standard model in molecular dynamics simulation of polymer glasses. However, due to current computational limitations in accessing relevant time scales in polymer glasses in a reasonable amount of CPU time, simulation of mechanical response of polymer glasses in molecular dynamic simulations requires a much higher quenching rate and deformation rate than used in experiments. Despite several orders of magnitude difference in time scale between simulation and experiment, previous studies have shown that simulations can produce meaningful results that can be directly compared with experimental results. In this work we show that by tuning the quenching rate and deformation rate relative to the segmental relaxation times, a reasonable mechanical response shows up in the glassy state. Specifically, we show a younger glass prepared with a faster quenching rate shows glassy responses only when the imposed deformation rate is proportionally higher. the National Science Foundation (DMR-1444859 and DMR-1609977).

QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT

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Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all four components, but the greatest overall current...

Molecular evolution of the major chemosensory gene families in insects.

Science.gov (United States)

Sánchez-Gracia, A; Vieira, F G; Rozas, J

2009-09-01

Chemoreception is a crucial biological process that is essential for the survival of animals. In insects, olfaction allows the organism to recognise volatile cues that allow the detection of food, predators and mates, whereas the sense of taste commonly allows the discrimination of soluble stimulants that elicit feeding behaviours and can also initiate innate sexual and reproductive responses. The most important proteins involved in the recognition of chemical cues comprise moderately sized multigene families. These families include odorant-binding proteins (OBPs) and chemosensory proteins (CSPs), which are involved in peripheral olfactory processing, and the chemoreceptor superfamily formed by the olfactory receptor (OR) and gustatory receptor (GR) families. Here, we review some recent evolutionary genomic studies of chemosensory gene families using the data from fully sequenced insect genomes, especially from the 12 newly available Drosophila genomes. Overall, the results clearly support the birth-and-death model as the major mechanism of evolution in these gene families. Namely, new members arise by tandem gene duplication, progressively diverge in sequence and function, and can eventually be lost from the genome by a deletion or pseudogenisation event. Adaptive changes fostered by environmental shifts are also observed in the evolution of chemosensory families in insects and likely involve reproductive, ecological or behavioural traits. Consequently, the current size of these gene families is mainly a result of random gene gain and loss events. This dynamic process may represent a major source of genetic variation, providing opportunities for FUTURE specific adaptations.

Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

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Nicola Gaetano Gatta

2016-11-01

Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

Molecular dynamics simulation of potentiometric sensor response: the effect of biomolecules, surface morphology and surface charge.

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Lowe, B M; Skylaris, C-K; Green, N G; Shibuta, Y; Sakata, T

2018-05-10

The silica-water interface is critical to many modern technologies in chemical engineering and biosensing. One technology used commonly in biosensors, the potentiometric sensor, operates by measuring the changes in electric potential due to changes in the interfacial electric field. Predictive modelling of this response caused by surface binding of biomolecules remains highly challenging. In this work, through the most extensive molecular dynamics simulation of the silica-water interfacial potential and electric field to date, we report a novel prediction and explanation of the effects of nano-morphology on sensor response. Amorphous silica demonstrated a larger potentiometric response than an equivalent crystalline silica model due to increased sodium adsorption, in agreement with experiments showing improved sensor response with nano-texturing. We provide proof-of-concept that molecular dynamics can be used as a complementary tool for potentiometric biosensor response prediction. Effects that are conventionally neglected, such as surface morphology, water polarisation, biomolecule dynamics and finite-size effects, are explicitly modelled.

Plant-parasitic nematodes: towards understanding molecular players in stress responses.

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Gillet, François-Xavier; Bournaud, Caroline; Antonino de Souza Júnior, Jose Dijair; Grossi-de-Sa, Maria Fatima

2017-03-01

Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence. Nematodes trigger crucial regulatory cytoprotective mechanisms, including antioxidant and detoxification pathways. Knowledge of the upstream regulatory components that contribute to both of these pathways in PPNs remains elusive. In this review, we discuss how PPNs probably orchestrate cytoprotection to resist plant immune responses, postulating that it may be derived from ancient molecular mechanisms. The review focuses on two transcription factors, DAF-16 and SKN-1 , which are conserved in the animal kingdom and are central regulators of cell homeostasis and immune function. Both regulate the unfolding protein response and the antioxidant and detoxification pathways. DAF-16 and SKN-1 target a broad spectrum of Caenorhabditis elegans genes coding for numerous protein families present in the secretome of PPNs. Moreover, some regulatory elements of DAF-16 and SKN-1 from C. elegans have already been identified as important genes for PPN infection. DAF-16 and SKN-1 genes may play a pivotal role in PPNs during parasitism. In the context of their hub status and mode of regulation, we suggest alternative strategies for control of PPNs through RNAi approaches. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

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Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

Sex, college major, and attribution of responsibility in empathic responding to persons with HIV infection.

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Bécares, Laia; Turner, Castellano

2004-10-01

This investigation studied the influence of sex, college major, and attributed responsibility on college students' empathic responding towards persons infected with HIV. We hypothesized that (1) women would score higher on empathy than men; (2) nursing and psychology majors would score higher on empathy than business and computer science majors; and (3) participants would score higher on empathy towards a target who contracted HIV through blood transfusion (presented as a Nonresponsible target) rather than through unprotected sex (presented as a Responsible target). Two hundred and fifty-eight undergraduate students (110 male, 148 female) attending a large urban university in the northeast filled out an anonymous demographic questionnaire, the Interpersonal Reactivity Index of Davis (1983), and an Empathy Reaction Scale that was developed by the authors. Results indicated a higher mean Empathy Reaction score from nursing and psychology students as compared to business and computer science students. There was no difference in Empathy Reaction scores between men and women. A higher Empathy Reaction score was found among participants who had read a diary from the target portrayed as Nonresponsible, as opposed to those who read a diary from the target portrayed as Responsible.

DAE-BRNS life sciences symposium on molecular biology of stress response and its applications

International Nuclear Information System (INIS)

2005-01-01

The world of living organisms is full of challenges from their surroundings and these organisms learn to adapt themselves to the changes - some transient and some permanent - in these surroundings. The demands on adaptability to stress are very strong for extremophiles that live in harsh conditions such as cold or hot temperatures, salinity and hyperbaric habitats. The stress could be biotic (e.g. infection or parasitism) or abiotic (e.g. temperature, light, salinity, heavy metals etc.) Evolutionarily living organisms have developed different shapes, coloration, habits etc. to survive in their habitats. The molecular mechanisms of these biological adaptations have become clearer only in recent years from the studies on the biological responses of an organism to stresses during its life time. Such responses are characterized by activation of certain genes and synthesis of proteins and metabolites, which facilitate amelioration of the stress. The molecular biology (biochemistry and genetics) of stress response is being constantly unravelled thanks to the availability of highly sensitive and high throughput techniques and a plethora of extremophilic experimental systems such as archaebacteria, radio resistant bacteria and midges, plants surviving in cold etc. An interesting outcome of this voluminous research has been the knowledge that responses to a group of stresses share common mechanisms, at least in part. This reflects the biologically conservationist trend among otherwise diverse organisms and stresses. In this symposium several papers and posters in the area of molecular biology of stress are presented in addition to some very interesting and promising-to-be informative and stimulating plenary lectures and invited talks from highly reputed scientists. The papers relevant to INIS are indexed separately

Student Response to Tuition Increase by Academic Majors: Empirical Grounds for a Cost-Related Tuition Policy

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Shin, Jung Cheol; Milton, Sande

2008-01-01

This study explored the responses of students in different academic majors to tuition increase, with a particular focus on the relationship between tuition increase, and future earnings and college expenditures. We analyzed effects of tuition increase on enrollment in six academic majors--Engineering, Physics, Biology, Mathematics, Business, and…

Blocking junctional adhesion molecule C enhances dendritic cell migration and boosts the immune responses against Leishmania major.

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Romain Ballet

2014-12-01

Full Text Available The recruitment of dendritic cells to sites of infections and their migration to lymph nodes is fundamental for antigen processing and presentation to T cells. In the present study, we showed that antibody blockade of junctional adhesion molecule C (JAM-C on endothelial cells removed JAM-C away from junctions and increased vascular permeability after L. major infection. This has multiple consequences on the output of the immune response. In resistant C57BL/6 and susceptible BALB/c mice, we found higher numbers of innate immune cells migrating from blood to the site of infection. The subsequent migration of dendritic cells (DCs from the skin to the draining lymph node was also improved, thereby boosting the induction of the adaptive immune response. In C57BL/6 mice, JAM-C blockade after L. major injection led to an enhanced IFN-γ dominated T helper 1 (Th1 response with reduced skin lesions and parasite burden. Conversely, anti JAM-C treatment increased the IL-4-driven T helper 2 (Th2 response in BALB/c mice with disease exacerbation. Overall, our results show that JAM-C blockade can finely-tune the innate cell migration and accelerate the consequent immune response to L. major without changing the type of the T helper cell response.

Real-Time Molecular Monitoring of Chemical Environment in ObligateAnaerobes during Oxygen Adaptive Response

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Holman, Hoi-Ying N.; Wozei, Eleanor; Lin, Zhang; Comolli, Luis R.; Ball, David. A.; Borglin, Sharon; Fields, Matthew W.; Hazen, Terry C.; Downing, Kenneth H.

2009-02-25

Determining the transient chemical properties of the intracellular environment canelucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms which enable some obligate anaerobic bacteria to survive a sudden exposure to oxygen. Here we used high-resolution Fourier Transform Infrared (FTIR) spectromicroscopy to continuously follow cellular chemistry within living obligate anaerobes by monitoring hydrogen bonding in their cellular water. We observed a sequence of wellorchestrated molecular events that correspond to changes in cellular processes in those cells that survive, but only accumulation of radicals in those that do not. We thereby can interpret the adaptive response in terms of transient intracellular chemistry and link it to oxygen stress and survival. This ability to monitor chemical changes at the molecular level can yield important insights into a wide range of adaptive responses.

Molecular defense response of oil palm to Ganoderma infection.

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Ho, C-L; Tan, Y-C

2015-06-01

Basal stem rot (BSR) of oil palm roots is due to the invasion of fungal mycelia of Ganoderma species which spreads to the bole of the stem. In addition to root contact, BSR can also spread by airborne basidiospores. These fungi are able to break down cell wall components including lignin. BSR not only decreases oil yield, it also causes the stands to collapse thus causing severe economic loss to the oil palm industry. The transmission and mode of action of Ganoderma, its interactions with oil palm as a hemibiotroph, and the molecular defence responses of oil palm to the infection of Ganoderma boninense in BSR are reviewed, based on the transcript profiles of infected oil palms. The knowledge gaps that need to be filled in oil palm-Ganoderma molecular interactions i.e. the associations of hypersensitive reaction (HR)-induced cell death and reactive oxygen species (ROS) kinetics to the susceptibility of oil palm to Ganoderma spp., the interactions of phytohormones (salicylate, jasmonate and ethylene) at early and late stages of BSR, and cell wall strengthening through increased production of guaiacyl (G)-type lignin, are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular Responses of Groundnut (Arachis hypogea L. to Zinc Stress

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A. John De Britto

2013-08-01

Full Text Available Heavy metals are important environmental pollutants and their toxicity is a problem of increasing significance for ecological, evolutionary and environmental reasons. The interference of germination related proteins by heavy metals has not been well documented at the proteomic and genomic level. In the current study, molecular responses of germinating groundnut seeds were investigated under Zinc stress. The SDS-PAGE showed the preliminary changes in the polypeptides patterns under Zinc stress. Restriction digestion banding pattern of EcoRI and Hind III enzymes showed distinct banding pattern in the treated plants.

The predictive value of early molecular response in chronic myeloid leukaemia patients treated with imatinib in a single real-world medical centre in a developing country.

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Bee, Ping Chong; Sekaran, Veera; Ng, Richard Rui Jie; Kweh, Ting Yi; Gan, Gin Gin

2017-03-01

The prognosis of patients with chronic myeloid leukaemia (CML) has improved since the introduction of imatinib. However, patients who do not achieve complete cytogenetic response (CCyR) and major molecular response (MMR) have poorer prognosis. Recent clinical trials have demonstrated that early and deeper cytogenetic and molecular responses predict a better long-term outcome. This study aimed to analyse the relationship between early molecular response and clinical outcome in a real-life setting. This retrospective study included all patients with CML, in chronic or accelerated phase, who were treated with imatinib at University of Malaya Medical Centre, Malaysia. A total of 70 patients were analysed. The median follow-up duration was 74 months, and the cumulative percentages of patients with CCyR and MMR were 80.0% and 65.7%, respectively. Overall survival (OS) and event-free survival (EFS) at ten years were 94.3% and 92.9%, respectively. Patients who achieved CCyR and MMR had significantly better OS and EFS than those who did not. At six months, patients who had a BCR-ABL level ≤ 10% had significantly better OS and EFS than those who had a BCR-ABL level > 10%. The target milestone of CCyR at 12 months and MMR at 18 months showed no survival advantage in our patients. Our data showed that imatinib is still useful as first-line therapy. However, vigilant monitoring of patients who have a BCR-ABL level > 10% at six months of treatment should be implemented so that prompt action can be taken to provide the best outcome for these patients. Copyright: © Singapore Medical Association

Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches

NARCIS (Netherlands)

Denning, Denise; Roos, Wouter H

2016-01-01

The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a

Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

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Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

2017-11-01

The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Aux/IAA Gene Family in Plants: Molecular Structure, Regulation, and Function

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Jie Luo

2018-01-01

Full Text Available Auxin plays a crucial role in the diverse cellular and developmental responses of plants across their lifespan. Plants can quickly sense and respond to changes in auxin levels, and these responses involve several major classes of auxin-responsive genes, including the Auxin/Indole-3-Acetic Acid (Aux/IAA family, the auxin response factor (ARF family, small auxin upregulated RNA (SAUR, and the auxin-responsive Gretchen Hagen3 (GH3 family. Aux/IAA proteins are short-lived nuclear proteins comprising several highly conserved domains that are encoded by the auxin early response gene family. These proteins have specific domains that interact with ARFs and inhibit the transcription of genes activated by ARFs. Molecular studies have revealed that Aux/IAA family members can form diverse dimers with ARFs to regulate genes in various ways. Functional analyses of Aux/IAA family members have indicated that they have various roles in plant development, such as root development, shoot growth, and fruit ripening. In this review, recently discovered details regarding the molecular characteristics, regulation, and protein–protein interactions of the Aux/IAA proteins are discussed. These details provide new insights into the molecular basis of the Aux/IAA protein functions in plant developmental processes.

DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

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Atsushi eKamiya

2012-03-01

Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.

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van Rein, N; Biedermann, J S; van der Meer, F J M; Cannegieter, S C; Wiersma, N; Vermaas, H W; Reitsma, P H; Kruip, M J H A; Lijfering, W M

2017-07-01

Essentials Low-molecular-weight-heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once-daily dosing was associated with a lower bleeding risk as compared with twice-daily. Background Low-molecular-weight heparins (LMWHs) are considered members of a class of drugs with similar anticoagulant properties. However, pharmacodynamics and pharmacokinetics between LMWHs differ, which may result in different bleeding risks. As these agents are used by many patients, small differences may lead to a large effect on numbers of major bleeding events. Objectives To determine major bleeding risks for different LMWH agents and dosing schedules. Methods A cohort of acute venous thrombosis patients from four anticoagulation clinics who used an LMWH and a vitamin K antagonist were followed until they ceased LMWH treatment or until major bleeding. Exposures were classified according to different types of LMWHs and for b.i.d. and o.d. use. Cumulative incidences for major bleeding per 1000 patients and risk ratios were calculated and adjusted for study center. Results The study comprised 12 934 patients with a mean age of 59 years; 6218 (48%) were men. The cumulative incidence of major bleeding was 2.5 per 1000 patients (95% confidence interval [CI], 1.7-3.5). Enoxaparin b.i.d. or o.d. was associated with a relative bleeding risk of 1.7 (95% CI, 0.2-17.5) compared with nadroparin o.d. In addition, a nadroparin b.i.d. dosing schedule was associated with a 2.0-fold increased major bleeding risk (95% CI, 0.8-5.1) as compared with a nadroparin o.d. dosing schedule. Conclusions Absolute major bleeding rates were low for all LMWH agents and dosing schedules in a large unselected cohort. Nevertheless, twice-daily dosing with nadroparin appeared to be associated with an increased

Dynamic properties of sensory stimulation evoked responses in mouse cerebellar granule cell layer and molecular layer.

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Bing, Yan-Hua; Zhang, Guang-Jian; Sun, Lei; Chu, Chun-Ping; Qiu, De-Lai

2015-01-12

Sensory information coming from climbing fiber and mossy fiber-granule cell pathways, generates motor-related outputs according to internal rules of integration and computation in the cerebellar cortex. However, the dynamic properties of sensory information processing in mouse cerebellar cortex are less understood. Here, we studied the dynamic properties of sensory stimulation-evoked responses in the cerebellar granule cell layer (GCL) and molecular layer (ML) by electrophysiological recordings method. Our data showed that air-puff stimulation (5-10 ms in duration) of the ipsilateral whisker pad evoked single-peak responses in the GCL and ML; whereas a duration of stimulation ≥30 ms in GCL and ≥60 ms in ML, evoked double-peak responses that corresponded with stimulation-on and -off responses via mossy fiber pathway. The highest frequency of stimulation train for evoking GCL responses was 33 Hz. In contrast, the highest frequency of stimulation train for evoking ML responses was 4 Hz. These results indicate that the cerebellar granule cells transfer the high-fidelity sensory information from mossy fibers, which is cut-off by molecular layer interneurons (MLIs). Our results suggest that the MLIs network acts as a low-pass filter during the processing of high-frequency sensory information. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

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Lakshmanan Sannachi

Full Text Available Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS, textural analysis and molecular features in patients with locally advanced breast cancer.The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR, partial responders (PR, and non-responders (NR. Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the

Investigating the Molecular Basis of Major Depressive Disorder Etiology

NARCIS (Netherlands)

Jabbi, Mbemba; Korf, Jaalp; Ormel, Johan; Kema, Ido P.; den Boer, Johan A.; Kvetnansky, R; Aguilera, G; Goldstein, D; Jezova, D; Krizanova, O; Sabban, EL; Pacak, K

2008-01-01

Genes play a major role in behavioral adaptation to challenging environmental stimuli, but the complexity of their contribution remains unclear. There is growing evidence linking disease phenotypes with genes on the one hand, and the genesis of stress-related disorders like major depression, as a

Molecular design of light-responsive hydrogels, for in situ generation of fast and reversible valves for microfluidic applications

NARCIS (Netherlands)

Schiphorst, ter J.; Coleman, S.; Stumpel, J.E.; Ben Azouz, A.; Diamond, D.; Schenning, A.P.H.J.

2015-01-01

Reversible light-responsive hydrogel valves with response characteristics compatible for microfluidics have been obtained by optimization of molecular design of spiropyran photoswitches and gel composition. Self-protonating gel formulations were exploited, wherein acrylic acid was copolymerized in

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

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Sebastian Weckbach

2012-01-01

Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

Science.gov (United States)

Weckbach, Sebastian; Perl, Mario; Heiland, Tim; Braumüller, Sonja; Stahel, Philip F.; Flierl, Michael A.; Ignatius, Anita; Gebhard, Florian; Huber-Lang, Markus

2012-01-01

Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group) were anesthetized and exposed to chest trauma (ChT), closed head injury (CHI), or Tib/Fib fracture including a soft tissue trauma (Fx + STT) or to the following combination of injuries: (1) ChT; (2) ChT + Fx + STT; (3) ChT + CHI; (4) CHI; (5) polytrauma (PT = ChT + CHI + Fx + STT). Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL) fluid samples. Results. Polytraumatized (PT) rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma. PMID:22481866

Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.

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Kamath, Pauline L; Getz, Wayne M

2011-05-18

Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN

Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus

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Getz Wayne M

2011-05-01

Full Text Available Abstract Background Major Histocompatibility Complex (MHC genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA, DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli. We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN dS. However, the most likely evolutionary codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Conclusions Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was

Cellular and molecular responses of E. fetida coelomocytes exposed to TiO{sub 2} nanoparticles

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Bigorgne, Emilie, E-mail: emilie.bigorgne@univ-lorraine.fr; Foucaud, Laurent [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Caillet, Celine [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Giamberini, Laure; Nahmani, Johanne [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France); Thomas, Fabien [Universite de Lorraine-Laboratoire Environnement et Mineralurgie (LEM) CNRS UMR7569 (France); Rodius, Francois [Universite de Lorraine-Laboratoire des Interactions Ecotoxicologique Biodiversite Ecosystemes (LIEBE) (France)

2012-07-15

An in vitro approach using coelomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO{sub 2} nanoparticles. Coelomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO{sub 2} nanoparticles (1-25 {mu}g/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO{sub 2} nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 {mu}g/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO{sub 2} in our experimental conditions. This in vitro approach showed that TiO{sub 2} nanoparticles were taken up by coelomocytes and they could modify the molecular response of immune and detoxification system.

Advances in molecular modeling of human cytochrome P450 polymorphism.

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Martiny, Virginie Y; Miteva, Maria A

2013-11-01

Cytochrome P450 (CYP) is a supergene family of metabolizing enzymes involved in the phase I metabolism of drugs and endogenous compounds. CYP oxidation often leads to inactive drug metabolites or to highly toxic or carcinogenic metabolites involved in adverse drug reactions (ADR). During the last decade, the impact of CYP polymorphism in various drug responses and ADR has been demonstrated. Of the drugs involved in ADR, 56% are metabolized by polymorphic phase I metabolizing enzymes, 86% among them being CYP. Here, we review the major CYP polymorphic forms, their impact for drug response and current advances in molecular modeling of CYP polymorphism. We focus on recent studies exploring CYP polymorphism performed by the use of sequence-based and/or protein-structure-based computational approaches. The importance of understanding the molecular mechanisms related to CYP polymorphism and drug response at the atomic level is outlined. © 2013.

Molecular medicine: a path towards a personalized medicine.

Science.gov (United States)

Miranda, Debora Marques de; Mamede, Marcelo; Souza, Bruno Rezende de; Almeida Barros, Alexandre Guimarães de; Magno, Luiz Alexandre; Alvim-Soares, Antônio; Rosa, Daniela Valadão; Castro, Célio José de; Malloy-Diniz, Leandro; Gomez, Marcus Vinícius; Marco, Luiz Armando De; Correa, Humberto; Romano-Silva, Marco Aurélio

2012-03-01

Psychiatric disorders are among the most common human illnesses; still, the molecular and cellular mechanisms underlying their complex pathophysiology remain to be fully elucidated. Over the past 10 years, our group has been investigating the molecular abnormalities in major signaling pathways involved in psychiatric disorders. Recent evidences obtained by the Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (National Institute of Science and Technology - Molecular Medicine, INCT-MM) and others using behavioral analysis of animal models provided valuable insights into the underlying molecular alterations responsible for many complex neuropsychiatric disorders, suggesting that "defects" in critical intracellular signaling pathways have an important role in regulating neurodevelopment, as well as in pathophysiology and treatment efficacy. Resources from the INCT have allowed us to start doing research in the field of molecular imaging. Molecular imaging is a research discipline that visualizes, characterizes, and quantifies the biologic processes taking place at cellular and molecular levels in humans and other living systems through the results of image within the reality of the physiological environment. In order to recognize targets, molecular imaging applies specific instruments (e.g., PET) that enable visualization and quantification in space and in real-time of signals from molecular imaging agents. The objective of molecular medicine is to individualize treatment and improve patient care. Thus, molecular imaging is an additional tool to achieve our ultimate goal.

First molecular detection of Leishmania major within naturally infected Phlebotomus salehi from a zoonotic cutaneous leishmaniasis focus in southern Iran.

Science.gov (United States)

Azizi, K; Fakoorziba, M R; Jalali, M; Moemenbellah-Fard, M D

2012-03-01

Human cutaneous leishmaniasis (CL) is a major notifiable public health problem in many parts of Iran. It is often caused by the zooflagellate parasite Leishmania major which is mainly transmitted by the bites of female phlebotomine sandflies belonging to the genus Phlebotomus (Diptera: Psychodidae). The annual incidence of CL in Fars province, southern Iran, was about 108-144 in 2007. The leishmanial infections of wild sandflies that may act as vectors were thus investigated at an endemic focus in this province. In all 330 female Phlebotomus sandflies were screened for the detection of Leishmania-specific kinetoplast DNA (kDNA) by polymerase chain reaction (PCR) methods. A two stage nested PCR protocol was used to establish the identity of Leishmania major species in naturally infected sandflies. The L. major kDNA was detected in 18 (5.5%) individual sandflies which belonged to four different Phlebotomus species (Phlebotomus papatasi, Phlebotomus salehi, Phlebotomus sergenti and P. major group). For the first time, one naturally infected P. salehi specimen contained the kDNA of the protozoan parasite, L. major, with a main band of 560 base pairs identified using the nested PCR method. It seems most likely therefore that P. salehi is potentially a rare sylvatic vector of L. major parasites in parts of this province. This is the first combined morphological and molecular studies of P. salehi in Iran.

Molecular testing practices and perceptions among dermatopathologists.

Science.gov (United States)

Torre, Kristin; Jhorar, Preeti; Wu, Rong; Pfeifer, John; Elaba, Zendee; Murphy, Michael

2018-02-13

We evaluated how dermatopathologists are employing molecular testing in the setting of neoplastic skin diseases, and assessed their opinions of the broader role and utility of molecular technologies in clinical practice. A 15-question online survey was sent to Fellows of the American Society of Dermatopathology in April 2017. One hundred and thirty-six dermatopathologists completed the survey (response rate = 16%). A majority (94%) of respondents reported experience with one or more molecular testing strategies. Sixty-two percent of dermatopathologists order 12 or more molecular tests per year, while 5% of respondents order 2 or fewer assays per year. More frequent utilization of molecular testing is associated with relevant instruction during residency training (P = .009), primary board certification in pathology (P = .008), academic medical center affiliation (P = molecular pathology/cytogenetics laboratory (P = .007), and greater physician confidence incorporating test results into histopathological assessments (P = molecular testing in dermatopathology may be limited by factors such as physician training, test costs/insurance coverage, logistical issues and lack of evidence-based clinical practice guidelines. Dermatopathologists have concerns regarding clinical validity/utility and inappropriate/overuse of some molecular tests. The importance of longitudinal education in molecular technologies and their applications for trainee and practicing physicians is highlighted. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

National plan of response to a major nuclear or radiological accident

International Nuclear Information System (INIS)

2014-02-01

The first part of this document presents the response strategies and principles to be applied in the case of a major nuclear or radiological accident. It presents the general framework and the 8 reference situations which are used as references for the plan. It presents the general organisation of crisis management by the State (initial organisation, organisation at the national level, communication channel, international channels, case of transport of radioactive materials, responsibility of the various actors). Then, it presents the strategies of response, i.e., a global strategy and more specific strategies applicable in different sectors or fields: for the control of the concerned installation or transport, in the case of transport of radioactive materials, for the protection of the population, for the taking into care, for communication, for the continuity of social and economic life, at the European level, for the post-accidental management. The second part is a guide which contains sheets describing reactions in different situations: uncertainty, accident in an installation resulting in an either immediate and short, or immediate and long, or delayed and long release, accident in a transport of radioactive materials with potential release, accident occurring abroad which may have a more or less significant impact in France, and accident at sea

Shy and bold great tits (Parus major): body temperature and breath rate in response to handling stress

NARCIS (Netherlands)

Carere, C.; Van Oers, K.

2004-01-01

A standard handling protocol was used to test the hypothesis that boldness predicts stress responsiveness in body temperature and breath rate. Great tit (Parus major) nestlings were taken from the field, hand reared until independence, and their response to a novel object was assessed. At the age of

Shy and bold great tits (Parus major) : body temperature and breath rate in response to handling stress

NARCIS (Netherlands)

Carere, C; van Oers, K

2004-01-01

A standard handling protocol was used to test the hypothesis that boldness predicts stress responsiveness in body temperature and breath rate. Great tit (Parus major) nestlings were taken from the field, hand reared until independence, and their response to a novel object was assessed. At the age of

Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

Directory of Open Access Journals (Sweden)

Jixia Li

2013-01-01

Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

Molecular response to water stress in two contrasting Mediterranean pines (Pinus pinaster and Pinus pinea).

Science.gov (United States)

Perdiguero, Pedro; Barbero, María Del Carmen; Cervera, María Teresa; Collada, Carmen; Soto, Alvaro

2013-06-01

Adaptation to water stress has determined the evolution and diversification of vascular plants. Water stress is forecasted to increase drastically in the next decades in certain regions, such as in the Mediterranean basin. Consequently, a proper knowledge of the response and adaptations to drought stress is essential for the correct management of plant genetic resources. However, most of the advances in the understanding of the molecular response to water stress have been attained in angiosperms, and are not always applicable to gymnosperms. In this work we analyse the transcriptional response of two emblematic Mediterranean pines, Pinus pinaster and Pinus pinea, which show noticeable differences in their performance under water stress. Using microarray analysis, up to 113 genes have been detected as significantly induced by drought in both species. Reliability of expression patterns has been confirmed by RT-PCR. While induced genes with similar profiles in both species can be considered as general candidate genes for the study of drought response in conifers, genes with diverging expression patterns can underpin the differences displayed by these species under water stress. Most promising candidate genes for drought stress response include genes related to carbohydrate metabolism, such as glycosyltransferases or galactosidases, sugar transporters, dehydrins and transcription factors. Additionally, differences in the molecular response to drought and polyethylene-glycol-induced water stress are also discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Molecular Imaging of Breast Cancer: Present and future directions

Directory of Open Access Journals (Sweden)

David eAlcantara

2014-12-01

Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

Seismic safety margins research program. Phase I final report - Major structure response (Project IV)

International Nuclear Information System (INIS)

Benda, B.J.; Johnson, J.J.; Lo, T.Y.

1981-08-01

The primary task of the Major Structure Response Project within the Seismic Safety Margins Research Program (SSMRP) was to develop detailed finite element models of the Zion Nuclear Power Plant's containment building and auxiliary-fuel-turbine (AFT) complex. The resulting models served as input to the seismic methodology analysis chain. The containment shell was modeled as a series of beam elements with the shear and bending characteristics of a circular cylindrical shell. Masses and rotary inertias were lumped at nodal points; thirteen modes were included in the analysis. The internal structure was modeled with three-dimensional finite elements, with masses again lumped at selected nodes; sixty modes were included in the analysis. The model of the AFT complex employed thin plate and shell elements to represent the concrete shear walls and floor diaphragms, and beam and truss elements to model the braced frames. Because of the size and complexity of the model, and the potentially large number of degrees of freedom, masses were lumped at a limited number of node points. These points were selected so as to minimize the effect of the discrete mass distribution on structural response. One hundred and thirteen modes were extracted. A second objective of Project IV was to investigate the effects of uncertainty and variability on structural response. To this end, four side studies were conducted. Three of them, briefly summarized in this volume, addressed themselves respectively to an investigation of sources of random variability in the dynamic response of nuclear power plant structures; formulation of a methodology for modeling and evaluating the effects of structural uncertainty on predicted modal characteristics of major nuclear power plant structures and substructures; and a preliminary evaluation of nonlinear responses in shear-wall structures. A fourth side study, reported in detail in this volume, quantified variations in dynamic characteristics and seismic

Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Ingrid Leguerney

2017-01-01

Full Text Available Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87, p=0.0003 and AUC (R=0.81, p=0.0013. The percentage of vessel tissue area was significantly reduced (p<0.01 in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis

DEFF Research Database (Denmark)

Kemp, M; Hey, A S; Kurtzhals, J A

1994-01-01

of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after...... the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL...... stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from...

Increased amygdala response to shame in remitted major depressive disorder.

Directory of Open Access Journals (Sweden)

Erdem Pulcu

Full Text Available Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD, and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8. This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15. Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

Abiotic stressors and stress responses: What commonalities appear between species across biological organization levels?

International Nuclear Information System (INIS)

Sulmon, Cécile; Baaren, Joan van; Cabello-Hurtado, Francisco; Gouesbet, Gwenola; Hennion, Françoise; Mony, Cendrine; Renault, David; Bormans, Myriam; El Amrani, Abdelhak; Wiegand, Claudia; Gérard, Claudia

2015-01-01

Organisms are regularly subjected to abiotic stressors related to increasing anthropogenic activities, including chemicals and climatic changes that induce major stresses. Based on various key taxa involved in ecosystem functioning (photosynthetic microorganisms, plants, invertebrates), we review how organisms respond and adapt to chemical- and temperature-induced stresses from molecular to population level. Using field-realistic studies, our integrative analysis aims to compare i) how molecular and physiological mechanisms related to protection, repair and energy allocation can impact life history traits of stressed organisms, and ii) to what extent trait responses influence individual and population responses. Common response mechanisms are evident at molecular and cellular scales but become rather difficult to define at higher levels due to evolutionary distance and environmental complexity. We provide new insights into the understanding of the impact of molecular and cellular responses on individual and population dynamics and assess the potential related effects on communities and ecosystem functioning. - Highlights: • Responses to chemical and thermal stressors are reviewed across organization levels. • Common responses between taxa are evident at the molecular and cellular scales. • At individual level, energy allocation connects species-specific stress responses. • Commonality decreases at higher levels due to increasing environmental complexity. - The commonality of stress responses to chemical and thermal stressors among taxa is evident at the molecular and cellular scales but remains unclear at higher levels of organization

Contraction of online response to major events.

Science.gov (United States)

Szell, Michael; Grauwin, Sébastian; Ratti, Carlo

2014-01-01

Quantifying regularities in behavioral dynamics is of crucial interest for understanding collective social events such as panics or political revolutions. With the widespread use of digital communication media it has become possible to study massive data streams of user-created content in which individuals express their sentiments, often towards a specific topic. Here we investigate messages from various online media created in response to major, collectively followed events such as sport tournaments, presidential elections, or a large snow storm. We relate content length and message rate, and find a systematic correlation during events which can be described by a power law relation--the higher the excitation, the shorter the messages. We show that on the one hand this effect can be observed in the behavior of most regular users, and on the other hand is accentuated by the engagement of additional user demographics who only post during phases of high collective activity. Further, we identify the distributions of content lengths as lognormals in line with statistical linguistics, and suggest a phenomenological law for the systematic dependence of the message rate to the lognormal mean parameter. Our measurements have practical implications for the design of micro-blogging and messaging services. In the case of the existing service Twitter, we show that the imposed limit of 140 characters per message currently leads to a substantial fraction of possibly dissatisfying to compose tweets that need to be truncated by their users.

Contraction of online response to major events.

Directory of Open Access Journals (Sweden)

Michael Szell

Full Text Available Quantifying regularities in behavioral dynamics is of crucial interest for understanding collective social events such as panics or political revolutions. With the widespread use of digital communication media it has become possible to study massive data streams of user-created content in which individuals express their sentiments, often towards a specific topic. Here we investigate messages from various online media created in response to major, collectively followed events such as sport tournaments, presidential elections, or a large snow storm. We relate content length and message rate, and find a systematic correlation during events which can be described by a power law relation--the higher the excitation, the shorter the messages. We show that on the one hand this effect can be observed in the behavior of most regular users, and on the other hand is accentuated by the engagement of additional user demographics who only post during phases of high collective activity. Further, we identify the distributions of content lengths as lognormals in line with statistical linguistics, and suggest a phenomenological law for the systematic dependence of the message rate to the lognormal mean parameter. Our measurements have practical implications for the design of micro-blogging and messaging services. In the case of the existing service Twitter, we show that the imposed limit of 140 characters per message currently leads to a substantial fraction of possibly dissatisfying to compose tweets that need to be truncated by their users.

Molecular imaging in the era of personalized medicine.

Science.gov (United States)

Jung, Kyung-Ho; Lee, Kyung-Han

2015-01-01

Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

Unravelling molecular responses to moderate dehydration in harvested fruit of sweet orange (Citrus sinensis L. Osbeck) using a fruit-specific ABA-deficient mutant.

