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Sample records for major molecular response

  1. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

    2008-01-01

    with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  2. The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

    Directory of Open Access Journals (Sweden)

    Ilana Zalcberg Renault

    2011-12-01

    Full Text Available Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging.

  3. The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

    Science.gov (United States)

    Renault, Ilana Zalcberg; Scholl, Vanesa; Hassan, Rocio; Capelleti, Paola; de Lima, Marcos; Cortes, Jorge

    2011-01-01

    Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging. PMID:23049363

  4. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromos...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  5. Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

    Science.gov (United States)

    Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

    2017-10-01

    With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

  6. A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

    Directory of Open Access Journals (Sweden)

    Vanessa Augis

    Full Text Available BIM is essential for the response to tyrosine-kinase inhibitors (TKI in chronic myeloid leukaemia (CML patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations.BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population as a case-control study. Real-time quantitative PCR (RT qPCR was performed to assess Bim expression in our reference population.No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP c465C>T (rs724710. A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p = 0.0065. T allele frequency was higher in non responsive patients than in the reference population (p = 0.0049. Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (pT SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients.

  7. 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

  8. Molecular connectivity disruptions in males with major depressive disorder.

    Science.gov (United States)

    Pillai, Rajapillai Li; Zhang, Mengru; Yang, Jie; Mann, J John; Oquendo, Maria A; Parsey, Ramin V; DeLorenzo, Christine

    2018-01-01

    In most positron emission tomography (PET) molecular brain imaging studies, regions of interest have been defined anatomically and examined in isolation. However, by defining regions based on physiology and examining relationships between them, we may derive more sensitive measures of receptor abnormalities in conditions such as major depressive disorder (MDD). Using an average of 52 normalized binding potential maps, acquired using radiotracer [ 11 C]-WAY100635 and full arterial input analysis, we identified two molecular volumes of interest (VOIs) with contiguously high serotonin 1A receptor (5-HT 1A ) binding sites: the olfactory sulcus (OLFS) and a band of tissue including piriform, olfactory, and entorhinal cortex (PRF). We applied these VOIs to a separate cohort of 25 healthy control males and 16 males with MDD who received [ 11 C]-WAY100635 imaging. Patients with MDD had significantly higher binding than controls in both VOIs, ( p molecular connectivity, i.e. the correlation between binding of raphe nucleus (RN) 5-HT 1A autoreceptors and post-synaptic receptors in molecular VOIs. Molecular connectivity was significant in healthy controls ( p molecular connectivity allowed identification of MDD cases with high sensitivity (81%) and specificity (88%).

  9. 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.

  10. 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.

  11. Molecular Genotype Identification of Different Chickens: Major Histocompatibility Complex

    Directory of Open Access Journals (Sweden)

    Hongzhi Wang

    2014-09-01

    Full Text Available Chicken is a main poultry in China. Molecular breeding for disease resistance plays an important role in the control of diseases, especially infectious diseases. Choice of genes for disease resistance is the key technology of molecular breeding. The major histocompatibility complex (MHC is of great interest to poultry breeding scientists for its extraordinary polymorphism and close relation with traits of resistance against infectious diseases. The MHC-B haplotype plays an important role in the study of disease resistance in chicken. The traditional chicken MHC-B haplotype is commonly defined by serologic reactions of erythrocytes and the majority of studies have been conducted in Leghorn and broiler but study about other chicken breeds is little. In this study, firstly, the microsatellite marker LEI0258 which is located within the MHC was sequenced by using target sequence capture assay in different chicken breeds, and then according to the number of repeated structures and polymorphic sequences in microsatellite, sequence information for the region defined by LEI0258 was obtained for different haplotypes. Afterwards, we identified the relation between MHC-B haplotypes and disease resistance. Collectively, these observed results provided the reference data for disease-resistant breeding association with blood type and for further study of MHC gene function in poultry.

  12. 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.

  13. Genetics of mechanisms controlling responses to two major pathogens in broiler and layer chickens

    DEFF Research Database (Denmark)

    Hamzic, Edin

    The objective of this thesis was to improve the understanding of molecular mechanisms controlling the response to two major pathogens, Eimeria maxima (coccidiosis) and infectious bronchitis virus (IBV), in broiler and layer chickens, respectively. Breeding for the improved response to the two...

  14. 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.

  15. Academic search in response to major scientific events

    NARCIS (Netherlands)

    Li, X.; de Rijke, M.