Science.gov (United States)

Romero, Paco; Rodrigo, María J; Alférez, Fernando; Ballester, Ana-Rosa; González-Candelas, Luis; Zacarías, Lorenzo; Lafuente, María T

2012-04-01

Water stress affects many agronomic traits that may be regulated by the phytohormone abscisic acid (ABA). Within these traits, loss of fruit quality becomes important in many citrus cultivars that develop peel damage in response to dehydration. To study peel dehydration transcriptional responsiveness in harvested citrus fruit and the putative role of ABA in this process, this study performed a comparative large-scale transcriptional analysis of water-stressed fruits of the wild-type Navelate orange (Citrus sinesis L. Osbeck) and its spontaneous ABA-deficient mutant Pinalate, which is more prone to dehydration and to developing peel damage. Major changes in gene expression occurring in the wild-type line were impaired in the mutant fruit. Gene ontology analysis revealed the ability of Navelate fruits to induce the response to water deprivation and di-, tri-valent inorganic cation transport biological processes, as well as repression of the carbohydrate biosynthesis process in the mutant. Exogenous ABA triggered relevant transcriptional changes and repressed the protein ubiquitination process, although it could not fully rescue the physiological behaviour of the mutant. Overall, the results indicated that dehydration responsiveness requires ABA-dependent and -independent signals, and highlight that the ability of citrus fruits to trigger molecular responses against dehydration is an important factor in reducing their susceptibility to developing peel damage.

Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots affected by apple replant disease.

Science.gov (United States)

Weiß, Stefan; Bartsch, Melanie; Winkelmann, Traud

2017-06-01

Gene expression studies in roots of apple replant disease affected plants suggested defense reactions towards biotic stress to occur which did not lead to adequate responses to the biotic stressors. Apple replant disease (ARD) leads to growth inhibition and fruit yield reduction in replanted populations and results in economic losses for tree nurseries and fruit producers. The etiology is not well understood on a molecular level and causal agents show a great diversity indicating that no definitive cause, which applies to the majority of cases, has been found out yet. Hence, it is pivotal to gain a better understanding of the molecular and physiological reactions of the plant when affected by ARD and later to overcome the disease, for example by developing tolerant rootstocks. For the first time, gene expression was investigated in roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as plant defense, regulatory and signaling genes were upregulated whereas for several genes involved in primary metabolism lower expression was detected. For internal verification of MACE data, candidate genes were tested via RT-qPCR and a strong positive correlation between both datasets was observed. Comparison of apple 'M26' roots cultivated in ARD soil or γ-irradiated ARD soil suggests that typical defense reactions towards biotic stress take place in ARD affected plants but they did not allow responding to the biotic stressors attack adequately, leading to the observed growth depressions in ARD variants.

Molecular regulation of plant cell wall extensibility

Science.gov (United States)

Cosgrove, D. J.

1998-01-01

Gravity responses in plants often involve spatial and temporal changes in cell growth, which is regulated primarily by controlling the ability of the cell wall to extend. The wall is thought to be a cellulose-hemicellulose network embedded in a hydrated matrix of complex polysaccharides and a small amount of structural protein. The wall extends by a form of polymer creep, which is mediated by expansins, a novel group of wall-loosening proteins. Expansins were discovered during a molecular dissection of the "acid growth" behavior of cell walls. Expansin alters the rheology of plant walls in profound ways, yet its molecular mechanism of action is still uncertain. It lacks detectable hydrolytic activity against the major components of the wall, but it is able to disrupt noncovalent adhesion between wall polysaccharides. The discovery of a second family of expansins (beta-expansins) sheds light on the biological role of a major group of pollen allergens and implies that expansins have evolved for diverse developmental functions. Finally, the contribution of other processes to wall extensibility is briefly summarized.

Cellular and molecular responses of E. fetida cœlomocytes exposed to TiO2 nanoparticles

Science.gov (United States)

Bigorgne, Emilie; Foucaud, Laurent; Caillet, Céline; Giambérini, Laure; Nahmani, Johanne; Thomas, Fabien; Rodius, François

2012-07-01

An in vitro approach using cœlomocytes of Eisenia fetida was investigated to evaluate toxicity of TiO2 nanoparticles. Cœlomocytes were exposed to well-dispersed suspension of small aggregates (130 nm) of TiO2 nanoparticles (1-25 μg/ml) during 4, 12 and 24 h. Intracellular localisation suggested that the main route of uptake was endocytosis. Cellular responses showed that TiO2 nanoparticles were not cytotoxic and had no effect on phagocytosis at any of the four concentrations for each time tested. Concerning molecular responses, an increase of fetidin and metallothionein mRNA expression was observed starting from 4 h of exposure. In contrast, expression of coelomic cytolytic factor mRNA decreased for 10 and 25 μg/ml after 4 h. Superoxide dismutase, catalase and glutathione-S-transferase expression were not modified suggesting that oxidative stress was not induced by TiO2 in our experimental conditions. This in vitro approach showed that TiO2 nanoparticles were taken up by cœlomocytes and they could modify the molecular response of immune and detoxification system.

Molecular characterization and expression profiling of cd-responsive genes in triticum durum

OpenAIRE

Cebeci, Özge; Cebeci, Ozge

2006-01-01

Cadmium (Cd) is a toxic heavy metal which has detrimental effects both in plants and human. There is a lack of knowledge on the molecular mechanisms of Cd toxicity in crop plants. The objective of this study was to identify and clone expressed Cd-responsive genes from two Triticum durum cvs. Balcah-85 and Balcah-2000 using mRNA differential display technique. We identified 10 cDNA clones whose level of expression significantly changed upon Cd exposure and thus isolated for further characteriz...

Reviewing and Updating the Major Molecular Markers for Stem Cells

Science.gov (United States)

Calloni, Raquel; Cordero, Elvira Alicia Aparicio; Henriques, João Antonio Pêgas

2013-01-01

Stem cells (SC) are able to self-renew and to differentiate into many types of committed cells, making SCs interesting for cellular therapy. However, the pool of SCs in vivo and in vitro consists of a mix of cells at several stages of differentiation, making it difficult to obtain a homogeneous population of SCs for research. Therefore, it is important to isolate and characterize unambiguous molecular markers that can be applied to SCs. Here, we review classical and new candidate molecular markers that have been established to show a molecular profile for human embryonic stem cells (hESCs), mesenchymal stem cells (MSCs), and hematopoietic stem cells (HSCs). The commonly cited markers for embryonic ESCs are Nanog, Oct-4, Sox-2, Rex-1, Dnmt3b, Lin-28, Tdgf1, FoxD3, Tert, Utf-1, Gal, Cx43, Gdf3, Gtcm1, Terf1, Terf2, Lefty A, and Lefty B. MSCs are primarily identified by the expression of CD13, CD29, CD44, CD49e, CD54, CD71, CD73, CD90, CD105, CD106, CD166, and HLA-ABC and lack CD14, CD31, CD34, CD45, CD62E, CD62L, CD62P, and HLA-DR expression. HSCs are mainly isolated based on the expression of CD34, but the combination of this marker with CD133 and CD90, together with a lack of CD38 and other lineage markers, provides the most homogeneous pool of SCs. Here, we present new and alternative markers for SCs, along with microRNA profiles, for these cells. PMID:23336433

Higher Plants in Space: Microgravity Perception, Response, and Adaptation

Science.gov (United States)

Zheng, Hui Qiong; Han, Fei; Le, Jie

2015-11-01

Microgravity is a major abiotic stress in space. Its effects on plants may depend on the duration of exposure. We focused on two different phases of microgravity responses in space. When higher plants are exposed to short-term (seconds to hours) microgravity, such as on board parabolic flights and sounding rockets, their cells usually exhibit abiotic stress responses. For example, Ca 2+-, lipid-, and pH-signaling are rapidly enhanced, then the production of reactive oxygen species and other radicals increase dramatically along with changes in metabolism and auxin signaling. Under long-term (days to months) microgravity exposure, plants acclimatize to the stress by changing their metabolism and oxidative response and by enhancing other tropic responses. We conclude by suggesting that a systematic analysis of regulatory networks at the molecular level of higher plants is needed to understand the molecular signals in the distinct phases of the microgravity response and adaptation.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

International Nuclear Information System (INIS)

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research

Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

Directory of Open Access Journals (Sweden)

Carola Rong

2018-04-01

Full Text Available Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD symptoms as a part of major depressive disorder (MDD and bipolar disorder (BD. The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. Method: Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI, history of suicide, family history of alcohol use disorder, peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels, polysomnography (abnormalities in delta sleep ratio, neurochemistry (i.e., glutamine/glutamate ratio, neuroimaging (i.e., anterior cingulate cortex activity, genetic variation (i.e., Val66Met BDNF allele, and cognitive functioning (i.e., processing speed. High BMI and a positive family history of alcohol use disorder were the most replicated predictors. Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

Molecular and biochemical responses of hypoxia exposure in Atlantic croaker collected from hypoxic regions in the northern Gulf of Mexico.

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Rahman, Md Saydur; Thomas, Peter

2017-01-01

A major impact of global climate change has been the marked increase worldwide in the incidence of coastal hypoxia (dissolved oxygen, DOhypoxic waters as well as their molecular and physiological responses to environmental hypoxia exposure are largely unknown. A suite of potential hypoxia exposure biomarkers was evaluated in Atlantic croaker collected from hypoxic and normoxic regions in the northern Gulf of Mexico (nGOM), and in croaker after laboratory exposure to hypoxia (DO: 1.7 mg l-1). Expression of hypoxia-inducible factor-α, hif-α; neuronal nitric oxide synthase, nNOS; and insulin-like growth factor binding protein, igfbp mRNAs and protein carbonyl (PC, an oxidative stress indicator) content were elevated several-fold in brain and liver tissues of croaker collected from nGOM hypoxic sites. All of these molecular and biochemical biomarkers were also upregulated ~3-10-fold in croaker brain and liver tissues within 1-2 days of hypoxia exposure in controlled laboratory experiments. These results suggest that hif-αs, nNOS and igfbp-1 transcripts and PC contents are useful biomarkers of environmental hypoxia exposure and some of its physiological effects, making them important components for improved assessments of long-term impacts of environmental hypoxia on fish populations.

Tailored Surfaces/Assemblies for Molecular Plasmonics and Plasmonic Molecular Electronics.

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Lacroix, Jean-Christophe; Martin, Pascal; Lacaze, Pierre-Camille

2017-06-12

Molecular plasmonics uses and explores molecule-plasmon interactions on metal nanostructures for spectroscopic, nanophotonic, and nanoelectronic devices. This review focuses on tailored surfaces/assemblies for molecular plasmonics and describes active molecular plasmonic devices in which functional molecules and polymers change their structural, electrical, and/or optical properties in response to external stimuli and that can dynamically tune the plasmonic properties. We also explore an emerging research field combining molecular plasmonics and molecular electronics.

Molecular mechanism of Mg2+-dependent gating in CorA

Science.gov (United States)

Dalmas, Olivier; Sompornpisut, Pornthep; Bezanilla, Francisco; Perozo, Eduardo

2014-04-01

CorA is the major transport system responsible for Mg2+ uptake in bacteria and can functionally substitute for its homologue Mrs2p in the yeast inner mitochondrial membrane. Although several CorA crystal structures are available, the molecular mechanism of Mg2+ uptake remains to be established. Here we use electron paramagnetic resonance spectroscopy, electrophysiology and molecular dynamic simulations to show that CorA is regulated by cytoplasmic Mg2+ acting as a ligand and elucidate the basic conformational rearrangements responsible for Mg2+-dependent gating. Mg2+ unbinding at the divalent cation sensor triggers a conformational change that leads to the inward motion of the stalk helix, which propagates to the pore-forming transmembrane helix TM1. Helical tilting and rotation in TM1 generates an iris-like motion that increases the diameter of the permeation pathway, triggering ion conduction. This work establishes the molecular basis of a Mg2+-driven negative feedback loop in CorA as the key physiological event controlling Mg2+ uptake and homeostasis in prokaryotes.

Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

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Martino V. Franchi

2017-07-01

Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

Engineering responsive polymer building blocks with host-guest molecular recognition for functional applications.

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Hu, Jinming; Liu, Shiyong

2014-07-15

CONSPECTUS: All living organisms and soft matter are intrinsically responsive and adaptive to external stimuli. Inspired by this fact, tremendous effort aiming to emulate subtle responsive features exhibited by nature has spurred the invention of a diverse range of responsive polymeric materials. Conventional stimuli-responsive polymers are constructed via covalent bonds and can undergo reversible or irreversible changes in chemical structures, physicochemical properties, or both in response to a variety of external stimuli. They have been imparted with a variety of emerging applications including drug and gene delivery, optical sensing and imaging, diagnostics and therapies, smart coatings and textiles, and tissue engineering. On the other hand, in comparison with molecular chemistry held by covalent bonds, supramolecular chemistry built on weak and reversible noncovalent interactions has emerged as a powerful and versatile strategy for materials fabrication due to its facile accessibility, extraordinary reversibility and adaptivity, and potent applications in diverse fields. Typically involving more than one type of noncovalent interactions (e.g., hydrogen bonding, metal coordination, hydrophobic association, electrostatic interactions, van der Waals forces, and π-π stacking), host-guest recognition refers to the formation of supramolecular inclusion complexes between two or more entities connected together in a highly controlled and cooperative manner. The inherently reversible and adaptive nature of host-guest molecular recognition chemistry, stemming from multiple noncovalent interactions, has opened up a new platform to construct novel types of stimuli-responsive materials. The introduction of host-guest chemistry not only enriches the realm of responsive materials but also confers them with promising new applications. Most intriguingly, the integration of responsive polymer building blocks with host-guest recognition motifs will endow the former with

Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study.

Science.gov (United States)

Martinez-Lopez, Joaquin; Fernández-Redondo, Elena; García-Sánz, Ramón; Montalbán, María Angeles; Martínez-Sánchez, Pilar; Pavia, Bruno; Mateos, María Victoria; Rosiñol, Laura; Martín, Marisa; Ayala, Rosa; Martínez, Rafael; Blanchard, María Jesus; Alegre, Adrian; Besalduch, Joan; Bargay, Joan; Hernandez, Miguel T; Sarasquete, María Eugenia; Sanchez-Godoy, Pedro; Fernández, Manuela; Blade, Joan; San Miguel, Jesús F; Lahuerta, Juan Jose

2013-12-01

Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM. © 2013 John Wiley & Sons Ltd.

Molecular markers in bladder cancer: Novel research frontiers.

Science.gov (United States)

Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

2015-01-01

Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

A novel heat shock protein alpha 8 (Hspa8) molecular network mediating responses to stress- and ethanol-related behaviors.

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Urquhart, Kyle R; Zhao, Yinghong; Baker, Jessica A; Lu, Ye; Yan, Lei; Cook, Melloni N; Jones, Byron C; Hamre, Kristin M; Lu, Lu

2016-04-01

Genetic differences mediate individual differences in susceptibility and responses to stress and ethanol, although, the specific molecular pathways that control these responses are not fully understood. Heat shock protein alpha 8 (Hspa8) is a molecular chaperone and member of the heat shock protein family that plays an integral role in the stress response and that has been implicated as an ethanol-responsive gene. Therefore, we assessed its role in mediating responses to stress and ethanol across varying genetic backgrounds. The hippocampus is an important mediator of these responses, and thus, was examined in the BXD family of mice in this study. We conducted bioinformatic analyses to dissect genetic factors modulating Hspa8 expression, identify downstream targets of Hspa8, and examined its role. Hspa8 is trans-regulated by a gene or genes on chromosome 14 and is part of a molecular network that regulates stress- and ethanol-related behaviors. To determine additional components of this network, we identified direct or indirect targets of Hspa8 and show that these genes, as predicted, participate in processes such as protein folding and organic substance metabolic processes. Two phenotypes that map to the Hspa8 locus are anxiety-related and numerous other anxiety- and/or ethanol-related behaviors significantly correlate with Hspa8 expression. To more directly assay this relationship, we examined differences in gene expression following exposure to stress or alcohol and showed treatment-related differential expression of Hspa8 and a subset of the members of its network. Our findings suggest that Hspa8 plays a vital role in genetic differences in responses to stress and ethanol and their interactions.

The peri-operative cytokine response in infants and young children following major surgery

DEFF Research Database (Denmark)

Hansen, Tom Giedsing; Tønnesen, Else Kirstine; Andersen, J B

1998-01-01

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were...... taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10...... and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early...

Murine immune response induced by Leishmania major during the implantation of paraffin tablets.

Science.gov (United States)

Reis, Maria Letícia Costa; Ferreira, Vanessa Martins; Zhang, Xia; Gonçalves, Ricardo; Vieira, Leda Quércia; Tafuri, Washington Luiz; Mosser, David M; Tafuri, Wagner Luiz

2010-11-01

We carried out a model of chronic inflammation using a subcutaneous paraffin tablet in mice experimentally infected with Leishmania major. It was previously reported that the parasite load following paraffin implantation occurred at a peak of 21 days in both BALB/c and C57BL/6 mice. At the present study, we have investigated what cytokines and chemokines are directly related to the parasite load in C57BL/6 mice. All mice were divided in four groups: mice implanted with paraffin tablets; mice experimentally infected with L. major; mice implanted with paraffin tablets and experimentally infected with L. major; and mice submitted only to the surgery were used for the Real-Time Polymerase Chain Reaction (RT-PCR) controls. Fragments of skin tissue and the tissue surrounding the paraffin tablets (inflammatory capsule) were collected for histopathology and RT-PCR studies. By 21 days, a diffuse chronic inflammatory reaction was mainly observed in the deep dermis where macrophages parasitized with Leishmania amastigotes were also found. RT-PCR analysis has shown that BALB/c mice showed strong IL-4 and IL-10 mRNA expression than controls with very little expression of IFN-γ. In contrast, both IFN-γ and IL-10 mRNA was found in higher levels in C57BL/6 animals. Moreover, in C57BL/6 mice the expression of chemokines mRNA of CCL3/MIP-1α was more highly expressed than CCL2/MCP-1. We conclude that the Th1 immune response C57BL/6 did not change to a Th2 response, even though C57BL/6 animals presented higher parasitism than BALB/c mice 21 days after infection and paraffin implantation.

Molecular responses during cadmium-induced stress in Daphnia magna: Integration of differential gene expression with higher-level effects

Energy Technology Data Exchange (ETDEWEB)

Soetaert, Anneleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)]. E-mail: anneleen.soetaert@ua.ac.be; Vandenbrouck, Tine [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Ven, Karlijn van der [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Maras, Marleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Remortel, Piet van [Department of Mathematics and Informatics, Intelligent Systems Laboratory, University of Antwerp, Middelheimlaan 1, B-2020 Antwerp (Belgium); Blust, Ronny [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Coen, Wim M. de [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

2007-07-20

DNA microarrays offer great potential in revealing insight into mechanistic toxicity of contaminants. The aim of the present study was (i) to gain insight in concentration- and time-dependent cadmium-induced molecular responses by using a customized Daphnia magna microarray, and (ii) to compare the gene expression profiles with effects at higher levels of biological organization (e.g. total energy budget and growth). Daphnids were exposed to three cadmium concentrations (nominal value of 10, 50, 100 {mu}g/l) for two time intervals (48 and 96 h). In general, dynamic expression patterns were obtained with a clear increase of gene expression changes at higher concentrations and longer exposure duration. Microarray analysis revealed cadmium affected molecular pathways associated with processes such as digestion, oxygen transport, cuticula metabolism and embryo development. These effects were compared with higher-level effects (energy budgets and growth). For instance, next to reduced energy budgets due to a decline in lipid, carbohydrate and protein content, we found an up-regulated expression of genes related to digestive processes (e.g. {alpha}-esterase, cellulase, {alpha}-amylase). Furthermore, cadmium affected the expression of genes coding for proteins involved in molecular pathways associated with immune response, stress response, cell adhesion, visual perception and signal transduction in the present study.

Major depressive disorder and generalized anxiety disorder and response to treatment in hepatitis C patients in Egypt.

Science.gov (United States)

MM, Bassiony; A, Yousef; U, Youssef; GM, Salah El-Deen; M, Abdelghani; H, Al-Gohari; E, Fouad; MM, El-Shafaey

2015-01-01

The aim of the study was to estimate the prevalence and associated correlates of major depressive disorder and generalized anxiety disorder in hepatitis C virus patients before and after treatment and to investigate the relationship between major depressive disorder and generalized anxiety disorder and treatment response. A total of 116 consecutive hepatitis C virus patients from hepatitis C virus treatment center in Zagazig city, Egypt, were included in the study and divided into treated group (N = 58) and untreated group (N = 58). All hepatitis C virus patients were screened for major depressive disorder and generalized anxiety disorder using hospital anxiety and depression scale, and those who screened positive were interviewed to confirm the diagnosis of major depressive disorder and generalized anxiety disorder using DSM-IV-TR diagnostic criteria. These measures were done at baseline and after 12 weeks of treatment or observation. At baseline, 3.5% and 12.1% of hepatitis C virus patients (treated group) had major depressive disorder and generalized anxiety disorder, respectively. After 12 weeks of treatment 37.9% of hepatitis C virus patients (treated group) had major depressive disorder and 46.6% had generalized anxiety disorder. There was a significant statistical difference between hospital anxiety and depression scale scores for depression (3.3 ± 2.3 vs. 6.4 ± 3.2, t = 9.6, p = 0.001) and for anxiety (4.6 ± 2.4 vs. 7.3 ± 3.0, t = 10.2, p = 0.001) before and after treatment. There was also significant statistical difference between treated group and untreated group regarding hospital anxiety and depression scale scores after treatment and observation (depression, treated group 6.4 ± 3.2 vs. untreated group 4.0 ± 2.4, t = 3.7, p = 0.001; anxiety, treated group 7.3 ± 3.0 vs. untreated group 4.5 ± 2.3, t = 4.4, p = 0.001). There was no association between major depressive disorder

Molecular identification and population dynamics of the major ...

African Journals Online (AJOL)

Adult female mosquito vectors were collected from three villages in a typical rain forest area of Nigeria where no information exists on the major malaria vectors associated with human malaria. Sampling was carried out between January 2004 and January 2005 using pyrethrum and Human landing catch (HLC) techniques.

Analysis of Microbe-Associated Molecular Pattern-Responsive Synthetic Promoters with the Parsley Protoplast System.

Science.gov (United States)

Kanofsky, Konstantin; Lehmeyer, Mona; Schulze, Jutta; Hehl, Reinhard

2016-01-01

Plants recognize pathogens by microbe-associated molecular patterns (MAMPs) and subsequently induce an immune response. The regulation of gene expression during the immune response depends largely on cis-sequences conserved in promoters of MAMP-responsive genes. These cis-sequences can be analyzed by constructing synthetic promoters linked to a reporter gene and by testing these constructs in transient expression systems. Here, the use of the parsley (Petroselinum crispum) protoplast system for analyzing MAMP-responsive synthetic promoters is described. The synthetic promoter consists of four copies of a potential MAMP-responsive cis-sequence cloned upstream of a minimal promoter and the uidA reporter gene. The reporter plasmid contains a second reporter gene, which is constitutively expressed and hence eliminates the requirement of a second plasmid used as a transformation control. The reporter plasmid is transformed into parsley protoplasts that are elicited by the MAMP Pep25. The MAMP responsiveness is validated by comparing the reporter gene activity from MAMP-treated and untreated cells and by normalizing reporter gene activity using the constitutively expressed reporter gene.

Enhancement of human adaptive immune responses by administration of a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis

DEFF Research Database (Denmark)

Pedersen, Morten Løbner; Walsted, Anette; Larsen, Rune

2008-01-01

The effect of consumption of Immulina, a high-molecular-weight polysaccharide extract from the cyanobacterium Arthrospira platensis, on adaptive immune responses was investigated by evaluation of changes in leukocyte responsiveness to two foreign recall antigens, Candida albicans (CA) and tetanus...

Molecular Genotyping of Giardia duodenalis Isolates from Symptomatic Individuals Attending Two Major Public Hospitals in Madrid, Spain.

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Aida de Lucio

Full Text Available The flagellate protozoan Giardia duodenalis is an enteric parasite causing human giardiasis, a major gastrointestinal disease of global distribution affecting both developing and industrialised countries. In Spain, sporadic cases of giardiasis have been regularly identified, particularly in pediatric and immigrant populations. However, there is limited information on the genetic variability of circulating G. duodenalis isolates in the country.In this longitudinal molecular epidemiological study we report the diversity and frequency of the G. duodenalis assemblages and sub-assemblages identified in 199 stool samples collected from 184 individual with symptoms compatible with giardiasis presenting to two major public hospitals in Madrid for the period December 2013-January 2015. G. duodenalis cysts were initially detected by conventional microscopy and/or immunochomatography on stool samples. Confirmation of the infection was performed by direct immunofluorescence and real-time PCR methods. G. duodenalis assemblages and sub-assemblages were determined by multi-locus genotyping of the glutamate dehydrogenase (GDH and β-giardin (BG genes of the parasite. Sociodemographic and clinical features of patients infected with G. duodenalis were also analysed.Of 188 confirmed positive samples from 178 giardiasis cases a total of 124 G. duodenalis isolates were successfully typed at the GDH and/or the BG loci, revealing the presence of sub-assemblages BIV (62.1%, AII (15.3%, BIII (4.0%, AI (0.8%, and AIII (0.8%. Additionally, 6.5% of the isolates were only characterised at the assemblage level, being all of them assigned to assemblage B. Discordant genotype results AII/AIII or BIII/BIV were also observed in 10.5% of DNA isolates. A large number of multi-locus genotypes were identified in G. duodenalis assemblage B, but not assemblage A, isolates at both the GDH and BG loci, confirming the high degree of genetic variability observed in other molecular surveys

Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

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Qingqing Meng

2013-01-01

Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

Science.gov (United States)

Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

2014-05-07

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely

Response conflict and frontocingulate dysfunction in unmedicated participants with major depression.

Science.gov (United States)

Holmes, Avram J; Pizzagalli, Diego A

2008-10-01

Individuals with major depressive disorder (MDD) often exhibit impaired executive function, particularly in experimental tasks that involve response conflict and require adaptive behavioral adjustments. Prior research suggests that these deficits might be due to dysfunction within frontocingulate pathways implicated in response conflict monitoring and the recruitment of cognitive control. However, the temporal unfolding of conflict monitoring impairments in MDD remains poorly understood. To address this issue, we recorded 128-channel event-related potentials while 20 unmedicated participants with MDD and 20 demographically matched, healthy controls performed a Stroop task. Compared to healthy controls, MDD subjects showed larger Stroop interference effects and reduced N2 and N450 amplitudes. Source localization analyses at the time of maximal N450 activity revealed that MDD subjects had significantly reduced dorsal anterior cingulate cortex (dACC; Brodmann area 24/32) and left dorsolateral prefrontal cortex (Brodmann area 10/46) activation to incongruent relative to congruent trials. Consistent with the heterogeneous nature of depression, follow-up analyses revealed that depressed participants with the lowest level of conflict-related dACC activation 620 ms post-stimulus were characterized by the largest Stroop interference effects (relatively increased slowing and reduced accuracy for incongruent trials). Conversely, MDD participants with relatively stronger dACC recruitment did not differ from controls in terms of interference effects. These findings suggest that for some, but not all individuals, MDD is associated with impaired performance in trials involving competition among different response options, and reduced recruitment of frontocingulate pathways implicated in conflict monitoring and cognitive control.

Individual vs. combinatorial effect of elevated CO2 conditions and salinity stress on Arabidopsis thaliana liquid cultures: Comparing the early molecular response using time-series transcriptomic and metabolomic analyses

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Dutta Bhaskar

2010-12-01

Full Text Available Abstract Background In this study, we investigated the individual and combinatorial effect of elevated CO2 conditions and salinity stress on the dynamics of both the transcriptional and metabolic physiology of Arabidopsis thaliana liquid hydroponic cultures over the first 30 hours of continuous treatment. Both perturbations are of particular interest in plant and agro-biotechnological applications. Moreover, within the timeframe of this experiment, they are expected to affect plant growth to opposite directions. Thus, a major objective was to investigate whether this expected "divergence" was valid for the individual perturbations and to study how it is manifested under the combined stress at two molecular levels of cellular function, using high-throughput analyses. Results We observed that a high salinity has stronger effect than elevated CO2 at both the transcriptional and metabolic levels, b the transcriptional responses to the salinity and combined stresses exhibit strong similarity, implying a robust transcriptional machinery acting to the salinity stress independent of the co-occurrence of elevated CO2, c the combinatorial effect of the two perturbations on the metabolic physiology is milder than of the salinity stress alone. Metabolomic analysis suggested that the beneficial role of elevated CO2 on salt-stressed plants within the timeframe of this study should be attributed to the provided additional resources; these allow the plants to respond to high salinity without having to forfeit other major metabolic functions, and d 9 h-12 h and 24 h of treatment coincide with significant changes in the metabolic physiology under any of the investigated stresses. Significant differences between the acute and longer term responses were observed at both molecular levels. Conclusions This study contributes large-scale dynamic omic data from two levels of cellular function for a plant system under various stresses. It provides an additional example

The Impact of Two Different Transfusion Strategies on Patient Immune Response during Major Abdominal Surgery: A Preliminary Report

OpenAIRE

Theodoraki, Kassiani; Markatou, Maria; Rizos, Demetrios; Fassoulaki, Argyro

2014-01-01

Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped be...

Lipidomic Adaptations in White and Brown Adipose Tissue in Response to Exercise Demonstrate Molecular Species-Specific Remodeling

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Francis J. May

2017-02-01

Full Text Available Exercise improves whole-body metabolic health through adaptations to various tissues, including adipose tissue, but the effects of exercise training on the lipidome of white adipose tissue (WAT and brown adipose tissue (BAT are unknown. Here, we utilize MS/MSALL shotgun lipidomics to determine the molecular signatures of exercise-induced adaptations to subcutaneous WAT (scWAT and BAT. Three weeks of exercise training decrease specific molecular species of phosphatidic acid (PA, phosphatidylcholines (PC, phosphatidylethanolamines (PE, and phosphatidylserines (PS in scWAT and increase specific molecular species of PC and PE in BAT. Exercise also decreases most triacylglycerols (TAGs in scWAT and BAT. In summary, exercise-induced changes to the scWAT and BAT lipidome are highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflect selective remodeling in scWAT and BAT of both phospholipids and glycerol lipids in response to exercise training, thus providing a comprehensive resource for future studies of lipid metabolism pathways.

Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder

NARCIS (Netherlands)

Ruhé, Henricus G.; Ooteman, Wendy; Booij, Jan; Michel, Martin C.; Moeton, Martina; Baas, Frank; Schene, Aart H.

2009-01-01

BACKGROUND: In major depressive disorder, selective serotonin reuptake inhibitors target the serotonin transporter (SERT). Their response rates (30-50%) are modified by SERT promotor polymorphisms (5-HTTLPR). OBJECTIVES: To quantify the relationship between SERT occupancy and response, and whether

Growth condition dependency is the major cause of non-responsiveness upon genetic perturbation.

Directory of Open Access Journals (Sweden)

Saman Amini

Full Text Available Investigating the role and interplay between individual proteins in biological processes is often performed by assessing the functional consequences of gene inactivation or removal. Depending on the sensitivity of the assay used for determining phenotype, between 66% (growth and 53% (gene expression of Saccharomyces cerevisiae gene deletion strains show no defect when analyzed under a single condition. Although it is well known that this non-responsive behavior is caused by different types of redundancy mechanisms or by growth condition/cell type dependency, it is not known what the relative contribution of these different causes is. Understanding the underlying causes of and their relative contribution to non-responsive behavior upon genetic perturbation is extremely important for designing efficient strategies aimed at elucidating gene function and unraveling complex cellular systems. Here, we provide a systematic classification of the underlying causes of and their relative contribution to non-responsive behavior upon gene deletion. The overall contribution of redundancy to non-responsive behavior is estimated at 29%, of which approximately 17% is due to homology-based redundancy and 12% is due to pathway-based redundancy. The major determinant of non-responsiveness is condition dependency (71%. For approximately 14% of protein complexes, just-in-time assembly can be put forward as a potential mechanistic explanation for how proteins can be regulated in a condition dependent manner. Taken together, the results underscore the large contribution of growth condition requirement to non-responsive behavior, which needs to be taken into account for strategies aimed at determining gene function. The classification provided here, can also be further harnessed in systematic analyses of complex cellular systems.

Molecular ecological network analyses.

Science.gov (United States)

Deng, Ye; Jiang, Yi-Huei; Yang, Yunfeng; He, Zhili; Luo, Feng; Zhou, Jizhong

2012-05-30

Understanding the interaction among different species within a community and their responses to environmental changes is a central goal in ecology. However, defining the network structure in a microbial community is very challenging due to their extremely high diversity and as-yet uncultivated status. Although recent advance of metagenomic technologies, such as high throughout sequencing and functional gene arrays, provide revolutionary tools for analyzing microbial community structure, it is still difficult to examine network interactions in a microbial community based on high-throughput metagenomics data. Here, we describe a novel mathematical and bioinformatics framework to construct ecological association networks named molecular ecological networks (MENs) through Random Matrix Theory (RMT)-based methods. Compared to other network construction methods, this approach is remarkable in that the network is automatically defined and robust to noise, thus providing excellent solutions to several common issues associated with high-throughput metagenomics data. We applied it to determine the network structure of microbial communities subjected to long-term experimental warming based on pyrosequencing data of 16 S rRNA genes. We showed that the constructed MENs under both warming and unwarming conditions exhibited topological features of scale free, small world and modularity, which were consistent with previously described molecular ecological networks. Eigengene analysis indicated that the eigengenes represented the module profiles relatively well. In consistency with many other studies, several major environmental traits including temperature and soil pH were found to be important in determining network interactions in the microbial communities examined. To facilitate its application by the scientific community, all these methods and statistical tools have been integrated into a comprehensive Molecular Ecological Network Analysis Pipeline (MENAP), which is open

A pH-responsive molecular switch with tricolor luminescence.

Science.gov (United States)

Ahn, Hyungmin; Hong, Jaewan; Kim, Sung Yeon; Choi, Ilyoung; Park, Moon Jeong

2015-01-14

We developed a new ratiometric pH sensor based on poly(N-phenylmaleimide) (PPMI)-containing block copolymer that emits three different fluorescent colors depending on the pH. The strong solvatochromism and tautomerism of the PPMI derivatives enabled precise pH sensing for almost the entire range of the pH scale. Theoretical calculations have predicted largely dissimilar band gaps for the keto, enol, and enolate tautomers of PPMI owing to low-dimensional conjugation effects. The tunable emission wavelength and intensity of our sensors, as well as the reversible color switching with high-luminescent contrast, were achieved using rational molecular design of PPMI analogues as an innovative platform for accurate H(+) detection. The self-assembly of block copolymers on the nanometer length scale was particularly highlighted as a novel prospective means of regulating fluorescence properties while avoiding the self-quenching phenomenon, and this system can be used as a fast responsive pH sensor in versatile device forms.

Development of a marine fish model for studying in vivo molecular responses in ecotoxicology

International Nuclear Information System (INIS)

Kong, R.Y.C.; Giesy, J.P.; Wu, R.S.S.; Chen, E.X.H.; Chiang, M.W.L.; Lim, P.L.; Yuen, B.B.H.; Yip, B.W.P.; Mok, H.O.L.; Au, D.W.T.

2008-01-01

A protocol for fixation and processing of whole adult marine medaka (Oryzias melastigma) was developed in parallel with in situ hybridization (ISH) and immunohistochemistry (IHC) for molecular analysis of in vivo gene and protein responses in fish. Over 200 serial sagittal sections (5 μm) can be produced from a single adult medaka to facilitate simultaneous localization and quantification of gene-specific mRNAs and proteins in different tissues and subcellular compartments of a single fish. Stereological analysis (as measured by volume density, V v ) was used to quantify ISH and IHC signals on tissue sections. Using the telomerase reverse transcriptase (omTERT) gene, omTERT and proliferating cell nuclear antigen (PCNA) proteins as examples, we demonstrated that it is possible to localize, quantify and correlate their tissue expression profiles in a whole fish system. Using chronic hypoxia (1.8 ± 0.2 mg O 2 L -1 for 3 months) as an environmental stressor, we were able to identify significant alterations in levels of omTERT mRNA, omTERT protein, PCNA (cell proliferation marker) and TUNEL (apoptosis) in livers of hypoxic O. melastigma (p < 0.05). Overall, the results suggest that O. melastigma can serve as a model marine fish for assessing multiple in vivo molecular responses to stresses in the marine environment

Metal nanostructures for the enhancement of the Raman response of molecular adsorbates

Science.gov (United States)

Giorgetti, Emilia; Giammanco, Francesco; Margheri, Giancarlo; Trigari, Silvana; Muniz-Miranda, Maurizio

2011-08-01

Spectroscopic investigation of metallic nanostructures of different size and morphology is presented, with particular focus on the capability of enhancing the Raman response of molecular adsorbates, namely on their SERS properties. In this framework, we describe recent results obtained with Au/Ag nanocages and Au nanostars, which can be used conveniently to shift the extinction spectra and the SERS activity up to the near infrared. In the case of nanostars, we present a synthesis procedure which permits fine tuning of their morphology and extinction, thus allowing preparation of structures with controlled SERS activity from 500 up to 1500 nm.

Early Complete Molecular Response to First-Line Nilotinib in Two Patients with Chronic Myeloid Leukemia Carrying the p230 Transcript

Directory of Open Access Journals (Sweden)

Marianna Greco

2013-01-01

Full Text Available Chronic myeloid leukemia (CML with the rare fusion gene e19a2, encoding a p230 protein, has been described in patients with typical or rather aggressive clinical course. Although tyrosine kinase inhibitors (TKIs induce a substantial cytogenetic and molecular response in all phases of CML, a minority of p230 positive patients have been treated with TKIs. We report two cases of CML patients carrying the p230 transcript, who achieved fast and deep complete molecular response (CMR after frontline treatment with nilotinib. Our results suggest the use of nilotinib as frontline agent for the treatment of this CML variant.

Heterogeneity of mammary lesions represent molecular differences

International Nuclear Information System (INIS)

Namba, Ruria; Gregg, Jeffrey P; Maglione, Jeannie E; Davis, Ryan R; Baron, Colin A; Liu, Stephenie; Carmack, Condie E; Young, Lawrence JT; Borowsky, Alexander D; Cardiff, Robert D

2006-01-01

Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies. We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution. We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes

Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

International Nuclear Information System (INIS)

Takaji Ikushima

1997-01-01

The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

2011-01-01

This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus.

Science.gov (United States)

Carr, Jillian M; Ashander, Liam M; Calvert, Julie K; Ma, Yuefang; Aloia, Amanda; Bracho, Gustavo G; Chee, Soon-Phaik; Appukuttan, Binoy; Smith, Justine R

2017-01-01

Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin- β 1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus

Directory of Open Access Journals (Sweden)

Jillian M. Carr

2017-01-01

Full Text Available Recent clinical reports indicate that infection with dengue virus (DENV commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells. Human retinal cells were inoculated with DENV-2 and monitored for up to 72 hours. Epithelial and endothelial cells supported DENV replication and release, but epithelial cells alone demonstrated clear cytopathic effect, and infection was more productive in those cells. Infection induced type I interferon responses from both cells, but this was stronger in epithelial cells. Endothelial cells increased expression of adhesion molecules, with sustained overexpression of vascular adhesion molecule-1. Transcellular impedance decreased for epithelial monolayers, but not endothelial monolayers, coinciding with cytopathic effect. This reduction was accompanied by disorganization of intracellular filamentous-actin and decreased expression of junctional molecules, zonula occludens 1, and catenin-β1. Changes in endothelial expression of adhesion molecules are consistent with the retinal vasculopathy seen in patients infected with DENV; decreases in epithelial junctional protein expression, paralleling loss of integrity of the epithelium, provide a molecular basis for DENV-associated macular edema. These molecular processes present potential therapeutic targets for vision-threatening dengue retinopathy.

An International Comparison of the Instigation and Design of Health Registers in the Epidemiological Response to Major Environmental Health Incidents.

Science.gov (United States)

Behbod, Behrooz; Leonardi, Giovanni; Motreff, Yvon; Beck, Charles R; Yzermans, Joris; Lebret, Erik; Muravov, Oleg I; Bayleyegn, Tesfaye; Wolkin, Amy Funk; Lauriola, Paolo; Close, Rebecca; Crabbe, Helen; Pirard, Philippe

Epidemiological preparedness is vital in providing relevant, transparent, and timely intelligence for the management, mitigation, and prevention of public health impacts following major environmental health incidents. A register is a set of records containing systematically collected, standardized data about individual people. Planning for a register of people affected by or exposed to an incident is one of the evolving tools in the public health preparedness and response arsenal. We compared and contrasted the instigation and design of health registers in the epidemiological response to major environmental health incidents in England, France, Italy, the Netherlands, and the United States. Consultation with experts from the 5 nations, supplemented with a review of gray and peer-reviewed scientific literature to identify examples where registers have been used. Populations affected by or at risk from major environmental health incidents in England, France, Italy, the Netherlands, and the United States. Nations were compared with respect to the (1) types of major incidents in their remit for considering a register; (2) arrangements for triggering a register; (3) approaches to design of register; (4) arrangements for register implementation; (5) uses of registers; and (6) examples of follow-up studies. Health registers have played a key role in the effective public health response to major environmental incidents, including sudden chemical, biological, radiological, or nuclear, as well as natural, more prolonged incidents. Value has been demonstrated in the early and rapid deployment of health registers, enabling the capture of a representative population. The decision to establish a health register must ideally be confirmed immediately or soon after the incident using a set of agreed criteria. The establishment of protocols for the instigation, design, and implementation of health registers is recommended as part of preparedness activities. Key stakeholders must be

Do Biology Majors Really Differ from Non–STEM Majors?

Science.gov (United States)

Cotner, Sehoya; Thompson, Seth; Wright, Robin

2017-01-01

Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students—including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences—if any exist—between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non–STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non–STEM majors are not unilaterally science averse; non–STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non–STEM majors are less likely than biology majors to see science as personally relevant; and non–STEM majors populations are likely to be more diverse—with respect to incoming knowledge, perceptions, backgrounds, and skills—than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. PMID:28798210

Molecular bases of methamphetamine-induced neurodegeneration.

Science.gov (United States)

Cadet, Jean Lud; Krasnova, Irina N

2009-01-01

Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. The addiction to METH is a major public concern because its chronic abuse is associated with serious health complications including deficits in attention, memory, and executive functions in humans. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. Thus, the purpose of the present paper is to review cellular and molecular mechanisms that might be responsible for METH neurotoxicity. These include oxidative stress, activation of transcription factors, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation, and various apoptotic pathways. Several approaches that allow protection against METH-induced neurotoxic effects are also discussed. Better understanding of the cellular and molecular mechanisms involved in METH toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of psychostimulant use disorders in humans.

Interactive effects of nutrition, reproductive state and pollution on molecular stress responses of mussels, Mytilus galloprovincialis Lamarck, 1819.

Science.gov (United States)

González-Fernández, Carmen; Albentosa, Marina; Sokolova, Inna

2017-10-01

Marine bivalves including mussels Mytilus galloprovincialis are commonly used as sentinels for pollution monitoring and ecosystem health assessment in the coastal zones. Use of biomarkers to assess the pollution effects assumes that the effects of pollutants on the biomarkers exceed the natural background variability; yet this assumption has rarely been tested. We exposed mussels at different reproductive stages and nutritive states to two concentrations of a polycyclic aromatic hydrocarbon (fluoranthene, 3 and 60 μg L -1 ) for three weeks. Expression levels of the molecular biomarkers related to the detoxification and general stress response [cytochrome P450 oxidase (CYP450), glutathione S-transferases (GST-α; GST-S1; GST-S2), the multixenobiotic resistance protein P-glycoprotein (PgP), metallothioneins (MT10 and MT20), heat shock proteins (HSP22, HSP70-2; HSP70-3; HSP70-4), as well as mRNA expression of two reproduction-related genes, vitellogenin (Vitel) and vitelline coat lysin M7 (VCLM7)] were measured. The mussels' nutrition and reproductive state affected the baseline mRNA levels of molecular biomarkers and modulated the transcriptional responses of biomarker genes to the pollutant exposure. Thus, mussel physiological state could act as a confounding factor in the evaluation of the response of pollution through molecular biomarkers. The biomarker baseline levels must be determined across a range of physiological states to enable the use of biomarkers in monitoring programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective excitation, relaxation, and energy channeling in molecular systems

International Nuclear Information System (INIS)

Rhodes, W.C.

1993-08-01

Research involves theoretical studies of response, relaxation, and correlated motion in time-dependent behavior of large molecular systems ranging from polyatomic molecules to protein molecules in their natural environment. Underlying theme is subsystem modulation dynamics. Main idea is that quantum mechanical correlations between components of a system develop with time, playing a major role in determining the balance between coherent and dissipative forces. Central theme is interplay of coherence and dissipation in determining the nature of dynamic structuring and energy flow in molecular transformation mechanisms. Subsystem equations of motion are being developed to show how nonlinear, dissipative dynamics of a particular subsystem arise from correlated interactions with the rest of the system (substituent groups, solvent, lattice modes, etc.); one consequence is resonance structures and networks. Quantum dynamics and thermodynamics are being applied to understand control and energy transfer mechanisms in biological functions of protein molecules; these mechanisms are both global and local. Besides the above theory, the research deals with phenomenological aspects of molecular systems

Clinical Efficacy and Safety of First-Line Dasatinib Therapy and the Relevance of Velocity of BCR-ABL1 Transcript Decline for Achievement of Molecular Responses in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Report from the Juntendo Yamanashi Cooperative Study Group.

Science.gov (United States)

Takaku, Tomoiku; Iriyama, Noriyoshi; Mitsumori, Toru; Sato, Eriko; Gotoh, Akihiko; Kirito, Keita; Noguchi, Masaaki; Koike, Michiaki; Sakamoto, Junichi; Oba, Koji; Komatsu, Norio

2018-01-01

The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy. © 2017 S. Karger AG, Basel.

Molecular responses in root-associative rhizospheric bacteria to variations in plant exudates

Science.gov (United States)

Abdoun, Hamid; McMillan, Mary; Pereg, Lily

2015-04-01

Plant exudates are a major factor in the interface of plant-soil-microbe interactions and it is well documented that the microbial community structure in the rhizosphere is largely influenced by the particular exudates excreted by various plants. Azospirillum brasilense is a plant growth promoting rhizobacterium that is known to interact with a large number of plants, including important food crops. The regulatory gene flcA has an important role in this interaction as it controls morphological differentiation of the bacterium that is essential for attachment to root surfaces. Being a response regulatory gene, flcA mediates the response of the bacterial cell to signals from the surrounding rhizosphere. This makes this regulatory gene a good candidate for analysis of the response of bacteria to rhizospheric alterations, in this case, variations in root exudates. We will report on our studies on the response of Azospirillum, an ecologically, scientifically and agriculturally important bacterial genus, to variations in the rhizosphere.

Molecular subtyping of cancer: current status and moving toward clinical applications.

Science.gov (United States)

Zhao, Lan; Lee, Victor H F; Ng, Michael K; Yan, Hong; Bijlsma, Maarten F

2018-04-12

Cancer is a collection of genetic diseases, with large phenotypic differences and genetic heterogeneity between different types of cancers and even within the same cancer type. Recent advances in genome-wide profiling provide an opportunity to investigate global molecular changes during the development and progression of cancer. Meanwhile, numerous statistical and machine learning algorithms have been designed for the processing and interpretation of high-throughput molecular data. Molecular subtyping studies have allowed the allocation of cancer into homogeneous groups that are considered to harbor similar molecular and clinical characteristics. Furthermore, this has helped researchers to identify both actionable targets for drug design as well as biomarkers for response prediction. In this review, we introduce five frequently applied techniques for generating molecular data, which are microarray, RNA sequencing, quantitative polymerase chain reaction, NanoString and tissue microarray. Commonly used molecular data for cancer subtyping and clinical applications are discussed. Next, we summarize a workflow for molecular subtyping of cancer, including data preprocessing, cluster analysis, supervised classification and subtype characterizations. Finally, we identify and describe four major challenges in the molecular subtyping of cancer that may preclude clinical implementation. We suggest that standardized methods should be established to help identify intrinsic subgroup signatures and build robust classifiers that pave the way toward stratified treatment of cancer patients.

Clinical trials using IFN-α as a vaccine adjuvant: new strategies for the molecular monitoring of the immune response

International Nuclear Information System (INIS)

Belardelli, F.; Arico, E.; Marincola, F.; Wang, E.

2009-01-01

The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients

The inflammatory response plays a major role in the acute radiation syndrome induced by fission radiation

International Nuclear Information System (INIS)

Agay, D.; Chancerelle, Y.; Hirodin, F.; Mathieu, J.; Multon, E.; Van Uye, A.; Mestries, J.C.

1997-01-01

At high dose rates, both gamma and neutron irradiation induce an acute inflammatory syndrome with huge intercellular communication disorders. This inflammatory syndrome evolves in two phases, separated by a latency phase. During the prodromal phase, the molecular and cellular lesions induced by free radicals trigger an initial response which associates cellular repair and multicellular interactions involving both humoral and nervous communications. A large part of perturbations constitute a non specific inflammatory syndrome and clinically silent coagulation disorders which are linked by common intercellular mediators. All these perturbations are rapidly reversible and there is no correlation between the radiation dose and the severity of the response. During the manifest-illness phase, both inflammatory and coagulation disorders resume, slightly preceding the clinical symptoms. Biochemical symptoms are moderate in the animals which will survive, but they escape regulatory mechanisms in those which will die, giving rise to a vicious circle. These biochemical disorders are largely responsible for the death. With lower dose rates, it cannot be excluded that great cellular communication disorders take place at the tissue level, with limited blood modifications. This aspect should be taken into account for the optimization of cytokine therapies. (authors)

[The molecular biology of epithelial ovarian cancer].

Science.gov (United States)

Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

2012-12-01

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

Sex specific molecular responses of quick-to-court protein in Indian malarial vector Anopheles culicifacies: conflict of mating versus blood feeding behaviour

Directory of Open Access Journals (Sweden)

Tanwee Das De

2017-07-01

Full Text Available Understanding the molecular basis of mosquito behavioural complexity plays a central role in designing novel molecular tools to fight against their vector-borne diseases. Although the olfactory system plays an important role in guiding and managing many behavioural responses including feeding and mating, but the sex-specific regulation of olfactory responses remain poorly investigated. From our ongoing transcriptomic data annotation of olfactory tissue of blood fed adult female An. culicifacies mosquitoes; we have identified a 383 bp long unique transcript encoding a Drosophila homolog of the quick-to-court protein. Previously this was shown to regulate courtship behaviour in adult male Drosophila. A comprehensive in silico analysis of the quick-to-court (qtc gene of An. culicifacies (Ac-qtc predicts a 1536 bp single copy gene encoding 511 amino acid protein, having a high degree of conservation with other insect homologs. The age-dependent increased expression of putative Ac-qtc correlated with the maturation of the olfactory system, necessary to meet the sex-specific conflicting demand of mating (mate finding versus host-seeking behavioural responses. Sixteen to eighteen hours of starvation did not alter Ac-qtc expression in both sexes, however, blood feeding significantly modulated its response in the adult female mosquitoes, confirming that it may not be involved in sugar feeding associated behavioural regulation. Finally, a dual behavioural and molecular assay indicated that natural dysregulation of Ac-qtc in the late evening might promote the mating events for successful insemination. We hypothesize that Ac-qtc may play a unique role to regulate the sex-specific conflicting demand of mosquito courtship behaviour versus blood feeding behaviour in the adult female mosquitoes. Further elucidation of this molecular mechanism may provide further information to evaluate Ac-qtc as a key molecular target for mosquito-borne disease management.

Global temperature response to the major volcanic eruptions in multiple reanalysis data sets

Directory of Open Access Journals (Sweden)

M. Fujiwara

2015-12-01

Full Text Available The global temperature responses to the eruptions of Mount Agung in 1963, El Chichón in 1982, and Mount Pinatubo in 1991 are investigated using nine currently available reanalysis data sets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR. Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979–2009 (for eight reanalysis data sets and 1958–2001 (for four reanalysis data sets, by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately, and common and different responses among the older and newer reanalysis data sets are highlighted for each eruption. In response to the Mount Pinatubo eruption, most reanalysis data sets show strong warming signals (up to 2–3 K for 1-year average in the tropical lower stratosphere and weak cooling signals (down to −1 K in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. Comparison of the results from several different reanalysis data sets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis data sets. The consistencies and differences among different reanalysis data sets provide a measure of the confidence and uncertainty in our current understanding of the volcanic response. The results of this intercomparison study may be useful for validation of climate model responses to volcanic forcing and for assessing proposed

Molecular events basic to cellular radiation response

International Nuclear Information System (INIS)

Kolodny, G.M.

The initiation and control of the division process in normal cells is studied to gain insight into changes in these regards caused by x-irradiation and neoplasia. The Primer Hypothesis for eukaryotic gene regulation proposes that small molecular weight RNA acts as primer for new RNA synthesis by hybridizing with DNA and there initiating the transcription of a new RNA chain. The experiments reported here indicate that small molecular weight RNA will induce the production of new proteins. These results are consistent with the Primer Hypothesis, and demonstrate that RNA can be taken up from the media by cells in culture and can induce in vitro the production of differentiated cell products

Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase I

Energy Technology Data Exchange (ETDEWEB)

Ariza, Antonio; Vickers, Tim J.; Greig, Neil; Fairlamb, Alan H.; Bond, Charles S., E-mail: c.s.bond@dundee.ac.uk [Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dundee DD1 5EH,Scotland (United Kingdom)

2005-08-01

The detoxification enzyme glyoxalase I from L. major has been crystallized. Preliminary molecular-replacement calculations indicate the presence of three glyoxalase I dimers in the asymmetric unit. Glyoxalase I (GLO1) is a putative drug target for trypanosomatids, which are pathogenic protozoa that include the causative agents of leishmaniasis. Significant sequence and functional differences between Leishmania major and human GLO1 suggest that it may make a suitable template for rational inhibitor design. L. major GLO1 was crystallized in two forms: the first is extremely disordered and does not diffract, while the second, an orthorhombic form, produces diffraction to 2.0 Å. Molecular-replacement calculations indicate that there are three GLO1 dimers in the asymmetric unit, which take up a helical arrangement with their molecular dyads arranged approximately perpendicular to the c axis. Further analysis of these data are under way.

Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

Science.gov (United States)

Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

2011-01-01

The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

Science.gov (United States)

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

International Nuclear Information System (INIS)

Lowe, Xiu R.; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

2008-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p -53 ) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease

Plasma fibronectin in patients undergoing major surgery

International Nuclear Information System (INIS)

Sallam, M.H.M.

2003-01-01

Plasma fibronectin in patients undergoing major surgery had been determined before and after operation. The study was done on 15 patients and 15 normal healthy individuals. The study revealed that patients subjected to major operation, their fibronectin level was normal before operation followed by reduction one day post-operation. After one week, fibronectin level raised again nearly to the pre-operations levels. The probable mechanisms of fibronectin in healing processes were discussed. Fibronectin (FN) is a family of structurally and immunologically related high molecular weight glycoproteins that are present in many cell surfaces, in extracellular fluids, in connective tissues and in most membranes. Interaction with certain discrete extracellular substances, such as a glucosaminoglycans (e.g. heparin), fibrin and collagen and with cell surface structure seem to account for many of its biological activities, among which are regulation of adhesion, spreading and locomotion (Mosesson and amrani, 1980). The concentration of Fn in human plasma decreases after extensive destruction such as that occurs in major surgery, burns or other trauma. This decrease has been generally though to be due to increased consumption of soluble plasma Fn in opsonization of particulate and soluble debris from circulation by the reticuloendothelial (RE) system. Fn rapidly appears in injury areas, in experimentally induced blisters, wounded and epithelium tissues (Petersen et al., 1985). Fn accumulates at times of increased vascular permeability and it is produced by cell of blood vessels in response to injury

Molecular identification of Cryptosporidium spp. in seagulls, pigeons, dogs, and cats in Thailand

OpenAIRE

Koompapong Khuanchai; Mori Hirotake; Thammasonthijarern Nipa; Prasertbun Rapeepun; Pintong Ai-rada; Popruk Supaluk; Rojekittikhun Wichit; Chaisiri Kittipong; Sukthana Yaowalark; Mahittikorn Aongart

2014-01-01

Zoonotic Cryptosporidium spp., particularly C. meleagridis, C. canis, and C. felis, are enteric protozoa responsible for major public health concerns around the world. To determine the spread of this parasite in Thailand, we conducted molecular identification of Cryptosporidium spp. from animal samples around the country, by collecting and investigating the feces of seagulls (Chroicocephalus brunnicephalus and Chroicocephalus ridibundus), domestic pigeons (Columba livia domestica), dogs, and ...

Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.

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Iris J Gonzalez-Leal

2014-09-01

Full Text Available Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb and L (Ctsl play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrophages play during Leishmania infection, we generated bone-marrow derived dendritic cells (BMDC and macrophages (BMM from Ctsb-/- and Ctsl-/- mice, and studied the effects of Ctsb and Ctsl deficiency on the survival of L. major in infected cells. Furthermore, the signals used by dendritic cells to instruct Th cell polarization were addressed: the expression of MHC class II and co-stimulatory molecules, and cytokine production. We found that Ctsb-/- BMDC express higher levels of MHC class II molecules than wild-type (WT and Ctsl-/- BMDC, while there were no significant differences in the expression of co-stimulatory molecules between cathepsin-deficient and WT cells. Moreover, both BMDC and BMM from Ctsb-/- mice significantly up-regulated the levels of interleukin 12 (IL-12 expression, a key Th1-inducing cytokine. These findings indicate that Ctsb-/- BMDC display more pro-Th1 properties than their WT and Ctsl-/- counterparts, and therefore suggest that Ctsb down-regulates the Th1 response to L. major. Moreover, they propose a novel role for Ctsb as a regulator of cytokine expression.

Molecular events by which dendritic cells promote Th2 immune protection in helmith infection.

Science.gov (United States)

Méndez-Samperio, Patricia

2016-10-01

Helminth parasites are a major cause of global infectious diseases, affecting nearly one quarter of the world's population. The common feature of helminth infections is to skew the immune system towards a T-helper 2 (Th2) response that helps to control disease. Dendritic cells (DCs), which are professional antigen-presenting cells, play a critical role for Th2 skewing against helminth parasites. However, the molecular mechanisms by which helminth antigens activate DCs for Th2 polarization have not yet been clearly defined. This review provides a focused update on the major role of DCs for inducing and/or enhancing Th2 immune responses in helminthic infection and will discuss the main signalling-dependent and independent mechanisms by which helminth antigens activate DCs for Th2 skewing.

Physiological and molecular responses of the earthworm (Eisenia fetida) to soil chlortetracycline contamination

International Nuclear Information System (INIS)

Lin Dasong; Zhou Qixing; Xu Yingming; Chen Chun; Li Ye

2012-01-01

This study aims to evaluate toxic effects of exposure to chlortetracycline (CTC) in soil on reproductive endpoints (juvenile counts and cocoon counts), biochemical responses, and genotoxic potentials of the earthworm Eisenia fetida. Results showed that juvenile counts and cocoon counts of the tested earthworms were reduced after exposure to CTC. The effective concentrations (EC 50 values) for juvenile and cocoon counts were 96.1 and 120.3 mg/kg, respectively. Treatment of earthworms with CTC significantly changed the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST). An increase in malondialdehyde (MDA) indicated that CTC could cause cellular lipid peroxidation in the tested earthworms. The percentage of DNA in the tail of single-cell gel electrophoresis of coelomocytes as an indication of DNA damage increased after treatment with different doses of CTC, and a dose-dependent DNA damage of coelomocytes was found. In conclusion, CTC induces physiological responses and genotoxicity on earthworms. - Highlights: ► Reproductive endpoints were assessed for Eisenia fetida exposed to chlortectracyline (CTC). ► CTC may induce physiological and molecular responses in E. fetida. ► A clear relationship was observed between CTC doses and DNA damage of coelomocytes. - Chlortetracycline in soil could induce physiological responses and genotoxicity on earthworms at realistic environmental concentrations.

Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials [version 1; referees: 2 approved

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Frank Lieberman

2017-10-01

Full Text Available This is an exciting time in neuro-oncology. Discoveries elucidating the molecular mechanisms of oncogenesis and the molecular subtypes of glioblastoma multiforme (GBM have led to new diagnostic and classification schemes with more prognostic power than histology alone. Molecular profiling has become part of the standard neuropathological evaluation of GBM. Chemoradiation followed by adjuvant temozolomide remains the standard therapy for newly diagnosed GBM, but survival remains unsatisfactory. Patients with recurrent GBM continue to have a dismal prognosis, but neuro-oncology centers with active clinical trial programs are seeing a small but increasing cadre of patients with longer survival. Molecularly targeted therapeutics, personalized therapy based on molecular profiling of individual tumors, and immunotherapeutic strategies are all being evaluated and refined in clinical trials. Understanding of the molecular mechanisms of tumor-mediated immunosuppression, and specifically interactions between tumor cells and immune effector cells in the tumor microenvironment, has led to a new generation of immunotherapies, including vaccine and immunomodulatory strategies as well as T-cell-based treatments. Molecularly targeted therapies, chemoradiation, immunotherapies, and anti-angiogenic therapies have created the need to develop more reliable neuroimaging criteria for differentiating the effects of therapy from tumor progression and changes in blood–brain barrier physiology from treatment response. Translational clinical trials for patients with GBM now incorporate quantitative imaging using both magnetic resonance imaging and positron emission tomography techniques. This update presents a summary of the current standards for therapy for newly diagnosed and recurrent GBM and highlights promising translational research.

Tactical and operational response to major incidents: feasibility and reliability of skills assessment using novel virtual environments.

Science.gov (United States)

Cohen, Daniel; Sevdalis, Nick; Patel, Vishal; Taylor, Michael; Lee, Henry; Vokes, Mick; Heys, Mick; Taylor, David; Batrick, Nicola; Darzi, Ara

2013-07-01

To determine feasibility and reliability of skills assessment in a multi-agency, triple-site major incident response exercise carried out in a virtual world environment. Skills assessment was carried out across three scenarios. The pre-hospital scenario required paramedics to triage and treat casualties at the site of an explosion. Technical skills assessment forms were developed using training syllabus competencies and national guidelines identified by pre-hospital response experts. Non-technical skills were assessed using a seven-point scale previously developed for use by pre-hospital paramedics. The two in-hospital scenarios, focusing on a trauma team leader and a silver/clinical major incident co-ordinator, utilised the validated Trauma-NOTECHS scale to assess five domains of performance. Technical competencies were assessed using an ATLS-style competency scale for the trauma scenario. For the silver scenario, the assessment document was developed using competencies described from a similar role description in a real-life hospital major incident plan. The technical and non-technical performance of all participants was assessed live by two experts in each of the three scenarios and inter-assessor reliability was computed. Participants also self-assessed their performance using identical proformas immediately after the scenarios were completed. Self and expert assessments were correlated (assessment cross-validation). Twenty-three participants underwent all scenarios and assessments. Performance assessments were feasible for both experts as well as the participants. Non-technical performance was generally scored higher than technical performance. Very good inter-rater reliability was obtained between expert raters across all scenarios and both technical and non-technical aspects of performance (reliability range 0.59-0.90, Psassessment in technical skills across all three scenarios (correlation range 0.52-0.84, Psskills. This study establishes feasibility and

Enhancement of immune response induced by DNA vaccine cocktail expressing complete LACK and TSA genes against Leishmania major.

Science.gov (United States)

Ghaffarifar, Fatemeh; Jorjani, Ogholniaz; Sharifi, Zohreh; Dalimi, Abdolhossein; Hassan, Zuhair M; Tabatabaie, Fatemeh; Khoshzaban, Fariba; Hezarjaribi, Hajar Ziaei

2013-04-01

Leishmaniasis is an important disease in humans. Leishmania homologue of receptor for Activated C Kinase (LACK) and thiol specific antioxidant (TSA) as immuno-dominant antigens of Leishmania major are considered the most promising molecules for a DNA vaccine. We constructed a DNA cocktail, containing plasmids encoding LACK and TSA genes of Leishmania major and evaluated the immune response and survival rate in BALB/c mice. IgG and Interferon gamma values were noticeably increased in the immunized group with DNA cocktail vaccine, which were significantly higher than those in the single-gene vaccinated and control groups (p 0.05). The immunized mice with the cocktail DNA vaccine presented a considerable reduction in diameter of lesion compared to other groups and a significant difference was observed (p < 0.05) in this regard. The survival time of the immunized mice with the cocktail DNA vaccine was significantly higher than that in the other groups (p < 0.05) after their being challenged with Leishmania major. The findings of this study indicated that the cocktail DNA vaccine increased the cellular response and survival rate and induced protection against infection with Leishmania in the mice. © 2012 The Authors © 2012 APMIS.

Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

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André Russowsky Brunoni

Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention

Molecular basis of IgE-recognition of Lol p 5, a major allergen of rye-grass pollen.

Science.gov (United States)

Suphioglu, C; Blaher, B; Rolland, J M; McCluskey, J; Schäppi, G; Kenrick, J; Singh, M B; Knox, R B

1998-04-01

Grass pollen, especially of rye-grass (Lolium perenne). represents an important cause of type I allergy. Identification of IgE-binding (allergenic) epitopes of major grass pollen allergens is essential for understanding the molecular basis of interaction between allergens and human IgE antibodies and therefore facilitates the devising of safer and more effective diagnostic and immunotherapy reagents. The aim of this study was to identify the allergenic epitopes of Lol p 5, a major allergen of rye-grass pollen, immunodissect these epitopes further so that the amino acid residues critical for antibody binding can be determined and investigate the conservation and nature of these epitopes within the context of the natural grass pollen allergens. Peptides, 12-13 amino acid residues long and overlapping each other by 4 amino acid residues, based on the entire deduced amino acid sequence of the coding region of Lol p 5, were synthesised and assayed for IgE-binding. Two strong IgE-binding epitopes (Lol p 5 (49-60) and (265-276), referred to as peptides 7 and 34, respectively) were identified. These epitopes were further resolved by truncated peptides and amino acid replacement studies and the amino acid residues critical for IgE-binding determined (Lol p 5 (49-60) residue Lys57 and (265-276) residue Lys275). Sequences of these epitopes were conserved in related allergens and may form the conserved allergenic domains responsible for the cross-reactivity observed between pollen allergens of taxonomically related grasses. Furthermore, due to its strong IgE-reactivity, synthetic peptide Lol p 5 (265-276) was used to affinity-purify specific IgE antibodies which recognised proteins of other clinically important grass pollens. further indicating presence of allergenic cross-reactivity at the level of allergenic epitope. Moreover, Lol p 5 (265 276) demonstrated a strong capacity to inhibit IgE-binding to natural rye-grass pollen proteins highlighting the antibody accessibility

Thermal-structural response of EBR-II major components under reactor operational transients

International Nuclear Information System (INIS)

Chang, L.K.; Lee, M.J.

1983-01-01

Until recently, the LMFBR safety research has been focused primarily on severe but highly unlikely accident, such as hypothetical-core-disruptive accidents (HCDA's), and not enough attention has been given to accident prevention, which is less severe but more likely sequence. The objective of the EBR-II operational reliability testing (ORT) is to demonstrate that the reactor can be designed and operated to prevent accident. A series of mild duty cycles and overpower transients were designed for accident prevention tests. An assessment of the EBR-II major plant components has been performed to assure structural integrity of the reactor plant for the ORT program. In this paper, the thermal-structural response and structural evaluation of the reactor vessel, the reactor-vessel cover, the intermediate heat exchanger (IHX) and the superheater are presented

Effects of social conditions during early development on stress response and personality traits in great tits (Parus major)

NARCIS (Netherlands)

Naguib, M.; Floercke, C.; Oers, van K.

2011-01-01

Environmental conditions during early development play a crucial role in shaping an organism's phenotype. To test how social group size affects stress response and behavioral characteristics, we used great tits (Parus major) from selection lines for exploratory behavior, a proxy for an avian

Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

NARCIS (Netherlands)

Ribeiro de Jesus, P.R.

2015-01-01

Biochemical, physiological and molecular responses of Ricinus communis seeds and seedlings to different temperatures: a multi-omics approach

by Paulo Roberto Ribeiro de Jesus

The main objective of this thesis was to provide a detailed

Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

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Richard A Rudick

Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.

Molecular-Scale Electronics: From Concept to Function.

Science.gov (United States)

Xiang, Dong; Wang, Xiaolong; Jia, Chuancheng; Lee, Takhee; Guo, Xuefeng

2016-04-13

Creating functional electrical circuits using individual or ensemble molecules, often termed as "molecular-scale electronics", not only meets the increasing technical demands of the miniaturization of traditional Si-based electronic devices, but also provides an ideal window of exploring the intrinsic properties of materials at the molecular level. This Review covers the major advances with the most general applicability and emphasizes new insights into the development of efficient platform methodologies for building reliable molecular electronic devices with desired functionalities through the combination of programmed bottom-up self-assembly and sophisticated top-down device fabrication. First, we summarize a number of different approaches of forming molecular-scale junctions and discuss various experimental techniques for examining these nanoscale circuits in details. We then give a full introduction of characterization techniques and theoretical simulations for molecular electronics. Third, we highlight the major contributions and new concepts of integrating molecular functionalities into electrical circuits. Finally, we provide a critical discussion of limitations and main challenges that still exist for the development of molecular electronics. These analyses should be valuable for deeply understanding charge transport through molecular junctions, the device fabrication process, and the roadmap for future practical molecular electronics.

Unraveling the Root Proteome Changes and Its Relationship to Molecular Mechanism Underlying Salt Stress Response in Radish (Raphanus sativus L.

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Xiaochuan Sun

2017-07-01

Full Text Available To understand the molecular mechanism underlying salt stress response in radish, iTRAQ-based proteomic analysis was conducted to investigate the differences in protein species abundance under different salt treatments. In total, 851, 706, and 685 differential abundance protein species (DAPS were identified between CK vs. Na100, CK vs. Na200, and Na100 vs. Na200, respectively. Functional annotation analysis revealed that salt stress elicited complex proteomic alterations in radish roots involved in carbohydrate and energy metabolism, protein metabolism, signal transduction, transcription regulation, stress and defense and transport. Additionally, the expression levels of nine genes encoding DAPS were further verified using RT-qPCR. The integrative analysis of transcriptomic and proteomic data in conjunction with miRNAs was further performed to strengthen the understanding of radish response to salinity. The genes responsible for signal transduction, ROS scavenging and transport activities as well as several key miRNAs including miR171, miR395, and miR398 played crucial roles in salt stress response in radish. Based on these findings, a schematic genetic regulatory network of salt stress response was proposed. This study provided valuable insights into the molecular mechanism underlying salt stress response in radish roots and would facilitate developing effective strategies toward genetically engineered salt-tolerant radish and other root vegetable crops.

Assessment of emergency response planning and implementation in the aftermath of major natural disasters and technological accidents

International Nuclear Information System (INIS)

Milligan, Patricia A.; Jones, Joseph; Walton, F.; Smith, J.D.

2008-01-01

Emergency planning around nuclear power plants represents some of the most mature and well developed emergency planning in the United States. Since the implementation of NUREG-0654 / FEMA-REP-1, Rev. 1, A Criteria for Preparation and Evaluation of Radiological Emergency Response Plans and Preparedness in Support of Nuclear Power Plants (NRC, 1980a) the licensees, local, and State agencies have developed detailed Radiological Emergency Response Programs. An important component of these plans is the evacuation of the population in the event of a general emergency condition at the plant. In January 2005, the U.S. Nuclear Regulatory Commission (NRC) published the landmark report, 'Identification and Analysis of Factors Affecting Emergency Evacuations' (NUREG/CR 6864/), which represented the most comprehensive investigation of public evacuations in the United States in more than 15 years. Since the completion of this research, several high profile evacuations have occurred, including Hurricane Katrina in New Orleans, Hurricane Rita in Houston, as well as major wildfires across the western U.S. The NRC commissioned an update to its 2005 evacuation case study publication to evaluate the evacuation experience of the selected communities (e.g., timeliness, related injuries, hazard avoidance); the level of preplanning that was in place for the affected areas and extent that the pre planned requirements were implemented during the emergency response; the critical factors contributing to the efficiency of or impediments to the evacuations (e.g., training, drills, preparedness, experience, resources, facilities, and organizational structure); and additional factors that may have contributed to less than satisfactory public response (i.e., availability of personal transportation, use of public transportation, lack of availability of shelters, etc.). The comprehensive report will be published in fall of 2008 as NUREG/CR-6981, Assessment of Emergency Response Planning and

Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

Science.gov (United States)

Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

2015-12-05

Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses.