    2017-01-01

    In this paper, we look at the search behavior of users of an academic search engine and in particular, their query patterns following the occurrence of major scientific events. We select Nobel Prize announcements as major scientific events and observe how academic searchers behave in response to

  16. 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

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. 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.

  2. A Learner-Centered Molecular Modeling Exercise for Allied Health Majors in a Biochemistry Class

    Science.gov (United States)

    Fletcher, Terace M.; Ershler, Jeff

    2014-01-01

    Learner-centered molecular modeling exercises in college science courses can be especially challenging for nonchemistry majors as students typically have a higher degree of anxiety and may not appreciate the relevance of the work. This article describes a learner-centered project given to allied health majors in a Biochemistry course. The project…

  3. Recent Molecular Advances on Downstream Plant Responses to Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Cláudia Regina Batista de Souza

    2012-07-01

    Full Text Available Abiotic stresses such as extremes of temperature and pH, high salinity and drought, comprise some of the major factors causing extensive losses to crop production worldwide. Understanding how plants respond and adapt at cellular and molecular levels to continuous environmental changes is a pre-requisite for the generation of resistant or tolerant plants to abiotic stresses. In this review we aimed to present the recent advances on mechanisms of downstream plant responses to abiotic stresses and the use of stress-related genes in the development of genetically engineered crops.

  4. Professionally responsible intrapartum management of patients with major mental disorders.

    Science.gov (United States)

    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.

  5. Essential concepts and underlying theories from physics, chemistry, and mathematics for "biochemistry and molecular biology" majors.

    Science.gov (United States)

    Wright, Ann; Provost, Joseph; Roecklein-Canfield, Jennifer A; 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 from around the country. The workshops have focused on developing lists of Core Principles or Foundational Concepts in Biochemistry and Molecular Biology, a list of foundational skills, and foundational concepts from Physics, Chemistry, and Mathematics that all Biochemistry or Molecular Biology majors must understand to complete their major coursework. The allied fields working group created a survey to validate foundational concepts from Physics, Chemistry, and Mathematics identified from participant feedback at various workshops. One-hundred twenty participants responded to the survey and 68% of the respondents answered yes to the question: "We have identified the following as the core concepts and underlying theories from Physics, Chemistry, and Mathematics that Biochemistry majors or Molecular Biology majors need to understand after they complete their major courses: 1) mechanical concepts from Physics, 2) energy and thermodynamic concepts from Physics, 3) critical concepts of structure from chemistry, 4) critical concepts of reactions from Chemistry, and 5) essential Mathematics. In your opinion, is the above list complete?" Respondents also delineated subcategories they felt should be included in these broad categories. From the results of the survey and this analysis the allied fields working group constructed a consensus list of allied fields concepts, which will help inform Biochemistry and Molecular Biology educators when considering the ASBMB recommended curriculum for Biochemistry or Molecular Biology majors and in the development of appropriate assessment tools to gauge student understanding of how these concepts relate to biochemistry and molecular biology. © 2013 by The International Union of Biochemistry and Molecular Biology.

  6. Indigoid Photoswitches: Visible Light Responsive Molecular Tools.

    Science.gov (United States)

    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

  7. 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.

  8. 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

  9. Emergency Response and the International Charter Space and Major Disasters

    Science.gov (United States)

    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

  10. Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii.

    Directory of Open Access Journals (Sweden)

    Carolina Firacative

    Full Text Available Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p 0.05, 21 (five VGI, five VGII, four VGIII and seven VGIV were less virulent (p <0.05 while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001. No differences in growth rate at 37°C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05. The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature, that maybe crucial for the development and progression of cryptococcosis.

  11. 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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Practices and Exploration on Competition of Molecular Biological Detection Technology among Students in Food Quality and Safety Major

    Science.gov (United States)

    Chang, Yaning; Peng, Yuke; Li, Pengfei; Zhuang, Yingping

    2017-01-01

    With the increasing importance in the application of the molecular biological detection technology in the field of food safety, strengthening education in molecular biology experimental techniques is more necessary for the culture of the students in food quality and safety major. However, molecular biology experiments are not always in curricula…

  17. An integrative model of employee responses to major organisational change.

    OpenAIRE

    Kimberley, Nellie Anne

    2017-01-01

    One of the enduring issues facing organisations relates to the high number of change initiatives that fail outright or only partially meet expectations (Beer & Nohria, 2000). Although there are many potential causes of failed change, much of the extant change identifies resistance to change as the major source of this problem. In order to bring about successful organisational change, it is important that managers create a change-ready environment, one where employees accept and affectively co...