Directory of Open Access Journals (Sweden)

Rafael Fonseca Benevenuto

Full Text Available Some genetically modified (GM plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses.

Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

Directory of Open Access Journals (Sweden)

Moritz Palmowski

2009-09-01

Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

Gender and Personality Differences in Response to Social Stressors in Great Tits (Parus major.

Directory of Open Access Journals (Sweden)

Esther van der Meer

Full Text Available In response to stressors, animals can increase the activity of the hypothalamic-pituitary-adrenocortical axis, resulting in elevated glucocorticoid concentrations. An increase in glucocorticoids results in an increase in heterophils and a decrease in lymphocytes, which ratio (H/L-ratio is an indicator of stress in birds. The physiological response to a stressor can depend on individual characteristics, like dominance rank, sex and personality. Although the isolated effects of these characteristics on the response to a stressor have been well studied, little is known about the response in relation to a combination of these characteristics. In this study we investigate the relationship between social stress, dominance rank, sex and exploratory behaviour as a validated operational measure of personality in great tits (Parus major. Great tits show consistent individual differences in behaviour and physiology in response to stressors, and exploratory behaviour can be classified as fast or slow exploring. We group-housed four birds, two fast and two slow explorers, of the same sex that were previously singly housed, in an aviary and compared the H/L-ratio, lymphocyte and heterophil count before and after group housing. After experiencing the social context all birds increased their H/L-ratio and heterophil count. Females showed a stronger increase in H/L-ratio and heterophil count than males, which seemed to be related to a higher number of agonistic interactions compared to males. Dominance rank and exploration type did not affect the H/L-ratio or heterophil count. Contrary to our expectations, all birds increased their lymphocyte count. However, this increase was slower for fast than for slow explorers. Our study suggests that personality and sex related differences, but not dominance rank, are associated with changes in an individual's physiological response due to a social context.

Identification of the major allergens of Indian scad (Decapterus russelli).

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Misnan, Rosmilah; Murad, Shahnaz; Jones, Meinir; Taylor, Graham; Rahman, Dinah; Arip, Masita; Abdullah, Noormalin; Mohamed, Jamaluddin

2008-12-01

The purpose of this study was to characterize major allergens of Indian scad (Decapterus russelli) which is among the most commonly consumed fish in Malaysia. Raw and cooked extracts of the fish were prepared. Protein profiles and IgE binding patterns were produced by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting using sera from subjects with fish allergy. The major allergens of the fish were then identified by two-dimensional electrophoresis (2-DE), followed by mass spectrometry of the peptide digests. The SDS-PAGE of the raw extract revealed 27 protein fractions over a wide molecular weight range, while the cooked extract demonstrated only six protein fractions. The 1-DE immunoblotting detected 14 IgE-binding proteins, with a molecular weight range from 90 to fish. The approximately 12 kDa band was a heat-resistant protein while the approximately 51 and 46 kDa proteins were sensitive to heat. The 2-DE gel profile of the raw extract demonstrated > 100 distinct protein spots and immunoblotting detected at least 10 different major IgE reactive spots with molecular masses as expected and isoelectric point (pI) values ranging from 4.0 to 7.0. A comparison of the major allergenic spot sequences of the 12 kDa proteins with known protein sequences in databases revealed extensive similarity with fish parvalbumin. In conclusion, this study demonstrated that a parvalbumin which is similar to Gad c 1 is the major allergen of Indian scad. Interestingly, we also detected heat-sensitive proteins as major allergenic components in our fish allergy patients.

A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

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Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

2016-08-10

Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

Molecular cloning and immunochemical characterization of a novel major Japanese cedar pollen allergen belonging to the aspartic protease family.

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Ibrahim, Ahmed Ragaa Nour; Kawamoto, Seiji; Aki, Tsunehiro; Shimada, Yayoi; Rikimaru, Satoshi; Onishi, Nobukazu; Babiker, Elfadil Elfadl; Oiso, Isao; Hashimoto, Kunihiko; Hayashi, Takaharu; Ono, Kazuhisa

2010-01-01

Japanese cedar (Cryptomeria japonica) pollen is a major cause of seasonal pollinosis in Japan. Protease activity in the pollen grains may trigger pro-allergic responses but no such proteases have yet been identified as pollen allergens. We report the molecular cloning and immunochemical characterization of a novel C. japonica pollen allergen belonging to the aspartic protease family. We focused on the C. japonica pollen allergen spot No. 63 (CPA63, 47.5% IgE binding frequency) on our 2-dimensional IgE immunoblot map. The internal amino acid sequences were determined using time-of-flight mass spectrometry. Full-length cpa63 cDNA was cloned by rapid amplification of cDNA ends (RACE)-PCR. Recombinant CPA63 (r-CPA63) was expressed using the baculovirus-insect cell culture system and its IgE binding capacity was analyzed by enzyme-linked immunosorbent assay (ELISA). The proteolytic activity of r-CPA63 was also assessed using a putative mature enzyme produced upon autolysis. cpa63 cDNA encoded a 472 amino acid polypeptide showing about 40% sequence identity to members of the plant atypical aspartic protease family. ELISA showed that r-CPA63 was recognized by IgE antibodies in the serum of 58% (18/31) of Japanese cedar pollinosis patients. We also demonstrated an aspartic protease-like enzyme activity of the putative mature r-CPA63. We have identified the first plant aspartic protease allergen from Japanese cedar pollen. The availability of the CPA63 sequence and its recombinant allergen production system are useful not only for pharmaceutical applications but also for further examination of the role of protease activity in the pathogenesis of cedar pollinosis. 2010 S. Karger AG, Basel.

The Relationship between 4-H Division Leaders' Propensity toward Delegation and Involvement in and Major Responsibility for Leader Identification and Selection.

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Dunbar, Mary Elizabeth

This research was to determine the relationship between New York State Cooperative Extension 4-H Division Leaders' propensity toward delegation of work responsibility and (1) their degree of involvement in the performance of leader identification and selection tasks, (2) assignment of major responsibility for these tasks, and (3) other selected…

Do Biology Majors Really Differ from Non-STEM Majors?

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Cotner, Sehoya; Thompson, Seth; Wright, Robin

2017-01-01

Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students-including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences-if any exist-between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non-STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non-STEM majors are not unilaterally science averse; non-STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non-STEM majors are less likely than biology majors to see science as personally relevant; and non-STEM majors populations are likely to be more diverse-with respect to incoming knowledge, perceptions, backgrounds, and skills-than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. © 2017 S. Cotner et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation

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Hurst, Jane L.; Beynon, Robert J.; Armstrong, Stuart D.; Davidson, Amanda J.; Roberts, Sarah A.; Gómez-Baena, Guadalupe; Smadja, Carole M.; Ganem, Guila

2017-01-01

When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal. PMID:28337988

Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

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Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

2015-01-01

Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder: neuroimaging approaches.

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Phillips, Mary L; Chase, Henry W; Sheline, Yvette I; Etkin, Amit; Almeida, Jorge R C; Deckersbach, Thilo; Trivedi, Madhukar H

2015-02-01

Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.

Evidence of major genes for plasma HDL, LDL cholesterol and triglyceride levels at baseline and in response to 20 weeks of endurance training: the HERITAGE Family Study.

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An, P; Borecki, I B; Rankinen, T; Després, J-P; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2005-01-01

This study assessed major gene effects for baseline HDL-C, LDL-C, TG, and their training responses (post-training minus baseline) in 527 individuals from 99 White families and 326 individuals from 113 Black families in the HERITAGE Family Study. The baseline phenotypes were adjusted for the effects of age and BMI, and the training response phenotypes were adjusted for the effects of age, BMI, and their respective baseline values, within each of the sex-by-generation-by-race groups, prior to genetic analyses. In Whites, we found that LDL-C at baseline and HDL-C training response were under influence of major recessive genes (accounting for 2--30 % of the variance) and multifactorial (polygenic and familial environmental) effects. Interactions of these major genes with sex, age, and BMI were tested, and found to be nonsignificant. In Blacks, we found that baseline HDL-C was influenced by a major dominant gene without a multifactorial component. This major gene effect accounted for 45 % of the variance, and exhibited no significant genotype-specific interactions with age, sex, and BMI. Evidence of major genes for the remaining phenotypes at baseline and in response to endurance training were not found in both races, though some were influenced by major effects that did not follow Mendelian expectations or were with ambiguous transmission from parents to offspring. In summary, major gene effects that influence baseline plasma HDL-C and LDL-C levels as well as changes in HDL-C levels in response to regular exercise were detected in the current study.

Interpersonal impacts mediate the association between personality and treatment response in major depression.

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Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

2016-07-01

Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Genome-wide transcription responses to synchrotron microbeam radiotherapy.

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Sprung, Carl N; Yang, Yuqing; Forrester, Helen B; Li, Jason; Zaitseva, Marina; Cann, Leonie; Restall, Tina; Anderson, Robin L; Crosbie, Jeffrey C; Rogers, Peter A W

2012-10-01

The majority of cancer patients achieve benefit from radiotherapy. A significant limitation of radiotherapy is its relatively low therapeutic index, defined as the maximum radiation dose that causes acceptable normal tissue damage to the minimum dose required to achieve tumor control. Recently, a new radiotherapy modality using synchrotron-generated X-ray microbeam radiotherapy has been demonstrated in animal models to ablate tumors with concurrent sparing of normal tissue. Very little work has been undertaken into the cellular and molecular mechanisms that differentiate microbeam radiotherapy from broad beam. The purpose of this study was to investigate and compare the whole genome transcriptional response of in vivo microbeam radiotherapy versus broad beam irradiated tumors. We hypothesized that gene expression changes after microbeam radiotherapy are different from those seen after broad beam. We found that in EMT6.5 tumors at 4-48 h postirradiation, microbeam radiotherapy differentially regulates a number of genes, including major histocompatibility complex (MHC) class II antigen gene family members, and other immunity-related genes including Ciita, Ifng, Cxcl1, Cxcl9, Indo and Ubd when compared to broad beam. Our findings demonstrate molecular differences in the tumor response to microbeam versus broad beam irradiation and these differences provide insight into the underlying mechanisms of microbeam radiotherapy and broad beam.

Emergency Response and the International Charter Space and Major Disasters

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Jones, B.; Lamb, R.

2011-12-01

Responding to catastrophic natural disasters requires information. When the flow of information on the ground is interrupted by crises such as earthquakes, landslides, volcanoes, hurricanes, and floods, satellite imagery and aerial photographs become invaluable tools in revealing post-disaster conditions and in aiding disaster response and recovery efforts. USGS is a global clearinghouse for remotely sensed disaster imagery. It is also a source of innovative products derived from satellite imagery that can provide unique overviews as well as important details about the impacts of disasters. Repeatedly, USGS and its resources have proven their worth in assisting with disaster recovery activities in the United States and abroad. USGS has a well-established role in emergency response in the United States. It works closely with the Federal Emergency Management Agency (FEMA) by providing first responders with satellite and aerial images of disaster-impacted sites and products developed from those images. The combination of the USGS image archive, coupled with its global data transfer capability and on-site science staff, was instrumental in the USGS becoming a participating agency in the International Charter Space and Major Disasters. This participation provides the USGS with access to international members and their space agencies, to information on European and other global member methodology in disaster response, and to data from satellites operated by Charter member countries. Such access enhances the USGS' ability to respond to global emergencies and to disasters that occur in the United States (US). As one example, the Charter agencies provided imagery to the US for over 4 months in response to the Gulf oil spill. The International Charter mission is to provide a unified system of space data acquisition and delivery to those affected by natural or man-made disasters. Each member space agency has committed resources to support the provisions of the Charter and

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

International Nuclear Information System (INIS)

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun; Yang, Chung S.; Zhang, Jinsong

2015-01-01

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at

Green tea polyphenol (−)-epigallocatechin-3-gallate triggered hepatotoxicity in mice: Responses of major antioxidant enzymes and the Nrf2 rescue pathway

Energy Technology Data Exchange (ETDEWEB)

Wang, Dongxu; Wang, Yijun; Wan, Xiaochun [Key Laboratory of Tea Biochemistry & Biotechnology, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui 230036 (China); Yang, Chung S. [Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 (United States); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [Key Laboratory of Tea Biochemistry & Biotechnology, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui 230036 (China)

2015-02-15

(−)-Epigallocatechin-3-gallate (EGCG), a constituent of green tea, has been suggested to have numerous health-promoting effects. On the other hand, high-dose EGCG is able to evoke hepatotoxicity. In the present study, we elucidated the responses of hepatic major antioxidant enzymes and nuclear factor erythroid 2-related factor 2 (Nrf2) rescue pathway to high-dose levels of EGCG in Kunming mice. At a non-lethal toxic dose (75 mg/kg, i.p.), repeated EGCG treatments markedly decreased the levels of superoxide dismutase, catalase, and glutathione peroxidase. As a rescue response, the nuclear distribution of Nrf2 was significantly increased; a battery of Nrf2-target genes, including heme oxygenase 1 (HO1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and those involved in glutathione and thioredoxin systems, were all up-regulated. At the maximum tolerated dose (45 mg/kg, i.p.), repeated EGCG treatments did not disturb the major antioxidant defense. Among the above-mentioned genes, only HO1, NQO1, and GST genes were significantly but modestly up-regulated, suggesting a comprehensive and extensive activation of Nrf2-target genes principally occurs at toxic levels of EGCG. At a lethal dose (200 mg/kg, i.p.), a single EGCG treatment dramatically decreased not only the major antioxidant defense but also the Nrf2-target genes, demonstrating that toxic levels of EGCG are able to cause a biphasic response of Nrf2. Overall, the mechanism of EGCG-triggered hepatotoxicity involves suppression of major antioxidant enzymes, and the Nrf2 rescue pathway plays a vital role for counteracting EGCG toxicity. - Highlights: • EGCG at maximum tolerated dose does not disturb hepatic major antioxidant defense. • EGCG at maximum tolerated dose modestly upregulates hepatic Nrf2 target genes. • EGCG at toxic dose suppresses hepatic major antioxidant enzymes. • EGCG at non-lethal toxic dose pronouncedly activates hepatic Nrf2 rescue response. • EGCG at

Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

Science.gov (United States)

Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

2013-08-01

Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

Hofmeister effect on thermo-responsive poly(propylene oxide): Role of polymer molecular weight and concentration.

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Moghaddam, Saeed Zajforoushan; Thormann, Esben

2016-03-01

Although a vast amount of research has been dedicated to investigate the Hofmeister effect on the stability of polymer solutions, a clear understanding of the role of polymer properties in this phenomenon is still missing. Here, the Hofmeister effect of NaCl (destabilizing) and NaSCN (stabilizing) salts on aqueous solutions of poly(propylene oxide) (PPO) is studied. Four different molecular weights of PPO were investigated, to determine how the variation in the polymer coil size affects the Hofmeister effect. The investigation was further conducted for different PPO concentrations, in order to understand the effect of inter-chain interactions on the response to addition of salt. The temperature-driven phase separation of the solutions was monitored by differential scanning calorimetry, which provides the precise value of the phase separation temperature, as well as the enthalpy change accompanied with the transition. It was observed that increasing the molecular weight weakens the effect of the both salts, which is interpreted in terms of a scaling law between the molecular weight and the accessible surface area of the polymers. Increasing the PPO concentration further diminished the NaCl effect, but amplified the NaSCN effect. This difference is attributed to an electrostatic stabilization mechanism in the case of NaSCN. Copyright © 2015 Elsevier Inc. All rights reserved.

Foundational Concepts and Underlying Theories for Majors in "Biochemistry and Molecular Biology"

Science.gov (United States)

Tansey, John T.; Baird, Teaster, Jr.; Cox, Michael M.; Fox, Kristin M.; Knight, Jennifer; Sears, Duane; Bell, Ellis

2013-01-01

Over the past two years, through an NSF RCN UBE grant, the ASBMB has held regional workshops for faculty members and science educators from around the country that focused on identifying: 1) core principles of biochemistry and molecular biology, 2) essential concepts and underlying theories from physics, chemistry, and mathematics, and 3)…

Pilot program: NRC severe reactor accident incident response training manual. Overview and summary of major points

International Nuclear Information System (INIS)

McKenna, T.J.; Martin, J.A. Jr.; Giitter, J.G.; Miller, C.W.; Hively, L.M.; Sharpe, R.W.; Watkins

1987-02-01

Overview and Summary of Major Points is the first in a series of volumes that collectively summarize the U.S. Nuclear Regulatory Commission (NRC) emergency response during severe power reactor accidents and provide necessary background information. This volume describes elementary perspectives on severe accidents and accident assessment. Other volumes in the series are: Volume 2-Severe Reactor Accident Overview; Volume 3- Response of Licensee and State and Local Officials; Volume 4-Public Protective Actions-Predetermined Criteria and Initial Actions; Volume 5 - U.S. Nuclear Regulatory Commission. Each volume serves, respectively, as the text for a course of instruction in a series of courses for NRC response personnel. These materials do not provide guidance or license requirements for NRC licensees. The volumes have been organized into these training modules to accommodate the scheduling and duty needs of participating NRC staff. Each volume is accompanied by an appendix of slides that can be used to present this material

Light and redox switchable molecular components for molecular electronics.

Science.gov (United States)

Browne, Wesley R; Feringa, Ben L

2010-01-01

The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerous unexpected challenges that have slowed progress and the initial promise of complex molecular-based computers has not yet been realised. Primarily this has been due to the realisation at an early stage that molecular-based nano-electronics brings with it the interface between the hard (semiconductor) and soft (molecular) worlds and the challenges which accompany working in such an environment. Issues such as addressability, cross-talk, molecular stability and perturbation of molecular properties (e.g., inhibition of photochemistry) have nevertheless driven development in molecular design and synthesis as well as our ability to interface molecular components with bulk metal contacts to a very high level of sophistication. Numerous groups have played key roles in progressing this field not least teams such as those led by Whitesides, Aviram, Ratner, Stoddart and Heath. In this short review we will however focus on the contributions from our own group and those of our collaborators, in employing diarylethene based molecular components.

Molecular basis of the triple negative breast cancer

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Ayse Feyda Nursal

2015-06-01

Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

Molecular cloning of human protein 4.2: A major component of the erythrocyte membrane

International Nuclear Information System (INIS)

Sung, L.A.; Chien, Shu; Lambert, K.; Chang, Longsheng; Bliss, S.A.; Bouhassira, E.E.; Nagel, R.L.; Schwartz, R.S.; Rybicki, A.C.

1990-01-01

Protein 4.2 (P4.2) comprises ∼5% of the protein mass of human erythrocyte (RBC) membranes. Anemia occurs in patients with RBCs deficient in P4.2, suggesting a role for this protein in maintaining RBC stability and integrity. The authors now report the molecular cloning and characterization of human RBC P4.2 cDNAs. By immunoscreening a human reticulocyte cDNA library and by using the polymerase chain reaction, two cDNA sequences of 2.4 and 2.5 kilobases (kb) were obtained. These cDNAs differ only by a 90-base-air insert in the longer isoform located three codons downstream from the putative initiation site. The 2.4- and 2.5-kb cDNAs predict proteins of ∼77 and ∼80 kDa, respectively, and the authenticity was confirmed by sequence identity with 46 amino acids of three cyanogen bromide-cleaved peptides of P4.2. Northern blot analysis detected a major 2.4-kb RNA species in reticulocytes. Isolation of two P4.2 cDNAs implies existence of specific regulation of P4.2 expression in human RBCs. Human RBC P4.2 has significant homology with human factor XIII subunit a and guinea pig liver transglutaminase. Sequence alignment of P4.2 with these two transglutaminases, however, revealed that P4.2 lacks the critical cysteine residue required for the enzymatic crosslinking of substrates

Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap

DEFF Research Database (Denmark)

Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N

2018-01-01

-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation...

Contractile Response of Bovine Lateral Saphenous Vein to Ergotamine Tartrate Exposed to Different Concentrations of Molecularly Imprinted Polymer

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Manoj B. Kudupoje

2018-01-01

Full Text Available Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA. Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP comparison. Norepinephrine normalized percent contractile response to increasing ETA exhibited a sigmoidal dose response (max: 88.47 and log of the effective molar concentration (EC50 (−log [ETA] of 6.66 ± 0.17 M. Although sample preparation time affected contractile response (p < 0.001, pre-myograph incubation temperature (39 vs. 21 °C, 1 h had no effect (p > 0.05. Isothermal adsorption showed a maximum adsorption of 3.27E-008 moles·mg−1 and affinity between 0.51 and 0.57 mg (R2: 0.83–0.92 for both polymers, with no significant difference between polymers (p > 0.05. No significant differences in maximum inhibitory (p = 0.96 and IC50 responses (p = 0.163 between MIP and NIP were noticed. Normalized percent contraction could be predicted from the in vitro adsorption data (R2 = 0.87, p < 0.01, for both polymers. These studies indicate that synthetic polymers are potentially effective adsorbents to mitigate ergot toxicity caused by ergot alkaloids, with little evidence of significant differences between MIP and NIP in aqueous media.

Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder.

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Meyer, Jacob D; Ellingson, Laura D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

2016-11-01

Exercise acutely improves mood in major depressive disorder (MDD). However, it is unknown whether benefits differ depending on whether exercise intensity is self-selected or prescribed. This study aimed to compare psychological and biological responses to preferred and prescribed steady-state exercise intensities to a patient-selected preferred intensity. Female adults (N = 24, age = 38.6 ± 14.0 yr) diagnosed with MDD completed four 30-min sessions of cycling exercise at three prescribed intensities (RPE of 11, 13, and 15) and one session with a self-selected intensity (preferred). Order was randomized and counterbalanced. Depressed mood (DM) was evaluated before, 10 min, and 30 min postexercise using the Profile of Mood States. Serum brain-derived neurotrophic factor (BDNF) was measured before and within 10 min postexercise. Changes in BDNF and DM for the preferred session were compared with the following prescribed sessions: 1) performed at the most similar intensity (matched on RPE; closest) and 2) with the greatest improvement in DM (greatest). Compared with the preferred session, improvement in DM was significantly larger after the greatest session (30 min postexercise: -11.8 ± 7.4 vs -3.4 ± 4.8), and the BDNF response was significantly greater after the closest session (5.4 ± 6.9 vs -1.4 ± 9.8 ng·mL). Permitting patients to select their own exercise intensity did not maximize improvements in mood. Further, preferred intensity exercise was also associated with a smaller BDNF response. Overall, the results suggest that exercise undertaken to improve mood should be prescribed on an individual basis in MDD and not necessarily based on the patient's preferred intensity. Clinicians, psychologists, and other practitioners should consider providing clear exercise intensity recommendations for symptom management in depression rather than allowing patients to self-select their intensity.

Peroxiredoxin 6 from the Antarctic emerald rockcod: molecular characterization of its response to warming.

Science.gov (United States)

Tolomeo, A M; Carraro, A; Bakiu, R; Toppo, S; Place, S P; Ferro, D; Santovito, G

2016-01-01

In the present study, we describe the purification and molecular characterization of two peroxiredoxins (Prdxs), referred to as Prdx6A and Prdx6B, from Trematomus bernacchii, a teleost widely distributed in many areas of Antarctica, that plays a pivotal role in the Antarctic food chain. The two putative amino acid sequences were compared with Prdx6 orthologs from other fish, highlighting a high percentage of identity and similarity with the respective variant, in particular for the residues that are essential for the characteristic peroxidase and phospholipase activities of these enzymes. Phylogenetic analyses suggest the appearance of the two prdx6 genes through a duplication event before the speciation that led to the differentiation of fish families and that the evolution of the two gene variants seems to proceed together with the evolution of fish orders and families. The temporal expression of Prdx6 mRNA in response to short-term thermal stress showed a general upregulation of prdx6b and inhibition of prdx6a, suggesting that the latter is the variant most affected by temperature increase. The variations of mRNA accumulation are more conspicuous in heart than the liver, probably related to behavioral changes of the specimens in response to elevated temperature. These data, together with the peculiar differences between the molecular structures of the two Prdx6s in T. bernacchii as well as in the tropical species Stegastes partitus, suggest an adaptation that allowed these poikilothermic aquatic vertebrates to colonize very different environments, characterized by different temperature ranges.

Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

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Elio A Cino

Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

Energy Technology Data Exchange (ETDEWEB)

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

2008-06-06

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

Molecular interactions between the olive and the fruit fly Bactrocera oleae

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Corrado Giandomenico

2012-06-01

Full Text Available Abstract Background The fruit fly Bactrocera oleae is the primary biotic stressor of cultivated olives, causing direct and indirect damages that significantly reduce both the yield and the quality of olive oil. To study the olive-B. oleae interaction, we conducted transcriptomic and proteomic investigations of the molecular response of the drupe. The identifications of genes and proteins involved in the fruit response were performed using a Suppression Subtractive Hybridisation technique and a combined bi-dimensional electrophoresis/nanoLC-ESI-LIT-MS/MS approach, respectively. Results We identified 196 ESTs and 26 protein spots as differentially expressed in olives with larval feeding tunnels. A bioinformatic analysis of the identified non-redundant EST and protein collection indicated that different molecular processes were affected, such as stress response, phytohormone signalling, transcriptional control and primary metabolism, and that a considerable proportion of the ESTs could not be classified. The altered expression of 20 transcripts was also analysed by real-time PCR, and the most striking differences were further confirmed in the fruit of a different olive variety. We also cloned the full-length coding sequences of two genes, Oe-chitinase I and Oe-PR27, and showed that these are wound-inducible genes and activated by B. oleae punctures. Conclusions This study represents the first report that reveals the molecular players and signalling pathways involved in the interaction between the olive fruit and its most damaging biotic stressor. Drupe response is complex, involving genes and proteins involved in photosynthesis as well as in the production of ROS, the activation of different stress response pathways and the production of compounds involved in direct defence against phytophagous larvae. Among the latter, trypsin inhibitors should play a major role in drupe resistance reaction.

Development and evaluation of a new simulation model for interactive training of the medical response to major incidents and disasters.

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Lennquist Montán, K; Hreckovski, B; Dobson, B; Örtenwall, P; Montán, C; Khorram-Manesh, A; Lennquist, S

2014-08-01

The need for and benefit of simulation models for interactive training of the response to major incidents and disasters has been increasingly recognized during recent years. One of the advantages with such models is that all components of the chain of response can be trained simultaneously. This includes the important communication/coordination between different units, which has been reported as the most common cause of failure. Very few of the presently available simulation models have been suitable for the simultaneous training of decision-making on all levels of the response. In this study, a new simulation model, originally developed for the scientific evaluation of methodology, was adapted to and developed for the postgraduate courses in Medical Response to Major Incidents (MRMI) organized under the auspices of the European Society for Trauma and Emergency Surgery (ESTES). The aim of the present study was to describe this development process, the model it resulted in, and the evaluation of this model. The simulation model was based on casualty cards giving all information normally available for the triage and primary management of traumatized patients. The condition of the patients could be changed by the instructor according to the time passed since the time of injury and treatments performed. Priority of the casualties as well as given treatments could be indicated on the cards by movable markers, which also gave the time required for every treatment. The exercises were run with real consumption of time and resources for all measures performed. The magnetized cards were moved by the trainees through the scene, through the transport lines, and through the hospitals where all functions were trained. For every patient was given the definitive diagnosis and the times within certain treatments had to be done to avoid preventable mortality and complications, which could be related to trauma-scores. The methodology was tested in nine MRMI courses with a total of

Evidence of major genes affecting stress response in rainbow trout using Bayesian methods of complex segregation analysis

DEFF Research Database (Denmark)

Vallejo, R L; Rexroad III, C E; Silverstein, J T

2009-01-01

As a first step toward the genetic mapping of QTL affecting stress response variation in rainbow trout, we performed complex segregation analyses (CSA) fitting mixed inheritance models of plasma cortisol by using Bayesian methods in large full-sib families of rainbow trout. To date, no studies have...... been conducted to determine the mode of inheritance of stress response as measured by plasma cortisol response when using a crowding stress paradigm and CSA in rainbow trout. The main objective of this study was to determine the mode of inheritance of plasma cortisol after a crowding stress....... The results from fitting mixed inheritance models with Bayesian CSA suggest that 1 or more major genes with dominant cortisol-decreasing alleles and small additive genetic effects of a large number of independent genes likely underlie the genetic variation of plasma cortisol in the rainbow trout families...

Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress.

Science.gov (United States)

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2017-04-01

Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies.

Science.gov (United States)

Bardhan, Jaydeep P; Jungwirth, Pavel; Makowski, Lee

2012-09-28

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular "linear response" model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution).

TIP-1 translocation onto the cell plasma membrane is a molecular biomarker of tumor response to ionizing radiation.

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Hailun Wang

2010-08-01

Full Text Available Tumor response to treatment has been generally assessed with anatomic and functional imaging. Recent development of in vivo molecular and cellular imaging showed promise in time-efficient assessment of the therapeutic efficacy of a prescribed regimen. Currently, the in vivo molecular imaging is limited with shortage of biomarkers and probes with sound biological relevance. We have previously shown in tumor-bearing mice that a hexapeptide (HVGGSSV demonstrated potentials as a molecular imaging probe to distinguish the tumors responding to ionizing radiation (IR and/or tyrosine kinase inhibitor treatment from those of non-responding tumors.In this study we have studied biological basis of the HVGGSSV peptide binding within the irradiated tumors by use of tumor-bearing mice and cultured cancer cells. The results indicated that Tax interacting protein 1 (TIP-1, also known as Tax1BP3 is a molecular target that enables the selective binding of the HVGGSSV peptide within irradiated xenograft tumors. Optical imaging and immunohistochemical staining indicated that a TIP-1 specific antibody demonstrated similar biodistribution as the peptide in tumor-bearing mice. The TIP-1 antibody blocked the peptide from binding within irradiated tumors. Studies on both of human and mouse lung cancer cells showed that the intracellular TIP-1 relocated to the plasma membrane surface within the first few hours after exposure to IR and before the onset of treatment associated apoptosis and cell death. TIP-1 relocation onto the cell surface is associated with the reduced proliferation and the enhanced susceptibility to the subsequent IR treatment.This study by use of tumor-bearing mice and cultured cancer cells suggested that imaging of the radiation-inducible TIP-1 translocation onto the cancer cell surface may predict the tumor responsiveness to radiation in a time-efficient manner and thus tailor radiotherapy of cancer.

BRCA1, FANCD2 and Chk1 are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells.

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Burdak-Rothkamm, Susanne; Rothkamm, Kai; McClelland, Keeva; Al Rashid, Shahnaz T; Prise, Kevin M

2015-01-28

Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

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Washington B. Cárdenas

2010-01-01

Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

Investigation of miR-1202, miR-135a, and miR-16 in Major Depressive Disorder and Antidepressant Response.

Science.gov (United States)

Fiori, Laura M; Lopez, Juan Pablo; Richard-Devantoy, Stéphane; Berlim, Marcelo; Chachamovich, Eduardo; Jollant, Fabrice; Foster, Jane; Rotzinger, Susan; Kennedy, Sidney H; Turecki, Gustavo

2017-08-01

Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response. We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed. In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment. Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Molecular dynamics simulations of lipid bilayers : major artifacts due to truncating electrostatic interactions

NARCIS (Netherlands)

Patra, M.; Karttunen, M.E.J.; Hyvönen, M.T.; Falck, E.; Lindqvist, P.; Vattulainen, I.

2003-01-01

We study the influence of truncating the electrostatic interactions in a fully hydrated pure dipalmitoylphosphatidylcholine (DPPC) bilayer through 20 ns molecular dynamics simulations. The computations in which the electrostatic interactions were truncated are compared to similar simulations using

Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

Science.gov (United States)

Kubis, N.; Levy, B.I.

2003-01-01

Summary Angiogenesis characterizes embryonic development, but also occurs in adulthood in physiological situations such as adaptation to muscle exercise, and in pathological conditions like cancer. Major advances have been made in understanding the molecular mechanisms responsible for vasculogenesis and angiogenesis, largely due to the use of “knock-out mice”, i.e. mice in which the gene coding for the protein under investigation has been inactivated. Interestingly, the same growth factors and their receptors are equally involved in the different aspects of vasculogenesis and angiogenesis during development and in adulthood. This review aims to describe in detail their respective roles and how interactions between them lead to a newly formed vessel. PMID:20591248

Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle

Science.gov (United States)

Pugh, Jamie K; Faulkner, Steve H; Jackson, Andrew P; King, James A; Nimmo, Myra A

2015-01-01

Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 × 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 × 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser473) decreased at 6 h in both trials (P HIIT (P HIIT with PGC-1α and PGC-1α-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1α-ex1b only (P HIIT versus RE at 2 and 6 h (P effect on protein signaling and mRNA expression, and suggest that HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations. PMID:25902785

Direct quantitative comparison of molecular responses in photodamaged human skin to fractionated and fully ablative carbon dioxide laser resurfacing.

Science.gov (United States)

Orringer, Jeffrey S; Sachs, Dana L; Shao, Yuan; Hammerberg, Craig; Cui, Yilei; Voorhees, John J; Fisher, Gary J

2012-10-01

Fractionated ablative laser resurfacing has become a widely used treatment modality. Its clinical results are often found to approach those of traditional fully ablative laser resurfacing. To directly compare the molecular changes that result from fractionated and fully ablative carbon dioxide (CO(2)) laser resurfacing in photodamaged human skin. Photodamaged skin of 34 adult volunteers was focally treated at distinct sites with a fully ablative CO(2) laser and a fractionated CO(2) laser. Serial skin samples were obtained at baseline and several time points after treatment. Real-time reverse transcriptase polymerase chain reaction technology and immunohistochemistry were used to quantify molecular responses to each type of laser treatment. Fully ablative and fractionated CO(2) laser resurfacing induced significant dermal remodeling and collagen induction. After a single treatment, fractionated ablative laser resurfacing resulted in collagen induction that was approximately 40% to 50% as pronounced as that induced by fully ablative laser resurfacing. The fundamental cutaneous responses that result from fully ablative and fractionated carbon dioxide laser resurfacing are similar but differ in magnitude and duration, with the fully ablative procedure inducing relatively greater changes including more pronounced collagen induction. However, the molecular data reported here provide substantial support for fractionated ablative resurfacing as an effective treatment modality for improving skin texture. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Comparative metatranscriptomics identifies molecular bases for the physiological responses of phytoplankton to varying iron availability.

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Marchetti, Adrian; Schruth, David M; Durkin, Colleen A; Parker, Micaela S; Kodner, Robin B; Berthiaume, Chris T; Morales, Rhonda; Allen, Andrew E; Armbrust, E Virginia

2012-02-07

In vast expanses of the oceans, growth of large phytoplankton such as diatoms is limited by iron availability. Diatoms respond almost immediately to the delivery of iron and rapidly compose the majority of phytoplankton biomass. The molecular bases underlying the subsistence of diatoms in iron-poor waters and the plankton community dynamics that follow iron resupply remain largely unknown. Here we use comparative metatranscriptomics to identify changes in gene expression associated with iron-stimulated growth of diatoms and other eukaryotic plankton. A microcosm iron-enrichment experiment using mixed-layer waters from the northeastern Pacific Ocean resulted in increased proportions of diatom transcripts and reduced proportions of transcripts from most other taxa within 98 h after iron addition. Hundreds of diatom genes were differentially expressed in the iron-enriched community compared with the iron-limited community; transcripts of diatom genes required for synthesis of photosynthesis and chlorophyll components, nitrate assimilation and the urea cycle, and synthesis of carbohydrate storage compounds were significantly overrepresented. Transcripts of genes encoding rhodopsins in eukaryotic phytoplankton were significantly underrepresented following iron enrichment, suggesting rhodopsins help cells cope with low-iron conditions. Oceanic diatoms appear to display a distinctive transcriptional response to iron enrichment that allows chemical reduction of available nitrogen and carbon sources along with a continued dependence on iron-free photosynthetic proteins rather than substituting for iron-containing functional equivalents present within their gene repertoire. This ability of diatoms to divert their newly acquired iron toward nitrate assimilation may underlie why diatoms consistently dominate iron enrichments in high-nitrate, low-chlorophyll regions.