  18. Personality, Stressful Life Events, and Treatment Response in Major Depression

    Science.gov (United States)

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. Optimization of emergency response to major nuclear accidents

    International Nuclear Information System (INIS)

    Papazoglou, I.A.; Christou, M.D.

    1991-01-01

    A methodology for the optimization of the short-term emergency response in the event of a nuclear accident has been developed. The method aims at an optimum combination of protective actions in the presence of a multitude of conflicting objectives and under uncertainty. Conflicting objectives arise when the minimization of the potential adverse effects of an accident and the simultaneous minimization of the associated socioeconomic impacts is attempted. Additional conflicting objectives appear whenever an emergency plan tends to decrease a particular health effect (e.g. acute deaths) while at the same time it increases another (e.g. latent deaths). The uncertainty is due to the multitude of the possible accident scenarios and their respective probability of occurrence, the stochastic variability in the weather conditions and in the variability and/or lack of knowledge in the parameters of the risk assessment models. A multiobjective optimization approach is adopted in a dynamic programming scheme. An emergency protective plan consists of defining a protective action (e.g. evacuation, sheltering) at each spatial cell around the plant. Three criteria (evaluators) are used as the objective functions of the problem, namely, acute fatalities, latent effects and socioeconomic cost. The optimization procedure defines the efficient frontier, i.e. all emergency plans that are not dominated by another in all three criteria. No value trade-offs are necessary up to this point

  4. Practices and exploration on competition of molecular biological detection technology among students in food quality and safety major.

    Science.gov (United States)

    Chang, Yaning; Peng, Yuke; Li, Pengfei; Zhuang, Yingping

    2017-07-08

    With the increasing importance in the application of the molecular biological detection technology in the field of food safety, strengthening education in molecular biology experimental techniques is more necessary for the culture of the students in food quality and safety major. However, molecular biology experiments are not always in curricula of Food quality and safety Majors. This paper introduced a project "competition of molecular biological detection technology for food safety among undergraduate sophomore students in food quality and safety major", students participating in this project needed to learn the fundamental molecular biology experimental techniques such as the principles of molecular biology experiments and genome extraction, PCR and agarose gel electrophoresis analysis, and then design the experiments in groups to identify the meat species in pork and beef products using molecular biological methods. The students should complete the experimental report after basic experiments, write essays and make a presentation after the end of the designed experiments. This project aims to provide another way for food quality and safety majors to improve their knowledge of molecular biology, especially experimental technology, and enhances them to understand the scientific research activities as well as give them a chance to learn how to write a professional thesis. In addition, in line with the principle of an open laboratory, the project is also open to students in other majors in East China University of Science and Technology, in order to enhance students in other majors to understand the fields of molecular biology and food safety. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):343-350, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  5. 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.

  6. 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

  7. Achieving deeper molecular response is associated with a better clinical outcome in chronic myeloid leukemia patients on imatinib front-line therapy

    Science.gov (United States)

    Etienne, Gabriel; Dulucq, Stéphanie; Nicolini, Franck-Emmanuel; Morisset, Stéphane; Fort, Marie-Pierre; Schmitt, Anna; Etienne, Madeleine; Hayette, Sandrine; Lippert, Eric; Bureau, Caroline; Tigaud, Isabelle; Adiko, Didier; Marit, Gérald; Reiffers, Josy; Mahon, François-Xavier

    2014-01-01

    Sustained imatinib treatment in chronic myeloid leukemia patients can result in complete molecular response allowing discontinuation without relapse. We set out to evaluate the frequency of complete molecular response in imatinib de novo chronic phase chronic myeloid leukemia patients, to identify base-line and under-treatment predictive factors of complete molecular response in patients achieving complete cytogenetic response, and to assess if complete molecular response is associated with a better outcome. A random selection of patients on front-line imatinib therapy (n=266) were considered for inclusion. Complete molecular response was confirmed and defined as MR 4.5 with undetectable BCR-ABL transcript levels. Median follow up was 4.43 years (range 0.79–10.8 years). Sixty-five patients (24%) achieved complete molecular response within a median time of 32.7 months. Absence of spleen enlargement at diagnosis, achieving complete cytogenetic response before 12 months of therapy, and major molecular response during the year following complete cytogenetic response was predictive of achieving further complete molecular response. Patients who achieved complete molecular response had better event-free and failure-free survivals than those with complete cytogenetic response irrespective of major molecular response status (95.2% vs. 64.7% vs. 27.7%, P=0.00124; 98.4% vs. 82.3% vs. 56%, P=0.0335), respectively. Overall survival was identical in the 3 groups. In addition to complete cytogenetic response and major molecular response, further deeper molecular response is associated with better event-free and failure-free survivals, and complete molecular response confers the best outcome. PMID:24362549

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

    Science.gov (United States)

    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.