Molecular characterization of some new E. coli strains theoretically responsible for both intestinal and extraintestinal infections

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Ghaleb Adwan

2016-06-01

Full Text Available Strains of E. coli are divided into 3 major groups; commensal strains, diarrheagenic (intestinal E. coli pathotypes and extraintestinal pathogenic E. coli. Extraintestinal pathogenic E. coli are unlike diarrheagenic pathotypes, they have not ability to cause intestinal disease in human, but they have normal ability for long-term colonization in the gut. This study aimed to spotlight on that intestinal and extraintestinal infections are not restricted to intestinal pathotypes and extraintestinal pathogenic E. coli, respectively. A total of 102 uropathogenic E. coli isolates were collected during 2012 and 2015. A multiplex PCR was used to detect phylogenetic groups, virulence factors for extraintestinal pathogenic E. coli and intestinal E. coli pathotypes genes. Results of this research showed that 12 (11.8% uropathogenic E. coli isolates had genes that are theoretically responsible for intestinal diseases, were 10 of these isolates belonged to phylogentic group D and 2 isolates to phylogentic group A. We conclude from these results, this is the first report on the molecular characterization of E. coli that theoretically can cause both intestinal and extraintestinal infections simultaneously. The presence of these strains has a great impact on public health. More studies are necessary before definitive conclusions if these strains are a different clone that theoretically have ability to cause both intestinal and extraintestinal infections and belonged to phylogenetic groups other than A and D. Products of diarrheagenic genes in UPEC strains need further studies to detect their effects in intestinal infections

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

Science.gov (United States)

Lei, Zhengdeng; Tan, Iain Beehuat; Das, Kakoli; Deng, Niantao; Zouridis, Hermioni; Pattison, Sharon; Chua, Clarinda; Feng, Zhu; Guan, Yeoh Khay; Ooi, Chia Huey; Ivanova, Tatiana; Zhang, Shenli; Lee, Minghui; Wu, Jeanie; Ngo, Anna; Manesh, Sravanthy; Tan, Elisabeth; Teh, Bin Tean; So, Jimmy Bok Yan; Goh, Liang Kee; Boussioutas, Alex; Lim, Tony Kiat Hon; Flotow, Horst; Tan, Patrick; Rozen, Steven G

2013-09-01

Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targeted agents. We compared gene expression patterns among 248 gastric tumors; using a robust method of unsupervised clustering, consensus hierarchical clustering with iterative feature selection, we identified 3 major subtypes. We developed a classifier for these subtypes and validated it in 70 tumors from a different population. We identified distinct genomic and epigenomic properties of the subtypes. We determined drug sensitivities of the subtypes in primary tumors using clinical survival data, and in cell lines through high-throughput drug screening. We identified 3 subtypes of gastric adenocarcinoma: proliferative, metabolic, and mesenchymal. Tumors of the proliferative subtype had high levels of genomic instability, TP53 mutations, and DNA hypomethylation. Cancer cells of the metabolic subtype were more sensitive to 5-fluorouracil than the other subtypes. Furthermore, in 2 independent groups of patients, those with tumors of the metabolic subtype appeared to have greater benefits with 5-fluorouracil treatment. Tumors of the mesenchymal subtype contain cells with features of cancer stem cells, and cell lines of this subtype are particularly sensitive to phosphatidylinositol 3-kinase-AKT-mTOR inhibitors in vitro. Based on gene expression patterns, we classified gastric cancers into 3 subtypes, and validated these in an independent set of tumors. The subgroups have differences in molecular and genetic features and response to therapy; this information might be used to select specific treatment approaches for patients with gastric cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

Directory of Open Access Journals (Sweden)

Bas Verbruggen

2016-01-01

Full Text Available Since its emergence in the 1990s, White Spot Disease (WSD has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV, a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

Molecular Adaptations to Social Defeat Stress and Induced Depression in Mice.

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Bondar, Natalya; Bryzgalov, Leonid; Ershov, Nikita; Gusev, Fedor; Reshetnikov, Vasiliy; Avgustinovich, Damira; Tenditnik, Mikhail; Rogaev, Evgeny; Merkulova, Tatiana

2018-04-01

Chronic stress is a risk factor for major depression. Social defeat stress is a well-validated murine model of depression. However, little is known about the gene activity dynamics during the development of a depression-like state. We analyzed the effects of social defeat stress of varying duration (10 and 30 days) on the behavioral patterns and prefrontal-cortex transcriptome of C57BL/6 mice. The 10-day exposure to social defeat stress resulted in a high level of social avoidance with no signs of depression-associated behavior. Most animals exposed to 30 days of social defeat stress demonstrated clear hallmarks of depression, including a higher level of social avoidance, increased immobility in the forced swimming test, and anhedonic behavior. The monitoring of transcriptome changes revealed widespread alterations in gene expression on the 10th day. Surprisingly, the expression of only a few genes were affected by the 30th day of stress, apparently due to a reversal of the majority of the early stress-induced changes to the original basal state. Moreover, we have found that glucocorticoid-sensitive genes are clearly stimulated targets on the 10th day of stress, but these genes stop responding to the elevated corticosterone level by the 30th day of stress. The majority of genes altered by the 30-day stress were downregulated, with the most relevant ones participating in chromatin modifications and neuroplasticity (e.g., guanine nucleotide exchange factors of the Rho-family of GTPases). Very different molecular responses occur during short-term and long-term social stress in mice. The early-stress response is associated with social avoidance and with upregulation and downregulation of many genes, including those related to signal transduction and cell adhesion pathways. Downregulation of a few genes, in particular, genes for histone-modifying methyltransferases, is a signature response to prolonged stress that induces symptoms of depression. Altogether, our data

Molecular Gas in a Submillimeter Galaxy at z = 4.5: Evidence for a Major Merger at 1 Billion Years after the Big Bang

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Schinnerer, E.; Carilli, C. L.; Capak, P.; Martinez-Sansigre, A.; Scoville, N. Z.; Smolčić, V.; Taniguchi, Y.; Yun, M. S.; Bertoldi, F.; Le Fevre, O.; de Ravel, L.

2008-12-01

We report the detection of CO molecular line emission in the z = 4.5 millimeter-detected galaxy COSMOS J100054+023436 (hereafter J1000+0234) using the IRAM Plateau de Bure interferometer (PdBI) and NRAO's Very Large Array (VLA). The 12CO(4-3) line as observed with PdBI has a full line width of ~1000 km s-1, an integrated line flux of 0.66 Jy km s-1, and a CO luminosity of 3.2 × 1010 L⊙. Comparison to the 3.3 σ detection of the CO(2-1) line emission with the VLA suggests that the molecular gas is likely thermalized to the J = 4-3 transition level. The corresponding molecular gas mass is 2.6 × 1010 M⊙ assuming an ULIRG-like conversion factor. From the spatial offset of the red- and blueshifted line peaks and the line width a dynamical mass of 1.1 × 1011 M⊙ is estimated assuming a merging scenario. The molecular gas distribution coincides with the rest-frame optical and radio position of the object while being offset by 0.5'' from the previously detected Lyα emission. J1000+0234 exhibits very typical properties for lower redshift (z ~ 2) submillimeter galaxies (SMGs) and thus is very likely one of the long sought after high-redshift (z > 4) objects of this population. The large CO(4-3) line width taken together with its highly disturbed rest-frame UV geometry suggest an ongoing major merger about a billion years after the big bang. Given its large star formation rate (SFR) of >1000 M⊙ yr-1 and molecular gas content this object could be the precursor of a "red and dead" elliptical observed at a redshift of z = 2. Based on observations carried out with the IRAM Plateau de Bure Interferometer. IRAM is supported by INSU/CNRS (France), MPG (Germany), and IGN (Spain).

Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

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Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

2018-06-01

Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation

Molecular similarity measures.

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Maggiora, Gerald M; Shanmugasundaram, Veerabahu

2011-01-01

Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide

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Sugimoto Yuka

2012-03-01

Full Text Available Abstract Background While lenalidomide (LEN shows high efficacy in myelodysplastic syndromes (MDS with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN, MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML without del[5q] by metaphase cytogenetics (MC who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH or single nucleotide polymorphism array (SNP-A-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8% additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08 and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11. However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.

Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

Science.gov (United States)

Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

2008-01-01

Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

Evolutionary molecular medicine.

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Nesse, Randolph M; Ganten, Detlev; Gregory, T Ryan; Omenn, Gilbert S

2012-05-01

Evolution has long provided a foundation for population genetics, but some major advances in evolutionary biology from the twentieth century that provide foundations for evolutionary medicine are only now being applied in molecular medicine. They include the need for both proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, competition between alleles, co-evolution, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are transforming evolutionary biology in ways that create even more opportunities for progress at its interfaces with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine.

Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

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Mary E. Peek

2012-01-01

Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

Development of self-assembled molecular structures on polymeric surfaces and their applications as ultrasonically responsive barrier coatings for on-demand, pulsatile drug delivery

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Kwok, Connie Sau-Kuen

Nature in the form of DNA, proteins, and cells has the remarkable ability to interact with its environment by processing biological information through specific molecular recognition at the interface. As such, materials that are capable of triggering an appropriate biological response need to be engineered at the biomaterial surface. Chemically and structurally well-defined self-assembled monolayers (SAMs), biomimetics of the lipid bilayer in cell membranes, have been created and studied mostly on rigid metallic surfaces. This dissertation is motivated by the lack of methods to generate a molecularly designed surface for biomedical polymers and thus provides an enabling technology to engineer a polymeric surface precisely at a molecular and cellular level. To take this innovation one step further, we demonstrated that such self-assembled molecular structure coated on drug-containing polymeric devices could act as a stimulus-responsive barrier for controlled drug delivery. A simple, one-step procedure for generating ordered, crystalline methylene chains on polymeric surfaces via urethane linkages was successfully developed. The self-assemblies and molecular structures of these crystalline methylene chains are comparable to the SAM model surfaces, as evidenced by various surface characterization techniques (XPS, TOF-SIMS, and FTIR-ATR). For the first time, these self-assembled molecular structures are shown to function collectively as an ultrasound-responsive barrier membrane for pulsatile drug delivery, including delivery of low-molecular-weight ciprofloxacin and high-molecular-weight insulin. Encouraging results, based on the insulin-activated deoxyglucose uptakes in adipocytes, indicate that the released insulin remained biologically active. Both chemical and acoustic analyses suggest that the ultrasound-assisted release mechanism is primarily induced by transient cavitation, which causes temporary disruption of the self-assembled overlayer, and thus allows

High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.

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You, Qingping; Zhang, Yuping; Zhang, Qingwen; Guo, Junfang; Huang, Weihua; Shi, Shuyun; Chen, Xiaoqin

2014-08-08

Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of Molecular Modeling & Simulation

Energy Technology Data Exchange (ETDEWEB)

None

2002-01-03

This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

Science.gov (United States)

Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

2016-08-01

Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

Recent Advances in the Molecular Characterization of Circulating Tumor Cells

Energy Technology Data Exchange (ETDEWEB)

Lowes, Lori E. [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Allan, Alison L., E-mail: alison.allan@lhsc.on.ca [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Lawson Health Research Institute, London, ON N6C 2R5 (Canada)

2014-03-13

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch{sup ®} system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing.

Recent Advances in the Molecular Characterization of Circulating Tumor Cells

International Nuclear Information System (INIS)

Lowes, Lori E.; Allan, Alison L.

2014-01-01

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch ® system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing

MOLECULARLY IMPRINTED POLYMER TECHNOLOGY: A ...

African Journals Online (AJOL)

dell

Cross-linking ensures polymer rigidity that “freezes” the 3-D molecular architecture of the binding cavity when the ... molecular technology applications whose potential is still .... recognition element is responsible for the selective ... organic treatments, making them superior ... efficiency with which such materials may be.

Event-related potentials in response to emotional words in patients with major depressive disorder and healthy controls.

Science.gov (United States)

Liu, Hong; Yin, Hui-fang; Wu, Da-xing; Xu, Shu-jing

2014-01-01

Dysfunctional cognitive processing and abnormal brain activation in response to emotional stimuli have long been recognized as core features of the major depressive disorder (MDD). The aim of this study was to examine how Chinese patients with MDD process Chinese emotional words presented to either the left (LH) or right hemisphere (RH). Reaction time (RT) and the late positive component of the event-related potential were measured while subjects judged the valence (positive or negative) of emotional words written in Chinese. Compared to healthy controls, patients with MDD exhibited slower RTs in response to negative words. In all subjects, the RTs in response to negative words were significantly faster than RTs in response to positive words presented to the LH, as well as significantly faster than responses to negative words presented to the RH. Compared to healthy controls, MDD patients exhibited reduced activation of the central and left regions of the brain in response to both negative and positive words. In healthy controls, the posterior brain areas were more active than the anterior brain areas when responding to negative words. All individuals showed faster RTs in response to negative words compared to positive words. In addition, MDD patients showed lateralization of brain activity in response to emotional words, whereas healthy individuals did not show this lateralization. Posterior brain areas appear to play an especially important role in discriminating and experiencing negative emotional words. This study provides further evidence in support of the negative bias hypothesis and the emotional processing theory.

Affine-response model of molecular solvation of ions: Accurate predictions of asymmetric charging free energies

Science.gov (United States)

Bardhan, Jaydeep P.; Jungwirth, Pavel; Makowski, Lee

2012-01-01

Two mechanisms have been proposed to drive asymmetric solvent response to a solute charge: a static potential contribution similar to the liquid-vapor potential, and a steric contribution associated with a water molecule's structure and charge distribution. In this work, we use free-energy perturbation molecular-dynamics calculations in explicit water to show that these mechanisms act in complementary regimes; the large static potential (∼44 kJ/mol/e) dominates asymmetric response for deeply buried charges, and the steric contribution dominates for charges near the solute-solvent interface. Therefore, both mechanisms must be included in order to fully account for asymmetric solvation in general. Our calculations suggest that the steric contribution leads to a remarkable deviation from the popular “linear response” model in which the reaction potential changes linearly as a function of charge. In fact, the potential varies in a piecewise-linear fashion, i.e., with different proportionality constants depending on the sign of the charge. This discrepancy is significant even when the charge is completely buried, and holds for solutes larger than single atoms. Together, these mechanisms suggest that implicit-solvent models can be improved using a combination of affine response (an offset due to the static potential) and piecewise-linear response (due to the steric contribution). PMID:23020318

Fabrication of Thermo-Responsive Molecular Layers from Self-Assembling Elastin-Like Oligopeptides Containing Cell-Binding Domain for Tissue Engineering

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Tomoyuki Koga

2015-01-01

Full Text Available Novel thermo-responsive elastin-like oligopeptides containing cell-binding epitope (Arg-Gly-Asp-Ser sequence; arginine-glycine-aspartic acid-serine (RGDS-elastin-like peptides (ELP and RGDS-deg-ELP; were newly prepared as building blocks of self-assembled molecular layer for artificial extra cellular matrix. A detailed analysis of the conformation of the oligo(ELPs in water and their self-assembling behavior onto hydrophobic surfaces were performed by using circular dichroism, Fourier transform infrared spectroscopy (FTIR, atomic force microscopy and water contact angle measurements. The experimental results revealed that both oligo(ELPs self-assembled onto hydrophobic surfaces and formed molecular layers based on their thermo-responsive conformational change from hydrous random coil to dehydrated β-turn structure. Effective cell adhesion and spreading behaviors were observed on these self-assembled oligo(ELP layers. In addition, attached cells were found to be recovered successfully as a cell-sheet by temperature-induced disassembly of oligo(ELP layer. This achievement provides an important insight to construct novel oligopeptide-based nano-surfaces for the design of smart artificial extra-cellular matrix.

Comparative transcriptomic analysis reveals that Ethylene/H2O2-mediated hypersensitive response and program cell death determine the compatible interaction of Sand pear and Alternaria Alternata

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A major production restriction on sand pear (Pyrus pyrifolia) is black spot disease caused by the necrotrophic fungus Alternaria alternata. However, pear response mechanism to A. alternata is unknown at molecular level. Here, host responses of a resistant cultivar Cuiguan (CG) and a susceptible cult...

Evidence of major genes for exercise heart rate and blood pressure at baseline and in response to 20 weeks of endurance training: the HERITAGE family study.

Science.gov (United States)

An, P; Borecki, I B; Rankinen, T; Pérusse, L; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2003-10-01

Major gene effects on exercise heart rate (HR) and blood pressure (BP) measured at 50 W and 80 % maximal oxygen uptake (VO (2)max) were assessed in 99 White families in the HERITAGE Family Study. Exercise HR and BP were measured both before and after 20 weeks of endurance training. The baseline phenotypes were adjusted for the effects of age and BMI, whereas the training responses (post-training minus baseline) were adjusted for the effects of age, BMI and the corresponding baseline values, within four sex-by-generation groups. Baseline exercise HR at 50 W was under the influence of a major recessive gene and a multifactorial component, which accounted for 30 % and 27 % of the variance, respectively. The training response was found to be under the influence of a major dominant gene, which accounted for 27 % of the variance. These significant major gene effects were independent of the effects of cigarette smoking, baseline VO (2)max, and the resting HR levels. No significant interactions were found between genotype and age, sex, or BMI. No major gene effect was found for exercise BP. Instead, we found the baseline exercise BP at 50 W and 80 % VO (2)max and the training response at 50 W were solely influenced by multifactorial effects, which accounted for about 50 %, 40 % and 20 % of the variance, respectively. No familial resemblance was found for training responses in exercise HR or BP at 80 % VO (2)max. Segregation analysis also was carried out for exercise HR in Whites pooled with a small sample of Blacks in HERITAGE. Similar major effects were found, but the transmission from parents to offspring did not follow Mendelian expectations, suggesting sample heterogeneity. In conclusion, submaximal exercise HR at baseline and in response to endurance training was influenced by putative major genes, with no evidence of interactions with sex, age or BMI, in contrast to a multifactorial etiology for exercise BP.

Semuloparin for prevention of venous thromboembolism after major orthopedic surgery

DEFF Research Database (Denmark)

Lassen, M R; Fisher, W; Mouret, P

2012-01-01

BACKGROUND: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients. OBJECTIVES: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic...... was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM...

Molecular Force Spectroscopy on Cells

Science.gov (United States)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

Detect the sensitivity and response of protein molecular structure of whole canola seed (yellow and brown) to different heat processing methods and relation to protein utilization and availability using ATR-FT/IR molecular spectroscopy with chemometrics.

Science.gov (United States)

Samadi; Theodoridou, Katerina; Yu, Peiqiang

2013-03-15

The objectives of this experiment were to detect the sensitivity and response of protein molecular structure of whole canola seed to different heat processing [moisture (autoclaving) vs. dry (roasting) heating] and quantify heat-induced protein molecular structure changes in relation to protein utilization and availability. In this study, whole canola seeds were autoclaved (moisture heating) and dry (roasting) heated at 120 °C for 1h, respectively. The parameters assessed included changes in (1) chemical composition profile, (2) CNCPS protein subfractions (PA, PB1, PB2, PB3, PC), (3) intestinal absorbed true protein supply, (4) energy values, and (5) protein molecular structures (amide I, amide II, ratio of amide I to II, α-helix, β-sheet, ratio of α-helix to β-sheet). The results showed that autoclave heating significantly decreased (Pseed. Future study is needed to study response and impact of heat processing to each inherent layer of canola seed from outside to inside tissues and between yellow canola and brown canola. Copyright © 2012 Elsevier B.V. All rights reserved.

Transcriptome dynamics of a susceptible wheat upon Fusarium head blight reveals that molecular responses to Fusarium graminearum infection fit over the grain development processes.

Science.gov (United States)

Chetouhi, Cherif; Bonhomme, Ludovic; Lasserre-Zuber, Pauline; Cambon, Florence; Pelletier, Sandra; Renou, Jean-Pierre; Langin, Thierry

2016-03-01

In many plant/pathogen interactions, host susceptibility factors are key determinants of disease development promoting pathogen growth and spreading in plant tissues. In the Fusarium head blight (FHB) disease, the molecular basis of wheat susceptibility is still poorly understood while it could provide new insights into the understanding of the wheat/Fusarium graminearum (Fg) interaction and guide future breeding programs to produce cultivars with sustainable resistance. To identify the wheat grain candidate genes, a genome-wide gene expression profiling was performed in the French susceptible wheat cultivar, Recital. Gene-specific two-way ANOVA of about 40 K transcripts at five grain developmental stages identified 1309 differentially expressed genes. Out of these, 536 were impacted by the Fg effect alone. Most of these Fg-responsive genes belonged to biological and molecular functions related to biotic and abiotic stresses indicating the activation of common stress pathways during susceptibility response of wheat grain to FHB. This analysis revealed also 773 other genes displaying either specific Fg-responsive profiles along with grain development stages or synergistic adjustments with the grain development effect. These genes were involved in various molecular pathways including primary metabolism, cell death, and gene expression reprogramming. An increasingly complex host response was revealed, as was the impact of both Fg infection and grain ontogeny on the transcription of wheat genes. This analysis provides a wealth of candidate genes and pathways involved in susceptibility responses to FHB and depicts new clues to the understanding of the susceptibility determinism in plant/pathogen interactions.

Molecular Mechanisms of DNA Replication Checkpoint Activation

Directory of Open Access Journals (Sweden)

Bénédicte Recolin

2014-03-01

Full Text Available The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.

Cellular and molecular immune responses of the sea bass (Dicentrarchus labrax) experimentally infected with betanodavirus

DEFF Research Database (Denmark)

Scapigliati, G.; Buonocore, F.; Randelli, E.

2010-01-01

and acquired responses: type I IFN, Mx, IL-1, Cox-2; IL-10, TGF-β, TCRβ, CD4, CD8α, IgM, by using a quantitative PCR array system developed for sea bass. The obtained results showed a detectable increase of T cells and B cells in PBL during betanodavirus infection. Furthermore, leucocytes obtained from blood...... was also observed, while the other tested genes did not show any significant variations with respect to mock-treated fish. Overall, our work represents a first comprehensive analysis of cellular and molecular immune parameters in a fish species exposed to a pathogenic virus....

Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy

International Nuclear Information System (INIS)

Ramesh, V.; McClatchey, A.I.; Ramesh, N.; Benoit, L.A.; Berson, E.L.; Shih, V.E.; Gusella, J.F.

1988-01-01

Gyrate atrophy (GA), a recessive eye disease involving progressive loss of vision due to chorioretinal degeneration, is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase with consequent hyperornithinemia. Genetic heterogeneity of GA has been suggested by the demonstration that administration of pyridoxine to increase the level of pyridoxal phosphate, a cofactor of OATase, reduces hyperornithinemia in a subset of patients. The authors have cloned and sequences cDNAs for OATase from two GA patients, one responsive and one nonresponsive to pyridoxine treatment. The respective cDNAs contained different single missense mutations, which were sufficient to eliminate OATase activity when each cDNA was tested in a eukaryotic expression system. However, like the enzyme in fibroblasts from the pyridoxine-responsive patient, OATase encoded by the corresponding cDNA from this individual showed a significant increase in activity when assayed in the presence of an increased pyridoxal phosphate concentration. These data firmly establish that both pyridoxine responsive and nonresponsive forms of GA result from mutations in the OATase structural gene. Moreover, they provide a molecular characterization of the primary lesion in a pyridoxine-responsive genetic disorder

In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer.

Directory of Open Access Journals (Sweden)

Ryohei Miyazaki

Full Text Available Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs and anaplastic lymphoma kinase (ALK inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI test and collagen gel droplet embedded culture drug sensitivity test (CD-DST are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.The growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.HCC827 (Exon19: E746-A750 del and H3122 (EML4-ALK cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003. The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026 in CD-DST.In vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

Molecular Selectivity of Brown Carbon Chromophores

Energy Technology Data Exchange (ETDEWEB)

Laskin, Julia; Laskin, Alexander; Nizkorodov, Sergey; Roach, Patrick J.; Eckert, Peter A.; Gilles, Mary K.; Wang, Bingbing; Lee, Hyun Ji; Hu, Qichi

2014-10-21

Complementary methods of high-resolution mass spectrometry and micro-spectroscopy were utilized for molecular analysis of secondary organic aerosol (SOA) generated from ozonolysis of two structural monoterpene isomers: D-limonene (LSOA) and a-pinene (PSOA). Laboratory simulated aging of LSOA and PSOA, through conversion of carbonyls into imines mediated by NH3 vapors in humid air, resulted in selective browning of the LSOA sample, while the PSOA sample remained white. Comparative analysis of the reaction products in the aged LSOA and PSOA samples provided insights into chemistry relevant to formation of brown carbon chromophores. A significant fraction of carbonyl-imine conversion products with identical molecular formulas were detected in both samples. This reflects the high level of similarity in the molecular composition of these two closely related SOA materials. Several highly conjugated products were detected exclusively in the brown LSOA sample and were identified as potential chromophores responsible for the observed color change. The majority of the unique products in the aged LSOA sample with the highest number of double bonds contain two nitrogen atoms. We conclude that chromophores characteristic of the carbonyl- imine chemistry in LSOA are highly conjugated oligomers of secondary imines (Schiff bases) present at relatively low concentrations. Formation of this type of conjugated compounds in PSOA is hindered by the structural rigidity of the a-pinene oxidation products. Our results suggest that the overall light-absorbing properties of SOA may be determined by trace amounts of strong brown carbon chromophores.

Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

Science.gov (United States)

Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

2016-01-01

Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

GWAS-based machine learning approach to predict duloxetine response in major depressive disorder.

Science.gov (United States)

Maciukiewicz, Malgorzata; Marshe, Victoria S; Hauschild, Anne-Christin; Foster, Jane A; Rotzinger, Susan; Kennedy, James L; Kennedy, Sidney H; Müller, Daniel J; Geraci, Joseph

2018-04-01

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders and is commonly treated with antidepressant drugs. However, large variability is observed in terms of response to antidepressants. Machine learning (ML) models may be useful to predict treatment outcomes. A sample of 186 MDD patients received treatment with duloxetine for up to 8 weeks were categorized as "responders" based on a MADRS change >50% from baseline; or "remitters" based on a MADRS score ≤10 at end point. The initial dataset (N = 186) was randomly divided into training and test sets in a nested 5-fold cross-validation, where 80% was used as a training set and 20% made up five independent test sets. We performed genome-wide logistic regression to identify potentially significant variants related to duloxetine response/remission and extracted the most promising predictors using LASSO regression. Subsequently, classification-regression trees (CRT) and support vector machines (SVM) were applied to construct models, using ten-fold cross-validation. With regards to response, none of the pairs performed significantly better than chance (accuracy p > .1). For remission, SVM achieved moderate performance with an accuracy = 0.52, a sensitivity = 0.58, and a specificity = 0.46, and 0.51 for all coefficients for CRT. The best performing SVM fold was characterized by an accuracy = 0.66 (p = .071), sensitivity = 0.70 and a sensitivity = 0.61. In this study, the potential of using GWAS data to predict duloxetine outcomes was examined using ML models. The models were characterized by a promising sensitivity, but specificity remained moderate at best. The inclusion of additional non-genetic variables to create integrated models may improve prediction. Copyright © 2017. Published by Elsevier Ltd.

Interplay of single particle and collective response in molecular dynamics simulation of dusty plasma system

Science.gov (United States)

Maity, Srimanta; Das, Amita; Kumar, Sandeep; Tiwari, Sanat Kumar

2018-04-01

The collective response of the plasma medium is well known and has been explored extensively in the context of dusty plasma medium. On the other hand, the individual particle response associated with the collisional character giving rise to the dissipative phenomena has not been explored adequately. In this paper, two-dimensional molecular dynamics simulation of dust particles interacting via Yukawa potential has been considered. It has been shown that disturbances induced in a dust crystal elicit both collective and single particle responses. Generation of a few particles moving at speeds considerably higher than acoustic and/or shock speed (excited by the external disturbance) is observed. This is an indication of a single particle response. Furthermore, as these individual energetic particles propagate, the dust crystal is observed to crack along their path. Initially when the energy is high, these particles generate secondary energetic particles by the collisional scattering process. However, ultimately as these particles slow down they excite a collective response in the dust medium at secondary locations in a region which is undisturbed by the primary external disturbance. The condition when the cracking of the crystal stops and collective excitations get initiated has been identified quantitatively. The trailing collective primary disturbances would thus often encounter a disturbed medium with secondary and tertiary collective perturbations, thereby suffering significant modification in its propagation. It is thus clear that there is an interesting interplay (other than mere dissipation) between the single particle and collective response which governs the dynamics of any disturbance introduced in the medium.

Nickel and binary metal mixture responses in Daphnia magna: Molecular fingerprints and (sub)organismal effects

International Nuclear Information System (INIS)

Vandenbrouck, Tine; Soetaert, Anneleen; Ven, Karlijn van der; Blust, Ronny; Coen, Wim de

2009-01-01

The recent development of a custom cDNA microarray platform for one of the standard organisms in aquatic toxicology, Daphnia magna, opened up new ways to mechanistic insights of toxicological responses. In this study, the mRNA expression of several genes and (sub)organismal responses (Cellular Energy Allocation, growth) were assayed after short-term waterborne metal exposure. Microarray analysis of Ni-exposed daphnids revealed several affected functional gene classes, of which the largest ones were involved in different metabolic processes (mainly protein and chitin related processes), cuticula turnover, transport and signal transduction. Furthermore, transcription of genes involved in oxygen transport and heme metabolism (haemoglobin, δ-aminolevilunate synthase) was down-regulated. Applying a Partial Least Squares regression on nickel fingerprints and biochemical (sub)organismal parameters revealed a set of co-varying genes (haemoglobin, RNA terminal phosphate cyclase, a ribosomal protein and an 'unknown' gene fragment). An inverse relationship was seen between the mRNA expression levels of different cuticula proteins and available energy reserves. In addition to the nickel exposure, daphnids were exposed to binary mixtures of nickel and cadmium or nickel and lead. Using multivariate analysis techniques, the mixture mRNA expression fingerprints (Ni 2+ + Cd 2+ , Ni 2+ + Pb 2+ ) were compared to those of the single metal treatments (Ni 2+ , Cd 2+ , Pb 2+ ). It was hypothesized that the molecular fingerprints of the mixtures would be additive combinations of the gene transcription profiles of the individual compounds present in the mixture. However, our results clearly showed additionally affected pathways after mixture treatment (e.g. additional affected genes involved in carbohydrate catabolic processes and proteolysis), indicating interactive molecular responses which are not merely the additive sum of the individual metals. These findings, although indicative of

Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients.

Science.gov (United States)

Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Kawano, Aimi; Ando, Tomoko; Okamoto, Shizuko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Kodama, Kensuke; Isogawa, Koichi; Akiyoshi, Jotaro

2012-03-30

Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary α-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD. Copyright © 2011 Elsevier Inc. All rights reserved.

Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

Science.gov (United States)

Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

Response style, interpersonal difficulties and social functioning in major depressive disorder.

Science.gov (United States)

Lam, Dominic; Schuck, Nikki; Smith, Neil; Farmer, Anne; Checkley, Stuart

2003-08-01

It is postulated that depressed patients who engaged in self-focused rumination on their depressive symptoms may experience more hopelessness, more interpersonal distress and poorer social functioning while patients who distract themselves may experience less severe hopelessness and better social functioning. One-hundred and nine outpatients suffering from DSM-IV (APA, 1994) major depressive disorders filled in questionnaires that mapped into their response style to depression, hopelessness and interpersonal style. They were also interviewed for their levels of social functioning. Rumination was associated with higher levels of depression and distraction was associated with lower levels of depression. Furthermore when levels of depression and gender were controlled for, rumination contributed to higher levels of hopelessness and distraction contributed to lower levels of hopelessness. Both rumination and levels of depression contributed significantly to higher levels of interpersonal distress when gender was controlled for. Ruminators were rated to have significantly more severe problems in intimate relationships while distractors were rated to have significantly higher social functioning. Our study suggests the importance of teaching patients techniques to distract themselves. This could prevent patients from getting into a vicious cycle of self-absorption and increased levels of hopelessness, finding it hard to interact with people in their social network and neglecting their intimate relationships.

A comprehensive study into the molecular methodology and molecular biology of methanogenic Archaea

DEFF Research Database (Denmark)

Lange, M.; Ahring, Birgitte Kiær

2001-01-01

Methanogens belong to the kingdom of Euryarchaeota in the domain of Archaea. The Archaea differ from Bacteria in many aspects important to molecular work. Among these are cell wall composition, their sensitivity to antibiotics, their translation and transcription machinery, and their very strict ...... procedures. Efficient genetic manipulation systems, including shuttle and integration vector systems, have appeared for mesophilic, but not for thermophilic species within the last few years and will have a major impact on future investigations of methanogenic molecular biology....

Photo-cured pH-responsive polyampholyte-coated membranes for controlled release of drugs with different molecular weights and charges

International Nuclear Information System (INIS)

Ng, Loo-Teck; Ng, Kheng-Seong

2008-01-01

Intelligent drug delivery membranes were synthesised by photocuring poly(acrylic acid) (PAA) or polyampholytes comprised of copolymers of acrylic acid (AA)/2-(diethylamino)ethyl methacrylate (DEAEMA) with varying monomeric compositions onto poly(2-hydroxyethyl methacrylate) (PHEMA) membranes, each with model drugs of different molecular weights and charges being incorporated. pH-responsive release behaviours of the model drugs which included methylene blue (cationic), metanil yellow (anionic) and caffeine (neutral) were studied. Only membranes with methylene blue and caffeine incorporated displayed clear pH-responsive releases though all coatings. This study demonstrates that drug diffusion through pH-responsive membranes depends to a large extent on the attractive interaction between the drug and the appropriate functional group/s in the coating

Major depression is not associated with blunting of aversive responses; evidence for enhanced anxious anticipation.

Directory of Open Access Journals (Sweden)

Christian Grillon

Full Text Available According to the emotion-context insensitivity (ECI hypothesis, major depressive disorder (MDD is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5±10.4 years were compared with 28 controls (35.1±7.4 years. Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005 of the variance in patients' startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD.

Major Depression Is Not Associated with Blunting of Aversive Responses; Evidence for Enhanced Anxious Anticipation

Science.gov (United States)

Grillon, Christian; Franco-Chaves, Jose A.; Mateus, Camilo F.; Ionescu, Dawn F.; Zarate, Carlos A.

2013-01-01

According to the emotion-context insensitivity (ECI) hypothesis, major depressive disorder (MDD) is associated with a diminished ability to react emotionally to positive stimuli and with blunting of defensive responses to threat. That defensive responses are blunted in MDD seems inconsistent with the conceptualization and diagnostic nosology of MDD. The present study tested the ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients with MDD (35.5±10.4 years) were compared with 28 controls (35.1±7.4 years). Participants were exposed to three conditions: no shock, predictable shock, and unpredictable shock. Startle magnitude was used to assess defensive responses. Inconsistent with the ECI hypothesis, startle potentiation to predictable and unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed elevated startle throughout testing as well as increased contextual anxiety during the placement of the shock electrodes and in the predictable condition. A regression analysis indicated that illness duration and Beck depression inventory scores explained 37% (p<.005) of the variance in patients’ startle reactivity. MDD is not associated with emotional blunting but rather enhanced defensive reactivity during anticipation of harm. These results do not support a strong version of the ECI hypothesis. Understanding the nature of stimuli or situations that lead to blunted or enhanced defensive reactivity will provide better insight into dysfunctional emotional experience in MDD. PMID:23951057

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

Science.gov (United States)

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed

Investigation of the molecular level interactions between mucins and food proteins: Spectroscopic, tribological and rheological studies

OpenAIRE

Celebioglu, Hilal Yilmaz; Chronakis, Ioannis S.; Lee, Seunghwan; Guðjónsdóttir, María

2017-01-01

The thesis investigated the structure and molecular-level interaction of β-lactoglobulin (BLG) and mucins, representing major components of the dairy products and saliva/digestion systems, respectively. Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer covers epithelial surfaces throughout the body. A literature review of the interactions of different mucin types and saliva mucins with several food proteins and food protein emulsions, as well as their f...

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

Science.gov (United States)

Seiler, Roland; Ashab, Hussam Al Deen; Erho, Nicholas; van Rhijn, Bas W G; Winters, Brian; Douglas, James; Van Kessel, Kim E; Fransen van de Putte, Elisabeth E; Sommerlad, Matthew; Wang, Natalie Q; Choeurng, Voleak; Gibb, Ewan A; Palmer-Aronsten, Beatrix; Lam, Lucia L; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A; Lerner, Seth P; McConkey, David J; Choi, Woonyoung; Kim, William Y; Kiss, Bernhard; Thalmann, George N; Todenhöfer, Tilman; Crabb, Simon J; North, Scott; Zwarthoff, Ellen C; Boormans, Joost L; Wright, Jonathan; Dall'Era, Marc; van der Heijden, Michiel S; Black, Peter C

2017-10-01

An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Gene expression analysis was used to assign subtypes. Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Different molecular

The human intestinal IgA response; burning questions.

Directory of Open Access Journals (Sweden)

Jo eSpencer

2012-05-01

Full Text Available Understanding the cellular and molecular mechanisms that generate the human intestinal IgA response is fundamentally important if effective mucosal vaccination is to be successful and broadly applied. There have been several major advances in this field recently that have allowed us to feel optimistic that this will be achieved. However, there are still many unanswered questions. These questions have been used as a scaffold for this review that considers findings at the current leading edge alongside the many uncertainties in this field.

Light and Redox Switchable Molecular Components for Molecular Electronics

NARCIS (Netherlands)

Browne, Wesley R.; Feringa, Bernard

2010-01-01

The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen

The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects

DEFF Research Database (Denmark)

Domdey, A.; Liu, A.; Millner, A.

2010-01-01

in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated...... from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-beta on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4(+)CD25(+) T cells...... in PBMCs in the two groups, but fewer cells from atopic donors were CD4(+)CD25(+)CCR4(+) and more cells were CD4(+)CD25(+)CLA(+) compared to healthy donors. Conclusion: Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced...

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

Science.gov (United States)

Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2005-02-01

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Exercise Attenuates the Major Hallmarks of Aging

Science.gov (United States)

Garatachea, Nuria; Pareja-Galeano, Helios; Santos-Lozano, Alejandro; Fiuza-Luces, Carmen; Morán, María; Emanuele, Enzo; Joyner, Michael J.; Lucia, Alejandro

2015-01-01

Abstract Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people. PMID:25431878

Cardiovascular molecular imaging of apoptosis

International Nuclear Information System (INIS)

Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

2007-01-01

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Cardiovascular molecular imaging of apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

2007-06-15

Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

Science.gov (United States)

Wichmann, Susann; Kirschbaum, Clemens; Böhme, Carsten; Petrowski, Katja

2017-09-01

Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo-response

Molecular markers for thyroid cancer

International Nuclear Information System (INIS)

Marrero Rodriguez, Maria Teresa; Sinconegui Gomez, Belkys; Cruz Cruz, Anaisa

2015-01-01

The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more accessible and potentially usable from a methodological viewpoint for diagnosis of the thyroid nodule before surgery. The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more

Baseline blood immunological profiling differentiates between Her2-breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response.

Science.gov (United States)

Tudoran, Oana; Virtic, Oana; Balacescu, Loredana; Lisencu, Carmen; Fetica, Bogdan; Gherman, Claudia; Balacescu, Ovidiu; Berindan-Neagoe, Ioana

2015-01-01

Breast cancer patients' response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients' clinicopathological characteristics. Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status. We observed that more patients with estrogen (ER)/progesterone (PR)-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL26; and cytokines: CSF2, IFNA2, OSM, TNSF13. The expression levels of these genes have been previously shown to be associated with reduced immunological status; indeed, the triple-negative breast cancer patients presented with lower counts of lymphocytes and eosinophils than the ER/PR-positive ones. These results contribute to a better understanding of the possible role of antitumor immune responses in mediating the clinical outcome.

Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

Science.gov (United States)

Forrest, Kerrie L; Bhave, Mrinal

2007-10-01

The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry.

Molecular Analysis and Genomic Organization of Major DNA Satellites in Banana (Musa spp.)

Czech Academy of Sciences Publication Activity Database

Čížková, Jana; Hřibová, Eva; Humplíková, Lenka; Christelová, Pavla; Suchánková, Pavla; Doležel, Jaroslav

2013-01-01

Roč. 8, č. 1 (2013) E-ISSN 1932-6203 R&D Projects: GA AV ČR KJB500380901; GA MŠk(CZ) LG12021 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional research plan: CEZ:AV0Z50380511 Keywords : IN-SITU HYBRIDIZATION * LARGE-SCALE ORGANIZATION * RIBOSOMAL-RNA GENES Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.534, year: 2013

Molecular components and toxicity of the venom of the solitary wasp, Anoplius samariensis

International Nuclear Information System (INIS)

Hisada, Miki; Satake, Honoo; Masuda, Katsuyoshi; Aoyama, Masato; Murata, Kazuya; Shinada, Testuro; Iwashita, Takashi; Ohfune, Yasufumi; Nakajima, Terumi

2005-01-01

The solitary spider wasp, Anoplius samariensis, is known to exhibit a unique long-term, non-lethal paralysis in spiders that it uses as a food source for its larvae. However, neither detailed venom components nor paralytic compounds have ever been characterized. In this study, we examined the components in the low molecular weight fraction of the venom and the paralytic activity of the high molecular weight fraction. The major low molecular weight components of the venom were identified as γ-aminobutyric acid and glutamic acid by micro-liquid chromatography/electrospray ionization mass spectrometry and nuclear magnetic resonance spectrometry analysis. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass analysis revealed that the A. samariensis venom contained the various proteins with weights of 4-100 kDa. A biological assay using Joro spiders (Nephila clavata) clearly showed that the high molecular weight fraction of the venom prepared by ultrafiltration exerted as potent non-lethal long-term paralysis as the whole venom, whereas the low molecular weight fraction was devoid of any paralytic activity. These results indicated that several venomous proteins in the high molecular weight fraction are responsible for the paralytic activity. Furthermore, we determined the primary structure of one component designated As-fr-19, which was a novel multiple-cysteine peptide with high sequence similarity to several sea anemone and snake toxins including dendrotoxins, rather than any insect toxic peptides identified so far. Taken together, our data showed the unprecedented molecular and toxicological profiles of wasp venoms

Analysis of Time Reversible Born-Oppenheimer Molecular Dynamics

Directory of Open Access Journals (Sweden)

Lin Lin

2013-12-01

Full Text Available We analyze the time reversible Born-Oppenheimer molecular dynamics (TRBOMD scheme, which preserves the time reversibility of the Born-Oppenheimer molecular dynamics even with non-convergent self-consistent field iteration. In the linear response regime, we derive the stability condition, as well as the accuracy of TRBOMD for computing physical properties, such as the phonon frequency obtained from the molecular dynamics simulation. We connect and compare TRBOMD with Car-Parrinello molecular dynamics in terms of accuracy and stability. We further discuss the accuracy of TRBOMD beyond the linear response regime for non-equilibrium dynamics of nuclei. Our results are demonstrated through numerical experiments using a simplified one-dimensional model for Kohn-Sham density functional theory.

Response of the seagrass Posidonia oceanica to different light environments: Insights from a combined molecular and photo-physiological study.

Science.gov (United States)

Dattolo, E; Ruocco, M; Brunet, C; Lorenti, M; Lauritano, C; D'Esposito, D; De Luca, P; Sanges, R; Mazzuca, S; Procaccini, G

2014-10-01

Here we investigated mechanisms underlying the acclimation to light in the marine angiosperm Posidonia oceanica, along its bathymetric distribution (at -5 m and -25 m), combining molecular and photo-physiological approaches. Analyses were performed during two seasons, summer and autumn, in a meadow located in the Island of Ischia (Gulf of Naples, Italy), where a genetic distinction between plants growing above and below the summer thermocline was previously revealed. At molecular level, analyses carried out using cDNA-microarray and RT-qPCR, revealed the up-regulation of genes involved in photoacclimation (RuBisCO, ferredoxin, chlorophyll binding proteins), and photoprotection (antioxidant enzymes, xanthophyll-cycle related genes, tocopherol biosynthesis) in the upper stand of the meadow, indicating that shallow plants are under stressful light conditions. However, the lack of photo-damage, indicates the successful activation of defense mechanisms. This conclusion is also supported by several responses at physiological level as the lower antenna size, the higher number of reaction centers and the higher xanthophyll cycle pigment pool, which are common plant responses to high-light adaptation/acclimation. Deep plants, despite the lower available light, seem to be not light-limited, thanks to some shade-adaptation strategies (e.g. higher antenna size, lower Ek values). Furthermore, also at the molecular level there were no signs of stress response, indicating that, although the lower energy available, low-light environments are more favorable for P. oceanica growth. Globally, results of whole transcriptome analysis displayed two distinct gene expression signatures related to depth distribution, reflecting the different light-adaptation strategies adopted by P. oceanica along the depth gradient. This observation, also taking into account the genetic disjunction of clones along the bathymetry, might have important implications for micro-evolutionary processes

Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts.

Science.gov (United States)

Tsujii, Noa; Mikawa, Wakako; Tsujimoto, Emi; Adachi, Toru; Niwa, Atsushi; Ono, Hisae; Shirakawa, Osamu

2017-01-01

Previous neuroimaging studies have revealed frontal and temporal functional abnormalities in patients with major depressive disorder (MDD) and a history of suicidal behavior. However, it is unknown whether multi-channel near-infrared spectroscopy (NIRS) signal changes among individuals with MDD are associated with a history of suicide attempts and a diathesis for suicidal behavior (impulsivity, hopelessness, and aggression). Therefore, we aimed to explore frontotemporal hemodynamic responses in depressed patients with a history of suicide attempts using 52-channel NIRS. We recruited 30 patients with MDD and a history of suicidal behavior (suicide attempters; SAs), 38 patient controls without suicidal behavior (non-attempters; NAs), and 40 healthy controls (HCs) matched by age, gender ratio, and estimated IQ. Regional hemodynamic responses during a verbal fluency task (VFT) were monitored using NIRS. Our results showed that severities of depression, impulsivity, aggression, and hopelessness were similar between SAs and NAs. Both patient groups had significantly reduced activation compared with HCs in the bilateral frontotemporal regions. Post hoc analyses revealed that SAs exhibited a smaller hemodynamic response in the left precentral gyrus than NAs and HCs. Furthermore, the reduced response in the left inferior frontal gyrus was negatively correlated with impulsivity level and hemodynamic responses in the right middle frontal gyrus were negatively associated with hopelessness and aggression in SAs but not in NAs and HCs. Our findings suggest that MDD patients with a history of suicide attempts demonstrate patterns of VFT-induced NIRS signal changes different from those demonstrated by individuals without a history of suicidal behaviors, even in cases where clinical symptoms are similar. NIRS has a relatively high time resolution, which may help visually differentiate SAs from NAs.

Molecular Dynamics Simulation and Statistics Analysis Reveals the Defense Response Mechanism in Plants

Science.gov (United States)

Liu, Zhichao; Zhao, Yunjie; Zeng, Chen; Computational Biophysics Lab Team

As the main protein of the bacterial flagella, flagellin plays an important role in perception and defense response. The newly discovered locus, FLS2, is ubiquitously expressed. FLS2 encodes a putative receptor kinase and shares many homologies with some plant resistance genes and even with some components of immune system of mammals and insects. In Arabidopsis, FLS2 perception is achieved by the recognition of epitope flg22, which induces FLS2 heteromerization with BAK1 and finally the plant immunity. Here we use both analytical methods such as Direct Coupling Analysis (DCA) and Molecular Dynamics (MD) Simulations to get a better understanding of the defense mechanism of FLS2. This may facilitate a redesign of flg22 or de-novo design for desired specificity and potency to extend the immune properties of FLS2 to other important crops and vegetables.

Chemoradiotherapy and molecular biology

International Nuclear Information System (INIS)

Hasegawa, Masatoshi; Mitsuhashi, Norio; Niibe, Hideo

2000-01-01

The current status of chemoradiotherapy was reviewed from the standpoint of molecular biology. Chemoradiotherapy was conducted to achieve systemic tumor control, to intensify the response to irradiation, and to reduce adverse reactions. The mechanisms of the efficacy of chemoradiotherapy were: modification of dose-response relationships, inhibition of tumor cell recovery from sublethal damage or potential lethal damage, effects on cell dynamics and the cell cycle, improvement of blood flow or reoxygenation, recruitment, improvement of drug uptake, increased cell damage. Cell death (necrosis and apoptosis) and cancer-related genes were described, as the essential points, because they are involved in the response to chemoradiotherapy. Cisplatin (platinum compound), 5-fluorouracil, etoposide, and taxoid (paclitaxel, docetaxel) were the principal anticancer agents used for chemoradiotherapy, and they enhanced the effects of irradiation. However, even when good responses or synergism between anticancer drug and radiotherapy was observed in in vitro studies, there was little therapeutic advantage clinically. Data from in vitro and in vivo studies should be collected and systemized, and ''molecular biology in chemotherapy'' that can be applied clinically may become established. (K.H.)

Data warehousing in molecular biology.

Science.gov (United States)

Schönbach, C; Kowalski-Saunders, P; Brusic, V

2000-05-01

In the business and healthcare sectors data warehousing has provided effective solutions for information usage and knowledge discovery from databases. However, data warehousing applications in the biological research and development (R&D) sector are lagging far behind. The fuzziness and complexity of biological data represent a major challenge in data warehousing for molecular biology. By combining experiences in other domains with our findings from building a model database, we have defined the requirements for data warehousing in molecular biology.

Molecular pathogenesis and mechanisms of thyroid cancer

Science.gov (United States)

Xing, Mingzhao

2013-01-01

Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

Molecular mechanisms of renal aging.

Science.gov (United States)

Schmitt, Roland; Melk, Anette

2017-09-01

Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Transferability of molecular markers from major legumes to Lathyrus spp. for their application in mapping and diversity studies.

Science.gov (United States)

Almeida, Nuno Felipe; Trindade Leitão, Susana; Caminero, Constantino; Torres, Ana Maria; Rubiales, Diego; Vaz Patto, Maria Carlota

2014-01-01

Lathyrus cicera L. (chickling pea) and L. sativus L. (grass pea) have great potential among grain legumes due to their adaptability to inauspicious environments, high protein content and resistance to serious diseases. Nevertheless, due to its past underused, further activities are required to exploit this potential and to capitalise on the advances in molecular biology that enable improved Lathyrus spp. breeding programmes. In this study we evaluated the transferability of molecular markers developed for closely related legume species to Lathyrus spp. (Medicago truncatula, pea, lentil, faba bean and lupin) and tested the application of those new molecular tools on Lathyrus mapping and diversity studies. Genomic and expressed sequence tag microsatellite, intron-targeted amplified polymorphic, resistance gene analogue and defence-related gene markers were tested. In total 128 (27.7 %) and 132 (28.6 %) molecular markers were successfully cross-amplified, respectively in L. cicera and L. sativus. In total, the efficiency of transferability from genomic microsatellites was 5 %, and from gene-based markers, 55 %. For L. cicera, three cleaved amplified polymorphic sequence markers and one derived cleaved amplified polymorphic sequence marker based on the cross-amplified markers were also developed. Nine of those molecular markers were suitable for mapping in a L. cicera recombinant inbred line population. From the 17 molecular markers tested for diversity analysis, six (35 %) in L. cicera and seven (41 %) in L. sativus were polymorphic and discriminate well all the L. sativus accessions. Additionally, L. cicera accessions were clearly distinguished from L. sativus accessions. This work revealed a high number of transferable molecular markers to be used in current genomic studies in Lathyrus spp. Although their usefulness was higher on diversity studies, they represent the first steps for future comparative mapping involving these species.

Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

Directory of Open Access Journals (Sweden)

David Cohen

Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

Multidisciplinary molecular diagnostics: the 9th European meeting on molecular diagnostics.

Science.gov (United States)

Loonen, Anne J M; Schuurman, Rob; van den Brule, Adriaan J C

2016-01-01

This report presents a summary of the 9th European Meeting on Molecular Diagnostics held in Noordwijk, The Netherlands, 14-16 October 2015. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans, including infectious disease, oncology, outbreak management, population-based cancer screening, standardization and quality control, chronic diseases and pharmacogenetics. Beyond these different areas, shared values are new technologies and novel technical and clinical applications. Approximately 450 participants, the majority coming from European countries, attended the meeting. Besides high quality scientific presentations, more than 35 diagnostic companies presented their latest innovations, altogether in an informal and inspiring scientific ambience.

A tight-binding model of the transmission probability through a molecular junction; a single molecule vs. a molecular layer

International Nuclear Information System (INIS)

Landau, A.; Nitzan, A.

2006-01-01

Full Text: Molecular electronics, one of the major fields of the current effort in nano-science, may be de ed as the study of electronic behaviors, devices and applications that depend on the properties of matter at the molecular scale. If the miniaturization trend of microelectronic devices is to continue, elements such as transistors and contacts will soon shrink to single molecules. The promise of these new technological breakthroughs has been major driving force in this ld. Moreover, the consideration of molecular systems as electronic devices has raised new fundamental questions. In particular, while traditional quantum chemistry deals with electronically closed systems, we now face problems involving molecular systems that are open to their electronic environment, moreover, function in far from equilibrium situations. A generic molecular junction is made of two electrodes connected by a molecular spacer that takes the form of a molecular chain of varying length or a molecular layer of varying thickness. We use a simple nearest-neighbors tight-biding model with the non-equilibrium Green's function (NEGF) method to investigate and compare between a self-assembled monolayer (SAM), finite molecular layer (FML), and single molecule (SM) chemisorption to a surface of a metal substrate. In addition, we examine the difference in the transmission probability through a SAM, FML and SM sandwiched between two metallic electrodes. Dramatic differences are observed between the SM, FML and SAM density of electronic states and transmission functions. In addition, we analyze the effects of changing different physical parameters such as molecule-substrate interaction, molecule-molecule interactions, etc; interesting effects that pertain to the conduction properties of single molecules and molecular layers are observed. Intriguing results are attained when we investigate the commensurability of the SAM with the metallic surface

Antibody responses to a major Pneumocystis carinii antigen in human immunodeficiency virus-infected patients with and without P. carinii pneumonia

DEFF Research Database (Denmark)

Lundgren, Bettina; Lundgren, Jens Dilling; Nielsen, T

1992-01-01

of pulmonary symptoms. Significantly more patients with P. carinii pneumonia (PCP) had detectable antibodies compared with HIV-infected patients without PCP and with HIV-negative controls (50 [66%] of 76 vs. 18 [34%] of 53 and 7 [35%] of 20, respectively; P less than .001), and the level of antibody response......Antibody responses to a major purified human Pneumocystis carinii surface antigen (gp95) were determined by ELISA in human immunodeficiency virus (HIV)-infected patients. Serum IgG directed against gp95 was measured in 129 consecutive HIV-infected patients who underwent bronchoscopy for evaluation...... response, compared with only 1 (3%) of 31 patients without PCP (P less than .001). This patient had PCP on the basis of clinical criteria, including response to therapy. Thus, despite severe immunosuppression, a proportion of HIV-infected patients with PCP can mount a specific IgG-mediated antibody...

Molecular and physiological responses to titanium dioxide ...

Science.gov (United States)

- Changes in tissue transcriptomes and productivity of Arabidopsis thaliana were investigated during exposure of plants to two widely-used engineered metal oxide nanoparticles, titanium dioxide (nano-titanium) and cerium dioxide (nano-cerium). Microarray analyses confirmed that exposure to either nanoparticle altered the transcriptomes of rosette leaves and roots, with comparatively larger numbers of differentially expressed genes (DEGs) found under nano-titania exposure. Nano-titania induced more DEGs in rosette leaves, whereas roots had more DEGs under nano-ceria exposure. MapMan analyses indicated that while nano-titania up-regulated overall and secondary metabolism in both tissues, metabolic processes under nano-ceria remained mostly unchanged. Gene enrichment analysis indicated that both nanoparticles mainly enriched ontology groups such as responses to stress (abiotic and biotic), and defense responses (pathogens), and responses to endogenous stimuli (hormones). Nano-titania specifically induced genes associated with photosynthesis, whereas nano-ceria induced expression of genes related to activating transcription factors, most notably those belonging to the ethylene responsive element binding protein family. Interestingly, there were also increased numbers of rosette leaves and plant biomass under nano-ceria exposure, but not under nano-titania. Other transcriptomic responses did not clearly relate to responses observed at the organism level. This may b

Transcription analysis of the porcine alveolar macrophage response to Mycoplasma hyopneumoniae.

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Li Bin

Full Text Available Mycoplasma hyopneumoniae is considered the major causative agent of porcine respiratory disease complex, occurs worldwide and causes major economic losses to the pig industry. To gain more insights into the pathogenesis of this organism, the high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages to M. hyopneumoniae infection. A total of 1033 and 1235 differentially expressed genes were identified in porcine alveolar macrophages in responses to exposure to M. hyopneumoniae at 6 and 15 hours post infection, respectively. The differentially expressed genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, cell adhesion, defense response, signal transduction, protein folding, protein ubiquitination and so on. The pathway analysis demonstrated that the most significant pathways were the chemokine signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, nucleotide-binding oligomerization domains (Nod-like receptor signaling pathway and apoptosis signaling pathway. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR. The expression kinetics of chemokines was further analyzed. The present study is the first to document the response of porcine alveolar macrophages to M. hyopneumoniae infection. The data further developed our understanding of the molecular pathogenesis of M. hyopneumoniae.

Transcription analysis of the porcine alveolar macrophage response to Mycoplasma hyopneumoniae.

Science.gov (United States)

Bin, Li; Luping, Du; Bing, Sun; Zhengyu, Yu; Maojun, Liu; Zhixin, Feng; Yanna, Wei; Haiyan, Wang; Guoqing, Shao; Kongwang, He

2014-01-01

Mycoplasma hyopneumoniae is considered the major causative agent of porcine respiratory disease complex, occurs worldwide and causes major economic losses to the pig industry. To gain more insights into the pathogenesis of this organism, the high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages to M. hyopneumoniae infection. A total of 1033 and 1235 differentially expressed genes were identified in porcine alveolar macrophages in responses to exposure to M. hyopneumoniae at 6 and 15 hours post infection, respectively. The differentially expressed genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, cell adhesion, defense response, signal transduction, protein folding, protein ubiquitination and so on. The pathway analysis demonstrated that the most significant pathways were the chemokine signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, nucleotide-binding oligomerization domains (Nod)-like receptor signaling pathway and apoptosis signaling pathway. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR. The expression kinetics of chemokines was further analyzed. The present study is the first to document the response of porcine alveolar macrophages to M. hyopneumoniae infection. The data further developed our understanding of the molecular pathogenesis of M. hyopneumoniae.

Molecular analysis of UAS(E), a cis element containing stress response elements responsible for ethanol induction of the KlADH4 gene of Kluyveromyces lactis.

Science.gov (United States)

Mazzoni, C; Santori, F; Saliola, M; Falcone, C

2000-01-01

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity, which is specifically induced by ethanol and insensitive to glucose repression. In this work, we report the molecular analysis of UAS(E), an element of the KlADH4 promoter which is essential for the induction of KlADH4 in the presence of ethanol. UAS(E) contains five stress response elements (STREs), which have been found in many genes of Saccharomyces cerevisiae involved in the response of cells to conditions of stress. Whereas KlADH4 is not responsive to stress conditions, the STREs present in UAS(E) seem to play a key role in the induction of the gene by ethanol, a situation that has not been observed in the related yeast S. cerevisiae. Gel retardation experiments showed that STREs in the KlADH4 promoter can bind factor(s) under non-inducing conditions. Moreover, we observed that the RAP1 binding site present in UAS(E) binds KlRap1p.

Increased neural response to social rejection in major depression

NARCIS (Netherlands)

Kumar, Poornima; Waiter, Gordon D.; Dubois, Magda; Milders, Maarten; Reid, Ian; Steele, J. Douglas

2017-01-01

Background: Being a part of community is critical for survival and individuals with major depressive disorder (MDD) have a greater sensitivity to interpersonal stress that makes them vulnerable to future episodes. Social rejection is a critical risk factor for depression and it is said to increase

Transcriptome analysis of Crossostephium chinensis provides insight into the molecular basis of salinity stress responses.

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Haiyan Yang

Full Text Available Soil salinization is becoming a limitation to the utilization of ornamental plants worldwide. Crossostephium chinensis (Linnaeus Makino is often cultivated along the southeast coast of China for its desirable ornamental qualities and high salt tolerance. However, little is known about the genomic background of the salt tolerance mechanism in C. chinensis. In the present study, we used Illumina paired-end sequencing to systematically investigate leaf transcriptomes derived from C. chinensis seedlings grown under normal conditions and under salt stress. A total of 105,473,004 bp of reads were assembled into 163,046 unigenes, of which 65,839 (40.38% of the total and 54,342 (33.32% of the total were aligned in Swiss-Prot and Nr protein, respectively. A total of 11,331 (6.95% differentially expressed genes (DEGs were identified among three comparisons, including 2,239 in 'ST3 vs ST0', 5,880 in 'ST9 vs ST3' and 9,718 in 'ST9 vs ST0', and they were generally classified into 26 Gene Ontology terms and 58 Kyoto Encyclopedia of Genes and Genomes (KEGG pathway terms. Many genes encoding important transcription factors (e.g., WRKY, MYB, and AP2/EREBP and proteins involved in starch and sucrose metabolism, arginine and proline metabolism, plant hormone signal transduction, amino acid biosynthesis, plant-pathogen interactions and carbohydrate metabolism, among others, were substantially up-regulated under salt stress. These genes represent important candidates for studying the salt-response mechanism and molecular biology of C. chinensis and its relatives. Our findings provide a genomic sequence resource for functional genetic assignments in C. chinensis. These transcriptome datasets will help elucidate the molecular mechanisms responsible for salt-stress tolerance in C. chinensis and facilitate the breeding of new stress-tolerant cultivars for high-saline areas using this valuable genetic resource.

Glucosinolate metabolites required for an Arabidopsis innate immune response.

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Clay, Nicole K; Adio, Adewale M; Denoux, Carine; Jander, Georg; Ausubel, Frederick M

2009-01-02

The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity and is defined partly by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen-triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen-triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens.

Molecular basis of antifungal drug resistance in yeasts

DEFF Research Database (Denmark)

Morio, Florent; Jensen, Rasmus Hare; Le Pape, Patrice

2017-01-01

Besides inherent differences in in vitro susceptibilities, clinically-relevant yeast species may acquire resistance upon exposure to most antifungal drugs used in the clinic. In recent years, major fundamental research studies have been conducted to improve our understanding of the molecular basis...... of antifungal resistance. This topic is of major interest as antifungal resistance in yeast is clearly evolving and is correlated with clinical failure. This minireview is an overview of the most recent findings about key molecular mechanisms evolving in human pathogenic yeasts, particularly Candida spp......., in the context of antifungal drug resistance. Also included are the methods currently available for in vitro antifungal susceptibility testing and for molecular detection of mutations associated with resistance. Finally, the genetic drivers of antifungal resistance are discussed in light of the spectra...

MAJOR MOLECULAR GENETIC DRIVERS IN SPORADIC PRIMARY HYPERPARATHYROIDISM.

Science.gov (United States)

Arnold, Andrew

2016-01-01

Primary hyperparathyroidism is primarily due to a solitary parathyroid adenoma but multi-gland disease, parathyroid carcinoma, and ectopic parathyroid hormone production can occur. Although primary hyperparathyroidism mostly presents sporadically, strong familial predispositions also exist. Much is known about heritable genetic mutations responsible for these syndromes, including multiple endocrine neoplasia types 1 and 2A, hyperparathyroidism-jaw tumor syndrome, and familial hypocalciuric hypercalcemia. Acquired mutations in common sporadic hyperparathyroidism have also been discovered. Here we focus on the most common and well-established genetic drivers: 1) involvement of the oncogene cyclin D1 in human neoplasia was first established in parathyroid adenomas, followed by recognition of its importance in other tumor types including breast cancer and B-lymphoid malignancy; and 2) somatic mutation of the MEN1 gene, first identified as the source of pathogenic germline mutations in patients with familial endocrinopathies, is found in a substantial fraction of non-familial parathyroid adenomas.

Molecular diffusion in monolayer and submonolayer nitrogen

DEFF Research Database (Denmark)

Hansen, Flemming Yssing; Bruch, Ludwig Walter

2001-01-01

The orientational and translational motions in a monolayer fluid of physisorbed molecular nitrogen are treated using molecular dynamics simulations. Dynamical response functions and several approximations to the coefficient of translational diffusion are determined for adsorption on the basal plane...

Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

Science.gov (United States)

Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

2017-06-22

Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

Molecular and biological hallmarks of ageing.

Science.gov (United States)

Aunan, J R; Watson, M M; Hagland, H R; Søreide, K

2016-01-01

Ageing is the inevitable time-dependent decline in physiological organ function that eventually leads to death. Age is a major risk factor for many of the most common medical conditions, such as cardiovascular disease, cancer, diabetes and Alzheimer's disease. This study reviews currently known hallmarks of ageing and their clinical implications. A literature search of PubMed/MEDLINE was conducted covering the last decade. Average life expectancy has increased dramatically over the past century and is estimated to increase even further. Maximum longevity, however, appears unchanged, suggesting a universal limitation to the human organism. Understanding the underlying molecular processes of ageing and health decline may suggest interventions that, if used at an early age, can prevent, delay, alleviate or even reverse age-related diseases. Hallmarks of ageing can be grouped into three main categories. The primary hallmarks cause damage to cellular functions: genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis. These are followed by antagonistic responses to such damage: deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Finally, integrative hallmarks are possible culprits of the clinical phenotype (stem cell exhaustion and altered intercellular communication), which ultimately contribute to the clinical effects of ageing as seen in physiological loss of reserve, organ decline and reduced function. The sum of these molecular hallmarks produces the clinical picture of the elderly surgical patient: frailty, sarcopenia, anaemia, poor nutrition and a blunted immune response system. Improved understanding of the ageing processes may give rise to new biomarkers of risk or prognosis, novel treatment targets and translational approaches across disciplines that may improve outcomes. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

DDA/TDB liposomes containing soluble Leishmania major antigens induced a mixed Th1/Th2 immune response in BALB/c mice

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Mansure Hojatizade

2017-04-01

Full Text Available Objective(s: Leishmaniasis is a complex parasitic disease that represents a major public health problem. Despite numerous attempts over the past decades, yet there is no effective vaccine against human leishmaniasis probably due to the lack of suitable adjuvants. In this study, a first generation liposomal-based Leishmania vaccine was developed using soluble Leishmania major antigens (SLA and á, Ü-trehalose6, 6'-dibehenat (TDB as an immunostimulatory adjuvant. In this liposome structure, the cationic lipid Dimethyldioctadecylammonium (DDA provides intrinsic adjuvant activity and cholesterol was added as a membrane stabilizer. Liposomes containing SLA were prepared.Materials and Methods: BALB/c mice were subcutaneously (sc immunized with Lip (DDA/TDB/CHOL-SLA+, Lip (DDA/TDB-SLA+, Lip (DDA-SLA+, Lip (DDA/CHOL-SLA+, SLA or Tris-HCl buffer. Immunization was done every two weeks for three weeks. The immunized mice were then challenged sc in the left footpad with 1×106 stationary phase L. major promastigotes (50 ìl, at 2 weeks after last booster injection.Results: mice immunized with any of the liposomal formulations containing SLA (Lip-SLA+, substantially increased footpad swelling and parasite loads of foot and spleen with no significant difference compared to Tris-HCl buffer or SLA alone. Lip-SLA+ formulations induced a mixed Th1/Th2 immune response characterized by IFN-ã and IL-4 production as well as high levels of IgG1 anti-Leishmania antibody. Conclusion: immunization with liposomes containing DDA and/or TDB in combination with SLA induces a mixed Th1/Th2 immune response and is not an appropriate strategy for preferential induction of a Th1 response and protection against leishmaniasis.

Variations in Primary Teachers’ Responses and Development during Three Major Science In- Service Programmes

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Anthony Pell

2011-01-01

Full Text Available This paper reports on how different types of teachers responded to in-service aimed at developing investigative-based science education (IBSE in primary schools, and the extent to which they applied their new skills in the classroom. Common items from evaluation questionnaires allowed data to be combined from three major in-service programmes. Using complete data sets from 120 teachers, cluster analysis enabled three teacher types to be identified: a small group of ‘science unsures’, with low attitude scores and little confidence, who showed no response to the innovation; ‘holistic improvers’, who showed the largest improvement in science teaching confidence; and ‘high level, positive progressives’, who were very positive to science teaching throughout and showed gains in confidence in teaching physics and chemistry, as well as in demonstrating the relevance of science to their pupils. Taking account of these teacher types alongside interviews and observations, nine developmental stages in how teachers apply their new expertise in the classroom and the whole school are suggested. Major factorsinfluencing application in the classroom are the teachers’ initial science knowledge and pedagogical expertise, and motivating feedback to teachers when pupils responded positively to the innovation. Assessing teachers’ initial level of subject knowledge and science pedagogical expertise to inform the approach and amount of in-service provision is important. Subsequent mentoring as well as support from the school principal when teachers first try IBSE with pupils promotes successful implementation in the classroom.

Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans.

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Michelle D Leach

Full Text Available Eukaryotic cells have evolved mechanisms to sense and adapt to dynamic environmental changes. Adaptation to thermal insults, in particular, is essential for their survival. The major fungal pathogen of humans, Candida albicans, is obligately associated with warm-blooded animals and hence occupies thermally buffered niches. Yet during its evolution in the host it has retained a bona fide heat shock response whilst other stress responses have diverged significantly. Furthermore the heat shock response is essential for the virulence of C. albicans. With a view to understanding the relevance of this response to infection we have explored the dynamic regulation of thermal adaptation using an integrative systems biology approach. Our mathematical model of thermal regulation, which has been validated experimentally in C. albicans, describes the dynamic autoregulation of the heat shock transcription factor Hsf1 and the essential chaperone protein Hsp90. We have used this model to show that the thermal adaptation system displays perfect adaptation, that it retains a transient molecular memory, and that Hsf1 is activated during thermal transitions that mimic fever. In addition to providing explanations for the evolutionary conservation of the heat shock response in this pathogen and the relevant of this response to infection, our model provides a platform for the analysis of thermal adaptation in other eukaryotic cells.

B-1 cells modulate the murine macrophage response to Leishmania major infection.

Science.gov (United States)

Arcanjo, Angelica F; Nunes, Marise P; Silva-Junior, Elias B; Leandro, Monique; da Rocha, Juliana Dutra Barbosa; Morrot, Alexandre; Decote-Ricardo, Debora; Freire-de-Lima, Celio Geraldo

2017-05-26

To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major ( L. major ) in vitro . Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE 2 ) were determined using a PGE 2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE 2 -neutralizing drugs inhibited PGE 2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major . We report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major -infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE 2 in supernatants of L. major -infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major -infected macrophages when the B-1 cells were isolated from IL-10 knockout mice. Our results show that elevated levels of PGE 2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell

EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

Science.gov (United States)

Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

2015-01-01

Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine. PMID:22544168

Molecular Recognition in the Colloidal World.