  9. 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.

  10. 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 ...

  11. 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 ...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

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

    Science.gov (United States)

    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

  15. 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

  16. 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.

  17. 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

  18. Molecular Responses to the Zika Virus in Mosquitoes

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. 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

  2. Comparative molecular cytogenetics of major repetitive sequence families of three Dendrobium species (Orchidaceae) from Bangladesh

    Science.gov (United States)

    Begum, Rabeya; Alam, Sheikh Shamimul; Menzel, Gerhard; Schmidt, Thomas

    2009-01-01

    Background and Aims Dendrobium species show tremendous morphological diversity and have broad geographical distribution. As repetitive sequence analysis is a useful tool to investigate the evolution of chromosomes and genomes, the aim of the present study was the characterization of repetitive sequences from Dendrobium moschatum for comparative molecular and cytogenetic studies in the related species Dendrobium aphyllum, Dendrobium aggregatum and representatives from other orchid genera. Methods In order to isolate highly repetitive sequences, a c0t-1 DNA plasmid library was established. Repeats were sequenced and used as probes for Southern hybridization. Sequence divergence was analysed using bioinformatic tools. Repetitive sequences were localized along orchid chromosomes by fluorescence in situ hybridization (FISH). Key Results Characterization of the c0t-1 library resulted in the detection of repetitive sequences including the (GA)n dinucleotide DmoO11, numerous Arabidopsis-like telomeric repeats and the highly amplified dispersed repeat DmoF14. The DmoF14 repeat is conserved in six Dendrobium species but diversified in representative species of three other orchid genera. FISH analyses showed the genome-wide distribution of DmoF14 in D. moschatum, D. aphyllum and D. aggregatum. Hybridization with the telomeric repeats demonstrated Arabidopsis-like telomeres at the chromosome ends of Dendrobium species. However, FISH using the telomeric probe revealed two pairs of chromosomes with strong intercalary signals in D. aphyllum. FISH showed the terminal position of 5S and 18S–5·8S–25S rRNA genes and a characteristic number of rDNA sites in the three Dendrobium species. Conclusions The repeated sequences isolated from D. moschatum c0t-1 DNA constitute major DNA families of the D. moschatum, D. aphyllum and D. aggregatum genomes with DmoF14 representing an ancient component of orchid genomes. Large intercalary telomere-like arrays suggest chromosomal

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. An overview of HCV molecular biology, replication and immune responses

    Directory of Open Access Journals (Sweden)

    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.

  8. Essential Concepts and Underlying Theories from Physics, Chemistry, and Mathematics for "Biochemistry and Molecular Biology" Majors

    Science.gov (United States)

    Wright, Ann; Provost, Joseph; Roecklein-Canfield, Jennifer A.; 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 from around the country. The workshops have focused on developing lists of Core Principles or Foundational Concepts in Biochemistry and Molecular Biology, a list of foundational skills, and foundational concepts from Physics, Chemistry,…

  9. 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)…

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

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  12. 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)

  13. 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

  14. 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.

  15. 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

  16. Molecular defense response of oil palm to Ganoderma infection.

    Science.gov (United States)

    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.

  17. Bioinformatic Integration of Molecular Networks and Major Pathways Involved in Mice Cochlear and Vestibular Supporting Cells.

    Science.gov (United States)