Science.gov (United States)

Elacqua, Elizabeth; Zheng, Xiaolong; Shillingford, Cicely; Liu, Mingzhu; Weck, Marcus

2017-11-21

Colloidal self-assembly is a bottom-up technique to fabricate functional nanomaterials, with paramount interest stemming from programmable assembly of smaller building blocks into dynamic crystalline domains and photonic materials. Multiple established colloidal platforms feature diverse shapes and bonding interactions, while achieving specific orientations along with short- and long-range order. A major impediment to their universal use as building blocks for predesigned architectures is the inability to precisely dictate and control particle functionalization and concomitant reversible self-assembly. Progress in colloidal self-assembly necessitates the development of strategies that endow bonding specificity and directionality within assemblies. Methodologies that emulate molecular and polymeric three-dimensional (3D) architectures feature elements of covalent bonding, while high-fidelity molecular recognition events have been installed to realize responsive reconfigurable assemblies. The emergence of anisotropic 'colloidal molecules', coupled with the ability to site-specifically decorate particle surfaces with supramolecular recognition motifs, has facilitated the formation of superstructures via directional interactions and shape recognition. In this Account, we describe supramolecular assembly routes to drive colloidal particles into precisely assembled architectures or crystalline lattices via directional noncovalent molecular interactions. The design principles are based upon the fabrication of colloidal particles bearing surface-exposed functional groups that can undergo programmable conjugation to install recognition motifs with high fidelity. Modular and versatile by design, our strategy allows for the introduction and integration of molecular recognition principles into the colloidal world. We define noncovalent molecular interactions as site-specific forces that are predictable (i.e., feature selective and controllable complementary bonding partners

Nuclear molecular halo: the ubiquitous occurrence of van der Waals molecular states near threshold in molecular, nuclear and particle physics

International Nuclear Information System (INIS)

Gai, Moshe

1999-01-01

The observation of large E1 strength near threshold in the electromagnetic dissociation of 11 Li poses a fundamental question: Is the large E1 strength due to the threshold or is it due to a low lying E1 state? Such molecular cluster states were observed in 18 O and in several nuclei near the drip line. We discuss the nature of the threshold effect as well as review the situation in Molecular (and Particle Physics) where such Molecular States are observed near the dissociation limit. We suggest that the situation in 11 Li is reminiscent of the argon-benzene molecule where the argon atom is loosely bound by a polarization (van der Waals) mechanism and thus leads to a very extended object lying near the dissociation limit. Such states are also suggested to dominate the structure of mesons [α 0 (980), f 0 (975)] and baryons [λ(1405)] with proposed Kaon molecular structure (Dalitz) near threshold. The inspection of such states throughout Physics allows us to gain insight into this phenomenon and suggest that a new collective Molecular Dipole Degree of Freedom plays a major role in the structure of hadrons (halo nuclei, mesons and baryons), and that quantitative tools such as the E1 Molecular Sum Rule are useful for elucidating the nature of the observed low lying E1 strength in halo nuclei. (author)

Is mechanical dyssynchrony still a major determinant for responses after cardiac resynchronization therapy?

International Nuclear Information System (INIS)

Zhang Qing; Yu Cheuk Man

2011-01-01

The assessment of mechanical dyssynchrony by advanced echocardiographic technologies and its importance in selecting more appropriate candidates for cardiac resynchronization therapy (CRT) have been disputed, after the announcement of the Predictors of Response to CRT (PROSPECT) trial, as the first evidence derived from a multicenter study. However, attempts in this field have never been stopped, as it appears that the fundamental mechanism of CRT is the correction of dyssynchrony where the detection of baseline dyssynchrony is of particular significance. The QRS width provides simple but very limited information. On the other hand, non-invasive imaging tools such as echocardiography have the capacity for more detailed analysis of mechanical dyssynchrony. We reviewed a number of clinical studies published in the post-PROSPECT era, designed to figure out a predictive algorithm where dyssynchrony measure is included, for identifying the most suitable patients before device implantation. From the analysis, mechanical dyssynchrony remains to be a major determinant for clinical outcomes after CRT, although discrepancies have arisen with respect to the single-center nature, echocardiographic methodologies, and relative merit when compared with other predicting factors. (author)

Association study of a brain-derived neurotrophic factor polymorphism and short-term antidepressant response in major depressive disorders

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Lung-Cheng Huang

2008-10-01

Full Text Available Eugene Lin1,7, Po See Chen2,6,7, Lung-Cheng Huang3,4, Sen-Yen Hsu51Vita Genomics, Inc., Wugu Shiang, Taipei, Taiwan; 2Department of Psychiatry, Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Psychiatry, National Taiwan University Hospital Yun-Lin Branch, Taiwan; 4Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Psychiatry, Chi Mei Medical Center, Liouying, Tainan, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Dou-liou Branch, Yunlin, Taiwan; 7These authors contributed equally to this workAbstract: Major depressive disorder (MDD is one of the most common mental disorders worldwide. Single nucleotide polymorphisms (SNPs can be used in clinical association studies to determine the contribution of genes to drug efficacy. A common SNP in the brain-derived neurotrophic factor (BDNF gene, a methionine (Met substitution for valine (Val at codon 66 (Val66Met, is a candidate SNP for influencing antidepressant treatment outcome. In this study, our goal was to determine the relationship between the Val66Met polymorphism in the BDNF gene and the rapid antidepressant response to venlafaxine in a Taiwanese population with MDD. Overall, the BDNF Val66Met polymorphism was found not to be associated with short-term venlafaxine treatment outcome. However, the BDNF Val66Met polymorphism showed a trend to be associated with rapid venlafaxine treatment response in female patients. Future research with independent replication in large sample sizes is needed to confirm the role of the BDNF Val66Met polymorphism identified in this study.Keywords: antidepressant response, brain-derived neurotrophic factor, major depressive disorder, serotonin and norepinephrine reuptake inhibitor, single nucleotide polymorphisms

Participation in a Year-Long CURE Embedded into Major Core Genetics and Cellular and Molecular Biology Laboratory Courses Results in Gains in Foundational Biological Concepts and Experimental Design Skills by Novice Undergraduate Researchers†

Science.gov (United States)

Peteroy-Kelly, Marcy A.; Marcello, Matthew R.; Crispo, Erika; Buraei, Zafir; Strahs, Daniel; Isaacson, Marisa; Jaworski, Leslie; Lopatto, David; Zuzga, David

2017-01-01

This two-year study describes the assessment of student learning gains arising from participation in a year-long curriculum consisting of a classroom undergraduate research experience (CURE) embedded into second-year, major core Genetics and Cellular and Molecular Biology (CMB) laboratory courses. For the first course in our CURE, students used micro-array or RNAseq analyses to identify genes important for environmental stress responses by Saccharomyces cerevisiae. The students were tasked with creating overexpressing mutants of their genes and designing their own original experiments to investigate the functions of those genes using the overexpression and null mutants in the second CURE course. In order to evaluate student learning gains, we employed three validated concept inventories in a pretest/posttest format and compared gains on the posttest versus the pretest with student laboratory final grades. Our results demonstrated that there was a significant correlation between students earning lower grades in the Genetics laboratory for both years of this study and gains on the Genetics Concept Assessment (GCA). We also demonstrated a correlation between students earning lower grades in the Genetics laboratory and gains on the Introductory Molecular and Cell Biology Assessment (IMCA) for year 1 of the study. Students furthermore demonstrated significant gains in identifying the variable properties of experimental subjects when assessed using the Rubric for Experimental (RED) design tool. Results from the administration of the CURE survey support these findings. Our results suggest that a year-long CURE enables lower performing students to experience greater gains in their foundational skills for success in the STEM disciplines. PMID:28904646

Contrasting impacts of ocean acidification and warming on the molecular responses of CO2-resilient oysters.

Science.gov (United States)

Goncalves, Priscila; Thompson, Emma L; Raftos, David A

2017-06-02

This study characterises the molecular processes altered by both elevated CO 2 and increasing temperature in oysters. Differences in resilience of marine organisms against the environmental stressors associated with climate change will have significant implications for the sustainability of coastal ecosystems worldwide. Some evidence suggests that climate change resilience can differ between populations within a species. B2 oysters represent a unique genetic resource because of their capacity to better withstand the impacts of elevated CO 2 at the physiological level, compared to non-selected oysters from the same species (Saccostrea glomerata). Here, we used proteomic and transcriptomic analysis of gill tissue to evaluate whether the differential response of B2 oysters to elevated CO 2 also extends to increased temperature. Substantial and distinctive effects on protein concentrations and gene expression were evident among B2 oysters responding to elevated CO 2 or elevated temperature. The combination of both stressors also altered oyster gill proteomes and gene expression. However, the impacts of elevated CO 2 and temperature were not additive or synergistic, and may be antagonistic. The data suggest that the simultaneous exposure of CO 2 -resilient oysters to near-future projected ocean pH and temperature results in complex changes in molecular processes in order to prevent stress-induced cellular damage. The differential response of B2 oysters to the combined stressors also indicates that the addition of thermal stress may impair the resilience of these oysters to decreased pH. Overall, this study reveals the intracellular mechanisms that might enable marine calcifiers to endure the emergent, adverse seawater conditions resulting from climate change.

The host immune response to Clostridium difficile infection

Science.gov (United States)

2013-01-01

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-acquired diarrhoea. Outcomes of C. difficile colonization are varied, from asymptomatic carriage to fulminant colitis and death, due in part to the interplay between the pathogenic virulence factors of the bacterium and the counteractive immune responses of the host. Secreted toxins A and B are the major virulence factors of C. difficile and induce a profound inflammatory response by intoxicating intestinal epithelial cells causing proinflammatory cytokine release. Host cell necrosis, vascular permeability and neutrophil infiltration lead to an elevated white cell count, profuse diarrhoea and in severe cases, dehydration, hypoalbuminaemia and toxic megacolon. Other bacterial virulence factors, including surface layer proteins and flagella proteins, are detected by host cell surface signal molecules that trigger downstream cell-mediated immune pathways. Human studies have identified a role for serum and faecal immunoglobulin levels in protection from disease, but the recent development of a mouse model of CDI has enabled studies into the precise molecular interactions that trigger the immune response during infection. Key effector molecules have been identified that can drive towards a protective anti-inflammatory response or a damaging proinflammatory response. The limitations of current antimicrobial therapies for CDI have led to the development of both active and passive immunotherapies, none of which have, as yet been formally approved for CDI. However, recent advances in our understanding of the molecular basis of host immune protection against CDI may provide an exciting opportunity for novel therapeutic developments in the future. PMID:25165542

Site-discrimination by molecular imposters at dissymmetric molecular crystal surfaces

Science.gov (United States)

Poloni, Laura N.

The organization of atoms and molecules into crystalline forms is ubiquitous in nature and has been critical to the development of many technologies on which modern society relies. Classical crystal growth theory can describe atomic crystal growth, however, a description of molecular crystal growth is lacking. Molecular crystals are often characterized by anisotropic intermolecular interactions and dissymmetric crystal surfaces with anisotropic growth rates along different crystallographic directions. This thesis describes combination of experimental and computational techniques to relate crystal structure to surface structure and observed growth rates. Molecular imposters, also known as tailor-made impurities, can be used to control crystal growth for practical applications such as inhibition of pathological crystals, but can also be used to understand site specificity at crystal growth surfaces. The first part of this thesis builds on previous real-time in situ atomic force microscopy (AFM) observations of dislocation-actuated growth on the morphologically significant face of hexagonal L-cystine crystals, which aggregate in vivo to form kidney stones in patients suffering from cystinuria. The inhibitory effect of various L-cystine structural mimics (a.k.a. molecular imposters) was investigated through experimental and computational methods to identify the key structural factors responsible for molecular recognition between molecular imposters and L-cystine crystal surface sites. The investigation of L-cystine crystal growth in the presence of molecular imposters through a combination of kinetic analysis using in situ AFM, morphology analysis and birefringence measurements of bulk crystals, and molecular modeling of imposter binding to energetically inequivalent surface sites revealed that different molecular imposters inhibited crystal growth by a Cabrera-Vermilyea pinning mechanism and that imposters bind to a single binding site on the dissymmetric {1000} L

Phenotypical and molecular responses of Arabidopsis thaliana roots as a result of inoculation with the auxin-producing bacterium Azospirillum brasilense.

Science.gov (United States)

Spaepen, Stijn; Bossuyt, Stijn; Engelen, Kristof; Marchal, Kathleen; Vanderleyden, Jos

2014-02-01

The auxin-producing bacterium Azospirillum brasilense Sp245 can promote the growth of several plant species. The model plant Arabidopsis thaliana was chosen as host plant to gain an insight into the molecular mechanisms that govern this interaction. The determination of differential gene expression in Arabidopsis roots after inoculation with either A. brasilense wild-type or an auxin biosynthesis mutant was achieved by microarray analysis. Arabidopsis thaliana inoculation with A. brasilense wild-type increases the number of lateral roots and root hairs, and elevates the internal auxin concentration in the plant. The A. thaliana root transcriptome undergoes extensive changes on A. brasilense inoculation, and the effects are more pronounced at later time points. The wild-type bacterial strain induces changes in hormone- and defense-related genes, as well as in plant cell wall-related genes. The A. brasilense mutant, however, does not elicit these transcriptional changes to the same extent. There are qualitative and quantitative differences between A. thaliana responses to the wild-type A. brasilense strain and the auxin biosynthesis mutant strain, based on both phenotypic and transcriptomic data. This illustrates the major role played by auxin in the Azospirillum-Arabidopsis interaction, and possibly also in other bacterium-plant interactions. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Molecular imaging in patients with mood disorders: a review of PET findings

International Nuclear Information System (INIS)

Chen, Qiaozhen; Liu, Weibo; Li, Huichun; Zhang, Hong; Tian, Mei

2011-01-01

Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

Molecular imaging in patients with mood disorders: a review of PET findings

Energy Technology Data Exchange (ETDEWEB)

Chen, Qiaozhen [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Liu, Weibo; Li, Huichun [Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhang, Hong [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [The University of Texas MD Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

2011-07-15

Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

Molecular Imaging and Precision Medicine in Lung Cancer.

Science.gov (United States)

Zukotynski, Katherine A; Gerbaudo, Victor H

2017-01-01

Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Chronic myelogenous leukemia: molecular monitoring in clinical practice

Directory of Open Access Journals (Sweden)

N. R. Ryabchikova

2013-01-01

Full Text Available Use of tyrosine kinase inhibitor imatinib has led to significant progress in chronic myeloid leukemia (CML treatment. To date, genetic monitoring is a mandatory attribute of therapy with tyrosine kinase inhibitors. The purpose of this study was to access the imatinib therapy efficacy in CML patients using complete molecular genetic monitoring by standard cytogenetics, realtime polymerase chain reaction and mutational analysis. Correlation between cytogenetic and molecular response was shown. Heterogeneity of molecular response in each patient group was revealed by expression of BCR-ABL. Kinase domain mutations were detected in 32 % of CML patients resistant to imatinib.

A molecular spin-photovoltaic device.

Science.gov (United States)

Sun, Xiangnan; Vélez, Saül; Atxabal, Ainhoa; Bedoya-Pinto, Amilcar; Parui, Subir; Zhu, Xiangwei; Llopis, Roger; Casanova, Fèlix; Hueso, Luis E

2017-08-18

We fabricated a C 60 fullerene-based molecular spin-photovoltaic device that integrates a photovoltaic response with the spin transport across the molecular layer. The photovoltaic response can be modified under the application of a small magnetic field, with a magnetophotovoltage of up to 5% at room temperature. Device functionalities include a magnetic current inverter and the presence of diverging magnetocurrent at certain illumination levels that could be useful for sensing. Completely spin-polarized currents can be created by balancing the external partially spin-polarized injection with the photogenerated carriers. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The molecular basis of peanut allergy

Science.gov (United States)

Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures, and discusses how modif...

Development of haplotype-specific molecular markers for the low-molecular-weight glutenin subunits

Science.gov (United States)

Low-molecular-weight glutenin subunits (LMW-GSs) are one of the major components of gluten and their allelic variation has been widely associated with numerous wheat end-use quality parameters. These proteins are encoded by multigene families located at the orthologous Glu-3 loci (Glu-A3, Glu-B3 and...

Membrane Lipid Oscillation: An Emerging System of Molecular Dynamics in the Plant Membrane.

Science.gov (United States)

Nakamura, Yuki

2018-03-01

Biological rhythm represents a major biological process of living organisms. However, rhythmic oscillation of membrane lipid content is poorly described in plants. The development of lipidomic technology has led to the illustration of precise molecular profiles of membrane lipids under various growth conditions. Compared with conventional lipid signaling, which produces unpredictable lipid changes in response to ever-changing environmental conditions, lipid oscillation generates a fairly predictable lipid profile, adding a new layer of biological function to the membrane system and possible cross-talk with the other chronobiological processes. This mini review covers recent studies elucidating membrane lipid oscillation in plants.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

Science.gov (United States)

García-Gutiérrez, Valentin; Puerta, Jose Manuel; Maestro, Begoña; Casado Montero, Luis Felipe; Muriel, Alfonso; Molina Hurtado, Jose Ramon; Perez-Encinas, Manuel; Moreno Romero, Maria Victoria; Suñol, Pere Barba; Sola Garcia, Ricardo; De Paz, Raquel; Ramirez Sanchez, Maria Jose; Osorio, Santiago; Mata Vazquez, Maria Isabel; Martinez López, Joaquin; Sastre, Jose Luis; Portero, Maria de Los Angles; Bautista, Guiomar; Duran Nieto, Maria Soledad; Giraldo, Pilar; Jimenez Jambrina, Margarita; Burgaleta, Carmen; Ruiz Aredondo, Joaquin; Peñarrubia, Maria Jesús; Requena, Maria José; Fernández Valle, María Del Carmen; Calle, Carmen; Paz Coll, Antonio; Hernández-Rivas, Jose Ángel; Franco Osorio, Rafael; Cano, Pilar; Tallón Pérez, David; Fernández de la Mata, Margarita; Garrido, Pilar López; Steegmann, Juan Luis

2014-11-01

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival. © 2014 Wiley Periodicals, Inc.

Vitamin D and Colorectal Cancer: Molecular, Epidemiological, and Clinical Evidence

Science.gov (United States)

Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L.; Manson, JoAnn E.; Qian, Zhi Rong; Ogino, Shuji

2016-01-01

In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

Science.gov (United States)

Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

2016-05-01

In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

Molecular Diagnostic Tests for Microsporidia

Directory of Open Access Journals (Sweden)

Kaya Ghosh

2009-01-01

Full Text Available The Microsporidia are a ubiquitous group of eukaryotic obligate intracellular parasites which were recognized over 100 years ago with the description of Nosema bombycis, a parasite of silkworms. It is now appreciated that these organisms are related to the Fungi. Microsporidia infect all major animal groups most often as gastrointestinal pathogens; however they have been reported from every tissue and organ, and their spores are common in environmental sources such as ditch water. Several different genera of these organisms infect humans, but the majority of infections are due to either Enterocytozoon bieneusi or Encephalitozoon species. These pathogens can be difficult to diagnose, but significant progress has been made in the last decade in the development of molecular diagnostic reagents for these organisms. This report reviews the molecular diagnostic tests that have been described for the identification of the microsporidia that infect humans.

Social responsibilities of a physician: reflections of Major General S L Bhatia (1891-1981).

Science.gov (United States)

Hegde, Radhika; Vaz, Mario

2017-01-01

This paper examines various documents written by Major General SL Bhatia CIE, MC, IMS from the 1920s to the1960s on the "Social Responsibilities of a Physician". His reflections are of historical significance, since they provide us with an insight into the challenges confronting the people who attempted to rebuild a nation plagued by poverty resulting from fractured agricultural growth, a feudalistic social structure and the regional inequalities that accompany it, and prolonged imperial rule, among other things. Bhatia's thoughts, especially on medical education and the condition of rural health and sanitation, enable us to understand India's present health concerns through the prism of the past. The writings of Bhatia, who lived during a period of transition in India, reflect an understanding of health issues from the perspectives both of an administrator and a physician struggling to meet the challenges of a nascent nation. He insisted on rooting his medical teachings in the principles of the humanities and ethics.

Perception of Global Climate Change as a Mediator of the Effects of Major and Religious Affiliation on College Students' Environmentally Responsible Behavior

Science.gov (United States)

Fusco, Emily; Snider, Anthony; Luo, Shanhong

2012-01-01

Previous research has shown a reliable association between environmental education and environmentally responsible behavior (ERB). Research has also shown that aspects of religion were associated with ERB. However, the mechanisms of associations are unclear. This study builds on previous research addressing the relationship between student major,…

Sirtuins: Molecular Traffic Lights in the Crossroad of Oxidative Stress, Chromatin Remodeling, and Transcription

Directory of Open Access Journals (Sweden)

Ramkumar Rajendran

2011-01-01

Full Text Available Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+ (nicotinamide adenine dinucleotide, and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper.

Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response*

Science.gov (United States)

Clay, Nicole K.; Adio, Adewale M.; Denoux, Carine; Jander, Georg; Ausubel, Frederick M.

2008-01-01

Summary The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity, and is defined in part by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens. PMID:19095898

Existence of Inverted Profile in Chemically Responsive Molecular Pathways in the Zebrafish Liver

Science.gov (United States)

Zhang, Xun; Li, Hu; Ma, Jing; Zhang, Louxin; Li, Baowen; Gong, Zhiyuan

2011-01-01

How a living organism maintains its healthy equilibrium in response to endless exposure of potentially harmful chemicals is an important question in current biology. By transcriptomic analysis of zebrafish livers treated by various chemicals, we defined hubs as molecular pathways that are frequently perturbed by chemicals and have high degree of functional connectivity to other pathways. Our network analysis revealed that these hubs were organized into two groups showing inverted functionality with each other. Intriguingly, the inverted activity profiles in these two groups of hubs were observed to associate only with toxicopathological states but not with physiological changes. Furthermore, these inverted profiles were also present in rat, mouse, and human under certain toxicopathological conditions. Thus, toxicopathological-associated anti-correlated profiles in hubs not only indicate their potential use in diagnosis but also development of systems-based therapeutics to modulate gene expression by chemical approach in order to rewire the deregulated activities of hubs back to normal physiology. PMID:22140468

Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway.

Directory of Open Access Journals (Sweden)

Hongjie Zhu

Full Text Available Therapeutic response to selective serotonin (5-HT reuptake inhibitors in Major Depressive Disorder (MDD varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35 or placebo (n = 40 in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17. Targeted electrochemistry based metabolomic platform (LCECA was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ(2(1  = 0.75, p = 0.39. Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM, greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL and Melatonin (MEL levels, and decreases in the (KYN/MEL and 3-Hydroxykynurenine (3-OHKY/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for

Progress in molecular precursors for electronic materials

Energy Technology Data Exchange (ETDEWEB)

Buhro, W.E. [Washington Univ., St. Louis, MO (United States)

1996-09-01

Molecular-precursor chemistry provides an essential underpinning to all electronic-materials technologies, including photovoltaics and related areas of direct interest to the DOE. Materials synthesis and processing is a rapidly developing field in which advances in molecular precursors are playing a major role. This article surveys selected recent research examples that define the exciting current directions in molecular-precursor science. These directions include growth of increasingly complex structures and stoichiometries, surface-selective growth, kinetic growth of metastable materials, growth of size-controlled quantum dots and quantum-dot arrays, and growth at progressively lower temperatures. Continued progress in molecular-precursor chemistry will afford precise control over the crystal structures, nanostructures, and microstructures of electronic materials.

Molecular Electronics of Self-Assembled Monolayers

DEFF Research Database (Denmark)

Wang, Xintai

This thesis deals withmolecular electronic investigations on self-assembledmonolayers. The thesis is divided into seven chapters, as outlined below.Chapter 1 is a general introduction of the history of molecular electronics and its current state.Chapter 2 is separated into three parts. Part I...... providesa brief introduction toself-assembledmonolayers(SAMs), includingits structure, formation, and its role in molecular electronic investigations. Part II is an introduction of different molecular functions, which are interesting for designing real devices. Part III is an introduction of a novel carbon...... material: graphene, and how such material can be incorporated intothe field of molecular electronics.Chapter 3 is a brief introduction of important instruments used in this thesis.Chapter 4, 5 and 6 describe the major experimental work in this thesis. Chapter 4 introduces two novel anchoring...

An outbreak of Leishmania major from an endemic to a non-endemic region posed a public health threat in Iraq from 2014-2017: Epidemiological, molecular and phylogenetic studies.

Directory of Open Access Journals (Sweden)

Mariwan M M Al-Bajalan

2018-03-01

Full Text Available Cutaneous leishmaniasis (CL is a neglected worldwide, zoonotic, vector-borne, tropical disease that is a threat to public health. This threat may spread from endemic to non-endemic areas. Current research has exploited epidemiological, molecular and phylogenetical studies to determine the danger of an outbreak of CL in the borderline area between northern and central Iraq from 2014-2017.For the first time, using sequence analysis of the cytochrome b gene, the occurrence of CL in the borderline area between northern and central Iraq was confirmed to be due to Leishmania major. The phylogenetic analysis indicated that it was closely related to the L. major MRHO/IR/75/ER strain in Iran.In conclusion, the genotype confirmation of the L. major strain will improve our understanding of the epidemiology of the disease. This is important for facilitating control programs to prevent the further spread of CL. Furthermore, this area could be considered as a model for further research on the risk of global CL epidemics in other non-endemic countries where both reservoir hosts and sandfly vectors are present.

An outbreak of Leishmania major from an endemic to a non-endemic region posed a public health threat in Iraq from 2014-2017: Epidemiological, molecular and phylogenetic studies.

Science.gov (United States)

Al-Bajalan, Mariwan M M; Al-Jaf, Sirwan M A; Niranji, Sherko S; Abdulkareem, Dler R; Al-Kayali, Khudhair K; Kato, Hirotomo

2018-03-01

Cutaneous leishmaniasis (CL) is a neglected worldwide, zoonotic, vector-borne, tropical disease that is a threat to public health. This threat may spread from endemic to non-endemic areas. Current research has exploited epidemiological, molecular and phylogenetical studies to determine the danger of an outbreak of CL in the borderline area between northern and central Iraq from 2014-2017. For the first time, using sequence analysis of the cytochrome b gene, the occurrence of CL in the borderline area between northern and central Iraq was confirmed to be due to Leishmania major. The phylogenetic analysis indicated that it was closely related to the L. major MRHO/IR/75/ER strain in Iran. In conclusion, the genotype confirmation of the L. major strain will improve our understanding of the epidemiology of the disease. This is important for facilitating control programs to prevent the further spread of CL. Furthermore, this area could be considered as a model for further research on the risk of global CL epidemics in other non-endemic countries where both reservoir hosts and sandfly vectors are present.

Advancing the education in molecular diagnostics: the IFCC-Initiative "Clinical Molecular Biology Curriculum" (C-CMBC); a ten-year experience.

Science.gov (United States)

Lianidou, Evi; Ahmad-Nejad, Parviz; Ferreira-Gonzalez, Andrea; Izuhara, Kenji; Cremonesi, Laura; Schroeder, Maria-Eugenia; Richter, Karin; Ferrari, Maurizio; Neumaier, Michael

2014-09-25

Molecular techniques are becoming commonplace in the diagnostic laboratory. Their applications influence all major phases of laboratory medicine including predisposition/genetic risk, primary diagnosis, therapy stratification and prognosis. Readily available laboratory hardware and wetware (i.e. consumables and reagents) foster rapid dissemination to countries that are just establishing molecular testing programs. Appropriate skill levels extending beyond the technical procedure are required for analytical and diagnostic proficiency that is mandatory in molecular genetic testing. An international committee (C-CMBC) of the International Federation for Clinical Chemistry (IFCC) was established to disseminate skills in molecular genetic testing in member countries embarking on the respective techniques. We report the ten-year experience with different teaching and workshop formats for beginners in molecular diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

Asymmetric Response toward Molecular Fluorination in Binary Copper–Phthalocyanine/Pentacene Assemblies

DEFF Research Database (Denmark)

de Oteyza, D. G.; García Lastra, Juan Maria; Goiri, E.

2014-01-01

We report a didactic and simple example of the subtleness in the balance of intermolecular and molecule–substrate interactions and its effect on molecular self-assembly. The study is performed on two closely related molecular blends of copper phthalocyanines and pentacene, in each of which one of...... intermolecular interactions and a larger corrugation in the molecule–substrate interaction potential, results in a disordered layer. However, the difference between the two blend’s structures vanishes when substrates with less corrugated interaction potentials are used....

Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout

International Nuclear Information System (INIS)

Burki, Richard; Krasnov, Aleksei; Bettge, Kathrin; Rexroad, Caird E.; Afanasyev, Sergey; Antikainen, Miia; Burkhardt-Holm, Patricia; Wahli, Thomas; Segner, Helmut

2013-01-01

The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors. The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17β-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment. Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades. Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors. More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors. Organism-level responses to concurrent E2 and parasite treatment – assessed through measuring parasite loads in the fish host and cumulative mortalities of trout – were dominated by the pathogen, with no modulating influence of E2. The findings reveal function- and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.

Molecular crosstalk between a chemical and a biological stressor and consequences on disease manifestation in rainbow trout

Energy Technology Data Exchange (ETDEWEB)

Burki, Richard [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Krasnov, Aleksei [NOFIMA Marin, Postboks. 5010, 1432As (Norway); Bettge, Kathrin [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Rexroad, Caird E. [National Center for Cool and Cold Water Aquaculture, USDA-ARS, 11876 Leetown Road, Kearneysville, WV 25430 (United States); Afanasyev, Sergey [Sechenov Institute of Evolutionary Physiology and Biochemistry, M. Toreza av. 44, Peterburg 194223 (Russian Federation); Antikainen, Miia [Institute of Applied Biotechnology, University of Kuopio (Finland); Burkhardt-Holm, Patricia [Man-Society-Environment, University of Basel, Vesalgasse 1, CH-4051 Basel (Switzerland); Wahli, Thomas [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland); Segner, Helmut, E-mail: helmut.segner@vetsuisse.unibe.ch [Centre for Fish and Wildlife Health, University of Bern, Laenggassstrasse 122, CH-3001 Bern (Switzerland)

2013-02-15

The aim of the present study was to examine the molecular and organism reaction of rainbow trout, Oncorhynchus mykiss, to the combined impact of two environmental stressors. The two stressors were the myxozoan parasite, Tetracapsuloides bryosalmonae, which is the etiological agent of proliferative kidney disease (PKD) and a natural stressor to salmonid populations, and 17{beta}-estradiol (E2) as prototype of estrogen-active chemical stressors in the aquatic environment. Both stressors, the parasite and estrogenic contaminants, co-exist in Swiss rivers and are discussed as factors contributing to the decline of Swiss brown trout populations over the last decades. Using a microarray approach contrasting parasite-infected and non-infected rainbow trout at low or high estrogen levels, it was observed that molecular response patterns under joint exposure differed from those to the single stressors. More specifically, three major response patterns were present: (i) expression responses of gene transcripts to one stressor are weakened by the presence of the second stressor; (ii) expression responses of gene transcripts to one stressor are enhanced by the presence of the second stressor; (iii) expression responses of gene transcripts at joint treatment are dominated by one of the two stressors. Organism-level responses to concurrent E2 and parasite treatment - assessed through measuring parasite loads in the fish host and cumulative mortalities of trout - were dominated by the pathogen, with no modulating influence of E2. The findings reveal function- and level-specific responses of rainbow trout to stressor combinations, which are only partly predictable from the response to the single stressors.

The molecular hydrogen explorer H2EX

NARCIS (Netherlands)

Boulanger, F.; Maillard, J. P.; Appleton, P.; Falgarone, E.; Lagache, G.; Schulz, B.; Wakker, B. P.; Bressan, A.; Cernicharo, J.; Charmandaris, V.; Drissen, L.; Helou, G.; Henning, T.; Lim, T. L.; Valentjin, E. A.; Abergel, A.; Bourlot, J. Le; Bouzit, M.; Cabrit, S.; Combes, F.; Deharveng, J. M.; Desmet, P.; Dole, H.; Dumesnil, C.; Dutrey, A.; Fourmond, J. J.; Gavila, E.; Grangé, R.; Gry, C.; Guillard, P.; Guilloteau, S.; Habart, E.; Huet, B.; Joblin, C.; Langer, M.; Longval, Y.; Madden, S. C.; Martin, C.; Miville-Deschênes, M. A.; Pineau Des Forêts, G.; Pointecouteau, E.; Roussel, H.; Tresse, L.; Verstraete, L.; Viallefond, F.; Bertoldi, F.; Jorgensen, J.; Bouwman, J.; Carmona, A.; Krause, O.; Baruffolo, A.; Bonoli, C.; Bortoletto, F.; Danese, L.; Granato, G. L.; Pernechele, C.; Rampazzo, R.; Silva, L.; Zotti, G. De; Pardo, J.; Spaans, M.; van der Tak, F. F. S.; Wild, W.; Ferlet, M. J.; Ramsay Howat, S. K.; Smith, M. D.; Swinyard, B.; Wright, G. S.; Joncas, G.; Martin, P. G.; Davis, C. J.; Draine, B. T.; Goldsmith, P. F.; Mainzer, A. K.; Ogle, P.; Rinehart, S. A.; Stacey, G. J.; Tielens, A. G. G. M.

The Molecular Hydrogen Explorer, H2 EX, was proposed in response to the ESA 2015 - 2025 Cosmic Vision Call as a medium class space mission with NASA and CSA participations. The mission, conceived to understand the formation of galaxies, stars and planets from molecular hydrogen, is designed to

A machine learning approach using EEG data to predict response to SSRI treatment for major depressive disorder.

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Khodayari-Rostamabad, Ahmad; Reilly, James P; Hasey, Gary M; de Bruin, Hubert; Maccrimmon, Duncan J

2013-10-01

The problem of identifying, in advance, the most effective treatment agent for various psychiatric conditions remains an elusive goal. To address this challenge, we investigate the performance of the proposed machine learning (ML) methodology (based on the pre-treatment electroencephalogram (EEG)) for prediction of response to treatment with a selective serotonin reuptake inhibitor (SSRI) medication in subjects suffering from major depressive disorder (MDD). A relatively small number of most discriminating features are selected from a large group of candidate features extracted from the subject's pre-treatment EEG, using a machine learning procedure for feature selection. The selected features are fed into a classifier, which was realized as a mixture of factor analysis (MFA) model, whose output is the predicted response in the form of a likelihood value. This likelihood indicates the extent to which the subject belongs to the responder vs. non-responder classes. The overall method was evaluated using a "leave-n-out" randomized permutation cross-validation procedure. A list of discriminating EEG biomarkers (features) was found. The specificity of the proposed method is 80.9% while sensitivity is 94.9%, for an overall prediction accuracy of 87.9%. There is a 98.76% confidence that the estimated prediction rate is within the interval [75%, 100%]. These results indicate that the proposed ML method holds considerable promise in predicting the efficacy of SSRI antidepressant therapy for MDD, based on a simple and cost-effective pre-treatment EEG. The proposed approach offers the potential to improve the treatment of major depression and to reduce health care costs. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

MOLECULAR DIAGNOSTICS - ANOTHER PIECE IN THE ENVIRONMENTAL PUZZLE

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Molecular biology offers sensitive and expedient tools for the detection of exposure to environmental stressors. Molecular approaches provide the means for detection of the "first cellular event(s)" in response to environmental changes-specifically, immediate changes in gene expr...

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Science.gov (United States)

Steegmann, Juan Luis; Colomer, Dolors; Gómez-Casares, Maria-Teresa; García-Gutiérrez, Valentín; Ortí, Guillermo; Ramírez-Payer, Angel; Olavarria, Eduardo; Vall-Llovera, Ferrán; Giraldo, Pilar; Conde, Eulogio; Vallansot, Rolando; López-Lorenzo, Jose Luis; Palomera, Luis; Álvarez-Larrán, Alberto; Conesa, Venancio; Bautista, Guiomar; Casas, Laura; Giles, Frank; Hochhaus, Andreas; Casado-Montero, Luis Felipe

2017-10-01

This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

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Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

2016-01-01

Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

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Govindarajan Kunde R

2011-05-01

Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

Stress response and communication in surgeons undergoing training in endoscopic management of major vessel hemorrhage: a mixed methods study.

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Jukes, Alistair K; Mascarenhas, Annika; Murphy, Jae; Stepan, Lia; Muñoz, Tamara N; Callejas, Claudio A; Valentine, Rowan; Wormald, P J; Psaltis, Alkis J

2017-06-01

Major vessel hemorrhage in endoscopic, endonasal skull-base surgery is a rare but potentially fatal event. Surgical simulation models have been developed to train surgeons in the techniques required to manage this complication. This mixed-methods study aims to quantify the stress responses the model induces, determine how realistic the experience is, and how it changes the confidence levels of surgeons in their ability to deal with major vascular injury in an endoscopic setting. Forty consultant surgeons and surgeons in training underwent training on an endoscopic sheep model of jugular vein and carotid artery injury. Pre-course and post-course questionnaires providing demographics, experience level, confidence, and realism scores were taken, based on a 5-point Likert scale. Objective markers of stress response including blood pressure, heart rate, and salivary alpha-amylase levels were measured. Mean "realism" score assessed posttraining showed the model to be perceived as highly realistic by the participants (score 4.02). Difference in participant self-rated pre-course and post-course confidence levels was significant (p confidence level 1.66 (95% confidence interval [CI], 1.43 to 1.90); mean post-course confidence level 3.42 (95% CI, 3.19 to 3.65). Differences in subjects' heart rates (HRs) and mean arterial blood pressures (MAPs) were significant between injury models (p = 0.0008, p = 0.0387, respectively). No statistically significant difference in salivary alpha-amylase levels pretraining and posttraining was observed. Results from this study indicate that this highly realistic simulation model provides surgeons with an increased level of confidence in their ability to deal with the rare but potentially catastrophic event of major vessel injury in endoscopic skull-base surgery. © 2017 ARS-AAOA, LLC.

A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.

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Aquea, Felipe; Federici, Fernan; Moscoso, Cristian; Vega, Andrea; Jullian, Pastor; Haseloff, Jim; Arce-Johnson, Patricio

2012-04-01

Boron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We show that application of BA reduces the size of root meristems, correlating with the inhibition of root growth. The decrease in meristem size is caused by a reduction of cell division. Mitotic cell number significantly decreases and the expression level of key core cell cycle regulators is modulated. The modulation of the cell cycle does not appear to act through cytokinin and auxin signalling. A global expression analysis reveals that boron toxicity induces the expression of genes related with abscisic acid (ABA) signalling, ABA response and cell wall modifications, and represses genes that code for water transporters. These results suggest that boron toxicity produces a reduction of water and BA uptake, triggering a hydric stress response that produces root growth inhibition. © 2011 Blackwell Publishing Ltd.

Effect of Irradiation on the Mixture of Egg White Proteins Responsible for Foaming Property

International Nuclear Information System (INIS)

Xian De Liu; Rong Xiu Han; Dong-Il Jin; Soo-Kee Lee; Cheo-Run Jo

2009-01-01

Irradiation of egg white increased foaming ability significantly. To investigate the protein modification by irradiation responsible for the increase of foaming ability, 3 major egg white proteins were purchased and mixed (7.7 g/L ovalbumin, 1.8 g/L ovotransferrin, 0.5 g/L lysozyme) as a model system and irradiated at 0, 2.5, and 5 kGy. The different protein expressions were evaluated using 2-D electrophoresis and it was found that ovotransferrin was cleaved by irradiation and molecular weight and isoelectric point were changed. In addition, many uncharacterized proteins were found and it indicated that irradiation modified proteins randomly but mainly fragmentation was observed. Therefore, it can be concluded that protein fragmentation of 3 major egg white proteins responsible for foaming ability may be the main reason for the improvement of foaming ability

Organization of a radioisotope based molecular biology laboratory

International Nuclear Information System (INIS)

2006-12-01

-isotopes: they often have concerns related to safety. Member States have repeatedly requested help for training when first establishing radioactive-based molecular biology laboratories in particular in radiosafety and quality assurance. The current TECDOC has been prepared in response to these requests and requirements. It represents one of the IAEA's many efforts to contribute with the worldwide implementation of these techniques, and to be a relevant source of information to be used by molecular scientists, major national research institutions, laboratory workers and national health institutions authorities

Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects.

NARCIS (Netherlands)

Fachiroh, J.; Schouten, T; Hariwiyanto, B; Paramita, D.K.; Harijadi, A; Haryana, SM; Ng, MH; Middeldorp, J.M.

2004-01-01

Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal

Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine.

Science.gov (United States)

Lambers Heerspink, Hiddo J; Oberbauer, Rainer; Perco, Paul; Heinzel, Andreas; Heinze, Georg; Mayer, Gert; Mayer, Bernd

2015-08-01

Diabetic kidney disease (DKD) is a complex, multifactorial disease and is associated with a high risk of renal and cardiovascular morbidity and mortality. Clinical practice guidelines for diabetes recommend essentially identical treatments for all patients without taking into account how the individual responds to the instituted therapy. Yet, individuals vary widely in how they respond to medications and therefore optimal therapy differs between individuals. Understanding the underlying molecular mechanisms of variability in drug response will help tailor optimal therapy. Polymorphisms in genes related to drug pharmacokinetics have been used to explore mechanisms of response variability in DKD, but with limited success. The complex interaction between genetic make-up and environmental factors on the abundance of proteins and metabolites renders pharmacogenomics alone insufficient to fully capture response variability. A complementary approach is to attribute drug response variability to individual variability in underlying molecular mechanisms involved in the progression of disease. The interplay of different processes (e.g. inflammation, fibrosis, angiogenesis, oxidative stress) appears to drive disease progression, but the individual contribution of each process varies. Drugs at the other hand address specific targets and thereby interfere in certain disease-associated processes. At this level, biomarkers may help to gain insight into which specific pathophysiological processes are involved in an individual followed by a rational assessment whether a specific drug's mode of action indeed targets the relevant process at hand. This article describes the conceptual background and data-driven workflow developed by the SysKid consortium aimed at improving characterization of the molecular mechanisms underlying DKD at the interference of the molecular impact of individual drugs in order to tailor optimal therapy to individual patients. © The Author 2015. Published by

Comparative study of the protein profiles of Sunki mandarin and Rangpur lime plants in response to water deficit.

Science.gov (United States)

Oliveira, Tahise M; da Silva, Fernanda R; Bonatto, Diego; Neves, Diana M; Morillon, Raphael; Maserti, Bianca E; Filho, Mauricio A Coelho; Costa, Marcio G C; Pirovani, Carlos P; Gesteira, Abelmon S

2015-03-03

Rootstocks play a major role in the tolerance of citrus plants to water deficit by controlling and adjusting the water supply to meet the transpiration demand of the shoots. Alterations in protein abundance in citrus roots are crucial for plant adaptation to water deficit. We performed two-dimensional electrophoresis (2-DE) separation followed by LC/MS/MS to assess the proteome responses of the roots of two citrus rootstocks, Rangpur lime (Citrus limonia Osbeck) and 'Sunki Maravilha' (Citrus sunki) mandarin, which show contrasting tolerances to water deficits at the physiological and molecular levels. Changes in the abundance of 36 and 38 proteins in Rangpur lime and 'Sunki Maravilha' mandarin, respectively, were observed via LC/MS/MS in response to water deficit. Multivariate principal component analysis (PCA) of the data revealed major changes in the protein profile of 'Sunki Maravilha' in response to water deficit. Additionally, proteomics and systems biology analyses allowed for the general elucidation of the major mechanisms associated with the differential responses to water deficit of both varieties. The defense mechanisms of Rangpur lime included changes in the metabolism of carbohydrates and amino acids as well as in the activation of reactive oxygen species (ROS) detoxification and in the levels of proteins involved in water stress defense. In contrast, the adaptation of 'Sunki Maravilha' to stress was aided by the activation of DNA repair and processing proteins. Our study reveals that the levels of a number of proteins involved in various cellular pathways are affected during water deficit in the roots of citrus plants. The results show that acclimatization to water deficit involves specific responses in Rangpur lime and 'Sunki Maravilha' mandarin. This study provides insights into the effects of drought on the abundance of proteins in the roots of two varieties of citrus rootstocks. In addition, this work allows for a better understanding of the

Can short-term administration of dexamethasone abrogate radiation-induced acute cytokine gene response in lung and modify subsequent molecular responses?

International Nuclear Information System (INIS)

Hong, J.-H.; Chiang, C.-S.; Tsao, C.-Y.; Lin, P.-Y.; Wu, C.-J.; McBride, William H.

2001-01-01

Purpose: To investigate the effects of short-term administration of dexamethasone (DEX) on radiation-induced responses in the mouse lung, focusing on expression of pro-inflammatory cytokine and related genes. Methods and Materials: At indicated times after thoracic irradiation and/or drug treatment, mRNA expression levels of cytokines (mTNF-α, mIL-1α, mIL-1β, mIL-2, mIL-3, mIL-4, mIL-5, mIL-6, mIFN-γ) and related genes in the lungs of C3H/HeN mice were measured by RNase protection assay. Results: Radiation-induced pro-inflammatory cytokine mRNA expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg) suppresses both basal cytokine mRNA levels and this early response when given immediately after irradiation. However, by 24 h, in mice treated with DEX alone or DEX plus radiation, there was a strong rebound effect that lasted up to 3 days. Modification of the early radiation-induced response by DEX did not change the second wave of cytokine gene expression in the lung that occurs at 1 to 2 weeks, suggesting that early cytokine gene induction might not determine subsequent molecular events. A single dose of DEX attenuated, but did not completely suppress, increases in cytokine mRNA levels induced by lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no significant rebound effect was seen. Five days of dexamethasone treatment in the pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and, again, there was a rebound effect after withdrawal of the drug. Conclusions: Our findings suggest that short-term use of dexamethasone can temporarily suppress radiation-induced pro-inflammatory cytokine gene expression, but there may be a rebound after drug withdrawal and the drug does little to change the essence and course of the pneumonitic process

Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations.

Science.gov (United States)

Verger, Emmanuelle; Cassinat, Bruno; Chauveau, Aurélie; Dosquet, Christine; Giraudier, Stephane; Schlageter, Marie-Hélène; Ianotto, Jean-Christophe; Yassin, Mohammed A; Al-Dewik, Nader; Carillo, Serge; Legouffe, Eric; Ugo, Valerie; Chomienne, Christine; Kiladjian, Jean-Jacques

2015-12-10

Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy. © 2015 by The American Society of Hematology.

Digital quantification of gene expression in sequential breast cancer biopsies reveals activation of an immune response.

Directory of Open Access Journals (Sweden)

Rinath M Jeselsohn

Full Text Available Advancements in molecular biology have unveiled multiple breast cancer promoting pathways and potential therapeutic targets. Large randomized clinical trials remain the ultimate means of validating therapeutic efficacy, but they require large cohorts of patients and are lengthy and costly. A useful approach is to conduct a window of opportunity study in which patients are exposed to a drug pre-surgically during the interval between the core needle biopsy and the definitive surgery. These are non-therapeutic studies and the end point is not clinical or pathological response but rather evaluation of molecular changes in the tumor specimens that can predict response. However, since the end points of the non-therapeutic studies are biologic, it is critical to first define the biologic changes that occur in the absence of treatment. In this study, we compared the molecular profiles of breast cancer tumors at the time of the diagnostic biopsy versus the definitive surgery in the absence of any intervention using the Nanostring nCounter platform. We found that while the majority of the transcripts did not vary between the two biopsies, there was evidence of activation of immune related genes in response to the first biopsy and further investigations of the immune changes after a biopsy in early breast cancer seem warranted.

Molecular responses to moderate endurance exercise in skeletal muscle

Science.gov (United States)

This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg'¹ x min'¹) immediately (0 hr) and...

Antioxidant responses and cellular adjustments to oxidative stress.

Science.gov (United States)

Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

2015-12-01

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

SOYBEAN - MOLECULAR ASPECTS OF BREEDING

Directory of Open Access Journals (Sweden)

Aleksandra Sudarić

2012-12-01

Full Text Available The book Soybean: Molecular Aspects of Breeding focuses recent progress in our understanding of the genetics and molecular biology of soybean. This book is divided into four parts and contains 22 chapters. Part I, Molecular Biology and Biotechnology focuses advances in molecular biology and laboratory procedures that have been developed recently to manipulate DNA. Part II, Breeding for abiotic stress covers proteomics approaches form as a powerful tool for investigating the molecular mechanisms of the plant responses to various types of abiotic stresses. Part III, Breeding for biotic stress addresses issues related to application of molecular based strategies in order to increase soybean resistance to various biotic factors. Part IV, Recent Technology reviews recent technologies into the realm of soybean monitoring, processing and product use. While the information accumulated in this book is of primary interest for plant breeders, valuable insights are also offered to agronomists, molecular biologists, physiologists, plant pathologists, food scientists and students. The book is a result of efforts made by many experts from different countries (USA, Japan, Croatia, Serbia, China, Canada, Malawi, Iran, Hong Kong, Brasil, Mexico.

The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways.

Science.gov (United States)

Vajjhala, Parimala R; Ve, Thomas; Bentham, Adam; Stacey, Katryn J; Kobe, Bostjan

2017-06-01

The innate immune system is the first line of defense against infection and responses are initiated by pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs). PRRs also detect endogenous danger-associated molecular patterns (DAMPs) that are released by damaged or dying cells. The major PRRs include the Toll-like receptor (TLR) family members, the nucleotide binding and oligomerization domain, leucine-rich repeat containing (NLR) family, the PYHIN (ALR) family, the RIG-1-like receptors (RLRs), C-type lectin receptors (CLRs) and the oligoadenylate synthase (OAS)-like receptors and the related protein cyclic GMP-AMP synthase (cGAS). The different PRRs activate specific signaling pathways to collectively elicit responses including the induction of cytokine expression, processing of pro-inflammatory cytokines and cell-death responses. These responses control a pathogenic infection, initiate tissue repair and stimulate the adaptive immune system. A central theme of many innate immune signaling pathways is the clustering of activated PRRs followed by sequential recruitment and oligomerization of adaptors and downstream effector enzymes, to form higher-order arrangements that amplify the response and provide a scaffold for proximity-induced activation of the effector enzymes. Underlying the formation of these complexes are co-operative assembly mechanisms, whereby association of preceding components increases the affinity for downstream components. This ensures a rapid immune response to a low-level stimulus. Structural and biochemical studies have given key insights into the assembly of these complexes. Here we review the current understanding of assembly of immune signaling complexes, including inflammasomes initiated by NLR and PYHIN receptors, the myddosomes initiated by TLRs, and the MAVS CARD filament initiated by RIG-1. We highlight the co-operative assembly mechanisms during assembly of each of these complexes. Copyright �

Predicting placebo response in adolescents with major depressive disorder: The Adolescent Placebo Impact Composite Score (APICS).

Science.gov (United States)

Nakonezny, Paul A; Mayes, Taryn L; Byerly, Matthew J; Emslie, Graham J

2015-09-01

The aim of this study was to construct a composite scoring system to predict the probability of placebo response in adolescents with Major Depressive Disorder (MDD). Participants of the current study were 151 adolescents (aged 12-17 years) who were randomized to the placebo arm (placebo transdermal patches) of a randomized controlled trial (RCT) comparing the selegiline transdermal patch with placebo (DelBello et al., 2014). The primary outcome of response was defined as a CGI-I score of 1 or 2 (very much or much improved) at week 12 (study-end) or exit. As a first step, a multiple logistic mixed model was used to estimate the odds of placebo response from each predictor in the model, including age, CDRS-R total at baseline (depressive symptom severity), history of recurrent depression (yes vs. no), sex (female vs. male), and race (non-Caucasian vs. Caucasian). On the basis of the initial logistic mixed model analysis, we then constructed an Adolescent Placebo Impact Composite Score (APICS) that became the sole predictor in a re-specified Bayesian logistic regression model to estimate the probability of placebo response. Finally, the AUC for the APICS was tested against a nominal area of 0.50 to evaluate how well the APICS discriminated placebo response status. Among the 151 adolescents, with a mean age of 14.6 years (SD = 1.6) and a mean baseline CDRS-R total of 60.6 (SD = 12.1), 68.2% were females, 50.3% was Caucasian, and 39.7% had a history of recurrent depression. Placebo response rate was 58.3%. Based on the logistic mixed model, the re-specified equation with the highest discriminatory ability to estimate the probability of placebo response was APICS = age + (0.32 × CDRS-R Total at baseline) + (-2.85 × if female) + (-5.50 × if history of recurrent depression) + (-5.85 × if non-Caucasian). The AUC for this model was 0.59 (p = .049). Within a Bayesian decision-theoretic framework, in 95.5% of the time, the 10,000 posterior Monte Carlo samples suggested

Medicinal plant phytochemicals and their inhibitory activities against pancreatic lipase: molecular docking combined with molecular dynamics simulation approach

OpenAIRE

Ahmed, Bilal; Ali Ashfaq, Usman; Mirza, Muhammad Usman

2017-01-01

Obesity is the worst health risk worldwide, which is linked to a number of diseases. Pancreatic lipase is considered as an affective cause of obesity and can be a major target for controlling the obesity. The present study was designed to find out best phytochemicals against pancreatic lipase through molecular docking combined with molecular dynamics (MD) simulation. For this purpose, a total of 3770 phytochemicals were docked against pancreatic lipase and ranked them on the basis of binding ...

Fast response dry-type artificial molecular muscles with [c2]daisy chains

Science.gov (United States)

Iwaso, Kazuhisa; Takashima, Yoshinori; Harada, Akira

2016-06-01

Hierarchically organized myosin and actin filaments found in biological systems exhibit contraction and expansion behaviours that produce work and force by consuming chemical energy. Inspired by these naturally occurring examples, we have developed photoresponsive wet- and dry-type molecular actuators built from rotaxane-based compounds known as [c2]daisy chains (specifically, [c2]AzoCD2 hydrogel and [c2]AzoCD2 xerogel). These actuators were prepared via polycondensation between four-armed poly(ethylene glycol) and a [c2]daisy chain based on α-cyclodextrin as the host component and azobenzene as a photoresponsive guest component. The light-induced actuation arises from the sliding motion of the [c2]daisy chain unit. Ultraviolet irradiation caused the gels to bend towards the light source. The response of the [c2]AzoCD2 xerogel, even under dry conditions, is very fast (7° every second), which is 10,800 times faster than the [c2]AzoCD2 hydrogel (7° every 3 h). In addition, the [c2]AzoCD2 xerogel was used as a crane arm to lift an object using ultraviolet irradiation to produce mechanical work.

Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital

Directory of Open Access Journals (Sweden)

Samuel Roosevelt Campos dos Reis

2013-06-01

Full Text Available Objetive: The aim of this study was to identify the reasons for failure in adherence to imatinib mesylate treatment in chronic myeloid leukemia. Methods: A retrospective review was performed of 100 non-electronic records of patients with Ph+ chronic myeloid leukemia treated with imatinib mesylate. The study period was from January 2001 to January2011. Data were analyzed by Chi-Square and Correspondence analysis using the Statistical Analysis System software package. Results: At the beginning of treatment 41% of patients were in advanced stages of the disease. The unavailability of the drug (44.8% and myelotoxicity (25.7% were the most frequent reasons for interruption. The adherence rate was 95% induced complete cytogenetic response, major cytogenetic response and major molecular response. Conclusion: The population of this study obtained lower-than-expected therapeutic responses compared to other studies.

[Molecular updates on Usher syndrome].

Science.gov (United States)

Roux, A-F

2005-01-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by the association of sensorineural hearing loss and retinitis pigmentosa (RP). Usher syndrome is both clinically and genetically heterogeneous. Three clinical subtypes are defined with respect to vestibular dysfunction and the degree of hearing loss. Type I (USH1) patients have profound hearing loss and vestibular dysfunction from birth. Type II (USH2) is the most frequent and patients tend to have less severe hearing impairment and normal vestibular response. Type III (USH3) is characterized by a progressive loss of hearing and is found more frequently among Finnish patients. Recently, major breakthroughs have been made in the molecular genetics of Usher syndrome as a number of chromosomal loci and causative genes have been identified in each clinical subtype. Twelve loci are known and the corresponding genes have been cloned for six of them. Although their functions are not always clearly established, a common role is emerging for the proteins identified within each subtype. As a result, each subtype could emanate from defects affecting distinct cellular mechanisms.

Tea consumption and the risk of five major cancers: a dose–response meta-analysis of prospective studies

Science.gov (United States)

2014-01-01

Background We conducted a dose–response meta-analysis of prospective studies to summarize evidence of the association between tea consumption and the risk of breast, colorectal, liver, prostate, and stomach cancer. Methods We searched PubMed and two other databases. Prospective studies that reported risk ratios (RRs) with 95% confidence intervals (CIs) of cancer risk for ≥3 categories of tea consumption were included. We estimated an overall RR with 95% CI for an increase of three cups/day of tea consumption, and, usingrestricted cubic splines, we examined a nonlinear association between tea consumption and cancer risk. Results Forty-one prospective studies, with a total of 3,027,702 participants and 49,103 cancer cases, were included. From the pooled overall RRs, no inverse association between tea consumption and risk of five major cancers was observed. However, subgroup analysis showed that increase in consumption of three cups of black tea per day was a significant risk factor for breast cancer (RR, 1.18; 95% CI, 1.05-1.32). Conclusion Ourresults did not show a protective role of tea in five major cancers. Additional large prospective cohort studies are needed to make a convincing case for associations. PMID:24636229

DNA Modification Study of Major Depressive Disorder: Beyond Locus-by-Locus Comparisons

NARCIS (Netherlands)

Oh, G.; Wang, S.C.; Pal, M.; Chen, Z.F.; Khare, T.; Tochigi, M.; Ng, C.; Yang, Y.A.; Kwan, A.; Kaminsky, Z.A.; Mill, Jonathan; Gunasinghe, C.; Tackett, J.L.; Gottesman, I.I.; Willemsen, G.; de Geus, E.J.C.; Vink, J.M.; Slagboom, P.E.; Wray, N.R.; Heath, A.C.; Montgomery, G.W.; Turecki, G.; Martin, N.G.; Boomsma, D.I.; McGuffin, P.; Kustra, R.; Petronis, A.

2015-01-01

Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

DNA modification study of major depressive disorder: Beyond locus-by-locus comparisons

NARCIS (Netherlands)

Oh, G.; Wang, S.C.; Pal, M.; Chen, Z.F.; Khare, T.; Tochigi, M.; Ng, C.; Yang, Y.A.; Kwan, A.; Kaminsky, Z.A.; Mill, J.; Gunasinghe, C.; Tackett, J.L.; Gottesman, I.I.; Willemsen, G.; Geus, E.J.C. de; Vink, J.M.; Slagboom, P.E.; Wray, N.R.; Heath, A.C.; Montgomery, G.W.; Turecki, G.; Martin, N.G.; Boomsma, D.I.; McGuffin, P.; Kustra, R.; Petronis, A.

2015-01-01

Background: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined.

Global patterns of insect diversification: towards a reconciliation of fossil and molecular evidence?

Science.gov (United States)

Condamine, Fabien L; Clapham, Matthew E; Kergoat, Gael J

2016-01-18

Macroevolutionary studies of insects at diverse taxonomic scales often reveal dynamic evolutionary patterns, with multiple inferred diversification rate shifts. Responses to major past environmental changes, such as the Cretaceous Terrestrial Revolution, or the development of major key innovations, such as wings or complete metamorphosis are usually invoked as potential evolutionary triggers. However this view is partially contradicted by studies on the family-level fossil record showing that insect diversification was relatively constant through time. In an attempt to reconcile both views, we investigate large-scale insect diversification dynamics at family level using two distinct types of diversification analyses on a molecular timetree representing ca. 82% of the extant families, and reassess the insect fossil diversity using up-to-date records. Analyses focusing on the fossil record recovered an early burst of diversification, declining to low and steady rates through time, interrupted by extinction events. Phylogenetic analyses showed that major shifts of diversification rates only occurred in the four richest holometabolous orders. Both suggest that neither the development of flight or complete metamorphosis nor the Cretaceous Terrestrial Revolution environmental changes induced immediate changes in diversification regimes; instead clade-specific innovations likely promoted the diversification of major insect orders.

Molecular alterations and biomarkers in colorectal cancer

Science.gov (United States)

Grady, William M.; Pritchard, Colin C.

2013-01-01

The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

Molecular Diagnosis of Tuberculosis.

Science.gov (United States)

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

Science.gov (United States)

Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Miller, John P.; Gopalakrishnan, Vancheswaran; Wang, Feng; Cooper, Zachary A.; Reddy, Sangeetha M.; Gumbs, Curtis; Little, Latasha; Chang, Qing; Chen, Wei-Shen; Wani, Khalida; Petaccia De Macedo, Mariana; Chen, Eveline; Austin-Breneman, Jacob L.; Jiang, Hong; Roszik, Jason; Tetzlaff, Michael T.; Davies, Michael A.; Gershenwald, Jeffrey E.; Tawbi, Hussein; Lazar, Alexander J.; Hwu, Patrick; Hwu, Wen-Jen; Diab, Adi; Glitza, Isabella C.; Patel, Sapna P.; Woodman, Scott E.; Amaria, Rodabe N.; Prieto, Victor G.; Hu, Jianhua; Sharma, Padmanee; Allison, James P.; Chin, Lynda; Zhang, Jianhua; Wargo, Jennifer A.; Futreal, P. Andrew

2018-01-01

Immune checkpoint blockade produces clinical benefit in many patients. However better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1), and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T-cell receptor sequencing (TCR-seq) and whole exome sequencing (WES) within the same cohort, and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of copy number alterations identified a higher burden of copy number loss in non-responders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was non-redundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. PMID:28251903

The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

Directory of Open Access Journals (Sweden)

Michael Nevels

2009-11-01

Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

Science.gov (United States)

Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

2014-01-01

Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

Prospects of molecular markers in Fusarium species diversity

DEFF Research Database (Denmark)

Nayaka, S. Chandra; Wulff, Ednar Gadelha; Udayashankar, A.C.

2011-01-01

focuses of various molecular-based techniques employed to study the diversity of Fusarium species causing diseases in major food crops. An introduction of fusarial diseases and their mycotoxins and molecular-marker-based methods for detection introduce the concept of marker application. Various well...... for generation of probes and their use in phylogeny of Fusarium spp. are also presented. The concluding part emphasizes the value of molecular markers for assessing genetic variability and reveals that molecular tools are indispensable for providing information not only of one Fusarium species but on whole......-known molecular techniques such as random amplified polymorphic DNA, amplification fragment length polymorphism, etc. to more modern ones such as DNA microarrays, DNA barcoding, and pyrosequencing and their application form the core of the review. Target regions in the genome which can be potential candidates...

Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry

OpenAIRE

Luis R. Domingo

2016-01-01

A new theory for the study of the reactivity in Organic Chemistry, named Molecular Electron Density Theory (MEDT), is proposed herein. MEDT is based on the idea that while the electron density distribution at the ground state is responsible for physical and chemical molecular properties, as proposed by the Density Functional Theory (DFT), the capability for changes in electron density is responsible for molecular reactivity. Within MEDT, the reactivity in Organic Chemistry is studied through ...

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants.

Science.gov (United States)

Khan, Shahneaz Ali; Desclozeaux, Marion; Waugh, Courtney; Hanger, Jon; Loader, Jo; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus). In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP) antigen-based vaccine, combined with immune stimulating complex (ISC) adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A) responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP with Two Different Adjuvants.

Directory of Open Access Journals (Sweden)

Shahneaz Ali Khan

Full Text Available Developing a vaccine against Chlamydia is key to combating widespread mortalities and morbidities associated with this infection in koalas (Phascolarctos cinereus. In previous studies, we have shown that two or three doses of a Recombinant Major Outer Membrane Protein (rMOMP antigen-based vaccine, combined with immune stimulating complex (ISC adjuvant, results in strong cellular and humoral immune responses in koalas. We have also separately evaluated a single dose vaccine, utilising a tri-adjuvant formula that comprises polyphosphazine based poly I: C and host defense peptides, with the same antigen. This formulation also produced strong cellular and humoral immune responses in captive koalas. In this current study, we directly compared the host immune responses of two sub-groups of wild Chlamydia negative koalas in one population vaccinated with the rMOMP protein antigen and adjuvanted with either the ISC or tri-adjuvant formula. Overall, both adjuvants produced strong Chlamydia-specific cellular (IFN-γ and IL-17A responses in circulating PBMCs as well as MOMP-specific and functional, in vitro neutralising antibodies. While the immune responses were similar, there were adjuvant-specific immune differences between the two adjuvants, particularly in relation to the specificity of the MOMP epitope antibody responses.

Individual response to ionising radiation: What predictive assay(s) to choose?

International Nuclear Information System (INIS)

Granzotto, A.; Viau, M.; Devic, C.; Maalouf, M.; Thomas, Ch.; Vogin, G.; Foray, N.; Granzotto, A.; Vogin, G.; Balosso, J.; Joubert, A.; Maalouf, M.; Vogin, G.; Colin, C.; Malek, K.; Balosso, J.; Colin, C.

2011-01-01

Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) [1]. To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomics technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensing and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavored to analyse the contributions of these major approaches to predict human radiosensitivity. (authors)

Subtype and pathway specific responses to anticancer compounds in breast cancer.

Science.gov (United States)

Heiser, Laura M; Sadanandam, Anguraj; Kuo, Wen-Lin; Benz, Stephen C; Goldstein, Theodore C; Ng, Sam; Gibb, William J; Wang, Nicholas J; Ziyad, Safiyyah; Tong, Frances; Bayani, Nora; Hu, Zhi; Billig, Jessica I; Dueregger, Andrea; Lewis, Sophia; Jakkula, Lakshmi; Korkola, James E; Durinck, Steffen; Pepin, François; Guan, Yinghui; Purdom, Elizabeth; Neuvial, Pierre; Bengtsson, Henrik; Wood, Kenneth W; Smith, Peter G; Vassilev, Lyubomir T; Hennessy, Bryan T; Greshock, Joel; Bachman, Kurtis E; Hardwicke, Mary Ann; Park, John W; Marton, Laurence J; Wolf, Denise M; Collisson, Eric A; Neve, Richard M; Mills, Gordon B; Speed, Terence P; Feiler, Heidi S; Wooster, Richard F; Haussler, David; Stuart, Joshua M; Gray, Joe W; Spellman, Paul T

2012-02-21

Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

Molecular profiling of interspecific lowland rice populations derived ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... Molecular profiling of interspecific lowland rice populations ... Both cluster and principal component analyses revealed two major groups ...... simulations. Theor ... inheritance, chromosomal location, and population dynamics.

Adaptation to environmental temperature is a major determinant of molecular evolutionary rates in archaea.

Science.gov (United States)

Groussin, Mathieu; Gouy, Manolo

2011-09-01

Methods to infer the ancestral conditions of life are commonly based on geological and paleontological analyses. Recently, several studies used genome sequences to gain information about past ecological conditions taking advantage of the property that the G+C and amino acid contents of bacterial and archaeal ribosomal DNA genes and proteins, respectively, are strongly influenced by the environmental temperature. The adaptation to optimal growth temperature (OGT) since the Last Universal Common Ancestor (LUCA) over the universal tree of life was examined, and it was concluded that LUCA was likely to have been a mesophilic organism and that a parallel adaptation to high temperature occurred independently along the two lineages leading to the ancestors of Bacteria on one side and of Archaea and Eukarya on the other side. Here, we focus on Archaea to gain a precise view of the adaptation to OGT over time in this domain. It has been often proposed on the basis of indirect evidence that the last archaeal common ancestor was a hyperthermophilic organism. Moreover, many results showed the influence of environmental temperature on the evolutionary dynamics of archaeal genomes: Thermophilic organisms generally display lower evolutionary rates than mesophiles. However, to our knowledge, no study tried to explain the differences of evolutionary rates for the entire archaeal domain and to investigate the evolution of substitution rates over time. A comprehensive archaeal phylogeny and a non homogeneous model of the molecular evolutionary process allowed us to estimate ancestral base and amino acid compositions and OGTs at each internal node of the archaeal phylogenetic tree. The last archaeal common ancestor is predicted to have been hyperthermophilic and adaptations to cooler environments can be observed for extant mesophilic species. Furthermore, mesophilic species present both long branches and high variation of nucleotide and amino acid compositions since the last archaeal

Interpopulational variability of molecular responses to ionizing radiation in freshwater bivalves Anodonta anatina (Unionidae)

Energy Technology Data Exchange (ETDEWEB)

Falfushynska, H. [Research Laboratory of Comparative Biochemistry and Molecular Biology, Ternopil National Pedagogical University, 2, Kryvonosa Str, Ternopil 46027 (Ukraine); Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States); Department of General Chemistry, I.Ya. Horbachevsky Ternopil State Medical University, 1, Maidan Voli, Ternopil 46001 (Ukraine); Gnatyshyna, L. [Research Laboratory of Comparative Biochemistry and Molecular Biology, Ternopil National Pedagogical University, 2, Kryvonosa Str, Ternopil 46027 (Ukraine); Department of General Chemistry, I.Ya. Horbachevsky Ternopil State Medical University, 1, Maidan Voli, Ternopil 46001 (Ukraine); Yurchak, I.; Stoliar, O. [Research Laboratory of Comparative Biochemistry and Molecular Biology, Ternopil National Pedagogical University, 2, Kryvonosa Str, Ternopil 46027 (Ukraine); Sokolova, I.M., E-mail: isokolova@uncc.edu [Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC 28223 (United States)

2016-10-15

Freshwater ecosystems are exposed to multiple anthropogenic stressors including chemical pollution and warming that can affect health of the resident organisms and their responses to novel challenges. We investigated the of in situ exposure history on molecular responses to a novel stressor, ionizing radiation, in unionid mollusks Anodonta anatina. Males from pristine (F-), agricultural (A-) sites and a cooling reservoir of a nuclear power plant (N-site) were exposed to acute low dose (2 mGy) X-ray radiation followed by 14 days of recovery (R-groups) or to control conditions (C-groups). Biomarkers of oxidative stress, geno-, cyto- and neurotoxicity were used to assess cellular injury and stress. Control group from the cooling reservoir (CN) had higher background levels of caspase-3 activity, metallothionein concentrations and nuclear lesions and lower levels of superoxide dismutase (SOD) and glutathione in the gills compared to other control groups (CF and CA). Irradiation induced cellular damage in mussels from all three sites including increased levels of nuclear lesions in hemocytes, depletion of caspase-3, suppression of superoxide dismutase and catalase activities, an increase of the lipid peroxidation and oxidized glutathione levels, as well as down-regulation of cholinesterase indicating neurotoxicity. The up-regulation of ethoxyresorufin-O-deethylase activity in the digestive gland and vitellogenin-like protein level in gonads were also found in radiation-exposed groups indicating feminization of males and disturbances of xenobiotic metabolism. The RA-group showed the greatest magnitude of radiation-induced stress responses compared to the other two groups. Overall, unionid mollusks, particularly those from a chronically polluted agricultural site, were highly sensitive to low-dose radiation (2 mGy) indicating limitations of stress protection mechanisms to deal with multiple stressors. - Highlights: • Habitat-specific effects of irradiation were studied

Interpopulational variability of molecular responses to ionizing radiation in freshwater bivalves Anodonta anatina (Unionidae)

International Nuclear Information System (INIS)

Falfushynska, H.; Gnatyshyna, L.; Yurchak, I.; Stoliar, O.; Sokolova, I.M.

2016-01-01

Freshwater ecosystems are exposed to multiple anthropogenic stressors including chemical pollution and warming that can affect health of the resident organisms and their responses to novel challenges. We investigated the of in situ exposure history on molecular responses to a novel stressor, ionizing radiation, in unionid mollusks Anodonta anatina. Males from pristine (F-), agricultural (A-) sites and a cooling reservoir of a nuclear power plant (N-site) were exposed to acute low dose (2 mGy) X-ray radiation followed by 14 days of recovery (R-groups) or to control conditions (C-groups). Biomarkers of oxidative stress, geno-, cyto- and neurotoxicity were used to assess cellular injury and stress. Control group from the cooling reservoir (CN) had higher background levels of caspase-3 activity, metallothionein concentrations and nuclear lesions and lower levels of superoxide dismutase (SOD) and glutathione in the gills compared to other control groups (CF and CA). Irradiation induced cellular damage in mussels from all three sites including increased levels of nuclear lesions in hemocytes, depletion of caspase-3, suppression of superoxide dismutase and catalase activities, an increase of the lipid peroxidation and oxidized glutathione levels, as well as down-regulation of cholinesterase indicating neurotoxicity. The up-regulation of ethoxyresorufin-O-deethylase activity in the digestive gland and vitellogenin-like protein level in gonads were also found in radiation-exposed groups indicating feminization of males and disturbances of xenobiotic metabolism. The RA-group showed the greatest magnitude of radiation-induced stress responses compared to the other two groups. Overall, unionid mollusks, particularly those from a chronically polluted agricultural site, were highly sensitive to low-dose radiation (2 mGy) indicating limitations of stress protection mechanisms to deal with multiple stressors. - Highlights: • Habitat-specific effects of irradiation were studied

Molecular evolution and the latitudinal biodiversity gradient.

Science.gov (United States)

Dowle, E J; Morgan-Richards, M; Trewick, S A