    Requena, Teresa; Gallego-Martinez, Alvaro; Lopez-Escamez, Jose A

    2018-01-01

    Background : Cochlear and vestibular epithelial non-hair cells (ENHCs) are the supporting elements of the cellular architecture in the organ of Corti and the vestibular neuroepithelium in the inner ear. Intercellular and cell-extracellular matrix interactions are essential to prevent an abnormal ion redistribution leading to hearing and vestibular loss. The aim of this study is to define the main pathways and molecular networks in the mouse ENHCs. Methods : We retrieved microarray and RNA-seq datasets from mouse epithelial sensory and non-sensory cells from gEAR portal (http://umgear.org/index.html) and obtained gene expression fold-change between ENHCs and non-epithelial cells (NECs) against HCs for each gene. Differentially expressed genes (DEG) with a log2 fold change between 1 and -1 were discarded. The remaining genes were selected to search for interactions using Ingenuity Pathway Analysis and STRING platform. Specific molecular networks for ENHCs in the cochlea and the vestibular organs were generated and significant pathways were identified. Results : Between 1723 and 1559 DEG were found in the mouse cochlear and vestibular tissues, respectively. Six main pathways showed enrichment in the supporting cells in both tissues: (1) "Inhibition of Matrix Metalloproteases"; (2) "Calcium Transport I"; (3) "Calcium Signaling"; (4) "Leukocyte Extravasation Signaling"; (5) "Signaling by Rho Family GTPases"; and (6) "Axonal Guidance Si". In the mouse cochlea, ENHCs showed a significant enrichment in 18 pathways highlighting "axonal guidance signaling (AGS)" ( p = 4.37 × 10 -8 ) and "RhoGDI Signaling" ( p = 3.31 × 10 -8 ). In the vestibular dataset, there were 20 enriched pathways in ENHCs, the most significant being "Leukocyte Extravasation Signaling" ( p = 8.71 × 10 -6 ), "Signaling by Rho Family GTPases" ( p = 1.20 × 10 -5 ) and "Calcium Signaling" ( p = 1.20 × 10 -5 ). Among the top ranked networks, the most biologically significant network contained the

  18. 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.

  19. 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

  20. Molecular characterization of 5S ribosomal RNA genes and transcripts in the protozoan parasite Leishmania major.

    Science.gov (United States)

    Moreno-Campos, Rodrigo; Florencio-Martínez, Luis E; Nepomuceno-Mejía, Tomás; Rojas-Sánchez, Saúl; Vélez-Ramírez, Daniel E; Padilla-Mejía, Norma E; Figueroa-Angulo, Elisa; Manning-Cela, Rebeca; Martínez-Calvillo, Santiago

    2016-12-01

    Eukaryotic 5S rRNA, synthesized by RNA polymerase III (Pol III), is an essential component of the large ribosomal subunit. Most organisms contain hundreds of 5S rRNA genes organized into tandem arrays. However, the genome of the protozoan parasite Leishmania major contains only 11 copies of the 5S rRNA gene, which are interspersed and associated with other Pol III-transcribed genes. Here we report that, in general, the number and order of the 5S rRNA genes is conserved between different species of Leishmania. While in most organisms 5S rRNA genes are normally associated with the nucleolus, combined fluorescent in situ hybridization and indirect immunofluorescence experiments showed that 5S rRNA genes are mainly located at the nuclear periphery in L. major. Similarly, the tandemly repeated 5S rRNA genes in Trypanosoma cruzi are dispersed throughout the nucleus. In contrast, 5S rRNA transcripts in L. major were localized within the nucleolus, and scattered throughout the cytoplasm, where mature ribosomes are located. Unlike other rRNA species, stable antisense RNA complementary to 5S rRNA is not detected in L. major.

  1. Mitochondrial molecular clocks and the origin of the major Otocephalan clades (Pisces: Teleostei)

    DEFF Research Database (Denmark)

    Peng, Zuogang; He, Shunping; Wang, Jun

    2006-01-01

    The Otocephala, a clade including ostariophysan and clupeomorph teleosts, represents about a quarter of total fish species diversity, with about 1000 genera and more than 7000 species. A series of recent papers have defended that the origin of this clade and of its major groups may be significantly...... otophysans could have originated before the splitting of the Pangean supercontinent is of extreme importance, since otophysan fishes are among the most useful animal groups for the determination of historical continental relationships. In the present work we examined divergence times for each major...... otocephalan group by an analysis of complete mtDNA sequences, in order to investigate if these divergence times support the hypotheses advanced in recent studies. The complete mtDNA sequences of nine representative non-otocephalan fish species and of twenty-one representative otocephalan species was compared...

  2. Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

    Science.gov (United States)

    Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

    2017-04-01

    All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

  3. Glucose-responsive insulin by molecular and physical design

    Science.gov (United States)

    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.

  4. 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.

  5. 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.

  6. 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.

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

    Science.gov (United States)

    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.

  8. Many-body theory of electrical, thermal and optical response of molecular heterojunctions

    Science.gov (United States)

    Bergfield, Justin Phillip

    In this work, we develop a many-body theory of electronic transport through single molecule junctions based on nonequilibrium Green's functions (NEGFs). The central quantity of this theory is the Coulomb self-energy matrix of the junction SigmaC. SigmaC is evaluated exactly in the sequential-tunneling limit, and the correction due to finite lead-molecule tunneling is evaluated using a conserving approximation based on diagrammatic perturbation theory on the Keldysh contour. In this way, tunneling processes are included to infinite order, meaning that any approximation utilized is a truncation in the physical processes considered rather than in the order of those processes. Our theory reproduces the key features of both the Coulomb blockade and coherent transport regimes simultaneously in a single unified theory. Nonperturbative effects of intramolecular correlations are included, which are necessary to accurately describe the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, essential for a quantitative theory of transport. This work covers four major topics related to transport in single-molecule junctions. First, we use our many-body theory to calculate the nonlinear electrical response of the archetypal Au-1,4-benzenedithiol-Au junction and find irregularly shaped 'molecular diamonds' which have been experimentally observed in some larger molecules but which are inaccessible to existing theoretical approaches. Next, we extend our theory to include heat transport and develop an exact expression for the heat current in an interacting nanostructure. Using this result, we discover that quantum coherence can strongly enhance the thermoelectric response of a device, a result with a number of technological applications. We then develop the formalism to include multi-orbital lead-molecule contacts and multi-channel leads, both of which strongly affect the observable transport. Lastly, we include a dynamic screening correction to

  9. Escitalopram—translating molecular properties into clinical benefit: reviewing the evidence in major depression

    Science.gov (United States)

    Leonard, Brian; Taylor, David

    2010-01-01

    The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents. PMID:20147575

  10. Escitalopram--translating molecular properties into clinical benefit: reviewing the evidence in major depression.

    LENUS (Irish Health Repository)

    Leonard, Brian

    2010-08-01

    The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents.

  11. 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.

  12. 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

  13. Natural selection and molecular evolution in primate PAX9 gene, a major determinant of tooth development.

    Science.gov (United States)

    Pereira, Tiago V; Salzano, Francisco M; Mostowska, Adrianna; Trzeciak, Wieslaw H; Ruiz-Linares, Andrés; Chies, José A B; Saavedra, Carmen; Nagamachi, Cleusa; Hurtado, Ana M; Hill, Kim; Castro-de-Guerra, Dinorah; Silva-Júnior, Wilson A; Bortolini, Maria-Cátira

    2006-04-11

    Large differences in relation to dental size, number, and morphology among and within modern human populations and between modern humans and other primate species have been observed. Molecular studies have demonstrated that tooth development is under strict genetic control, but, the genetic basis of primate tooth variation remains unknown. The PAX9 gene, which codes for a paired domain-containing transcription factor that plays an essential role in the development of mammal dentition, has been associated with selective tooth agenesis in humans and mice, which mainly involves the posterior teeth. To determine whether this gene is polymorphic in humans, we sequenced approximately 2.1 kb of the entire four-exon region (exons 1, 2, 3 and 4; 1,026 bp) and exon-intron (1.1 kb) boundaries of 86 individuals sampled from Asian, European, and Native American populations. We provided evidence that human PAX9 polymorphisms are limited to exon 3 only and furnished details about the distribution of a mutation there in 350 Polish subjects. To investigate the pattern of selective pressure on exon 3, we sequenced ortholog regions of this exon in four species of New World monkeys and one gorilla. In addition, orthologous sequences of PAX9 available in public databases were also analyzed. Although several differences were identified between humans and other species, our findings support the view that strong purifying selection is acting on PAX9. New World and Old World primate lineages may, however, have different degrees of restriction for changes in this DNA region.

  14. Molecular analysis and genomic organization of major DNA satellites in banana (Musa spp.).

    Science.gov (United States)

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

    2013-01-01

    Satellite DNA sequences consist of tandemly arranged repetitive units up to thousands nucleotides long in head-to-tail orientation. The evolutionary processes by which satellites arise and evolve include unequal crossing over, gene conversion, transposition and extra chromosomal circular DNA formation. Large blocks of satellite DNA are often observed in heterochromatic regions of chromosomes and are a typical component of centromeric and telomeric regions. Satellite-rich loci may show specific banding patterns and facilitate chromosome identification and analysis of structural chromosome changes. Unlike many other genomes, nuclear genomes of banana (Musa spp.) are poor in satellite DNA and the information on this class of DNA remains limited. The banana cultivars are seed sterile clones originating mostly from natural intra-specific crosses within M. acuminata (A genome) and inter-specific crosses between M. acuminata and M. balbisiana (B genome). Previous studies revealed the closely related nature of the A and B genomes, including similarities in repetitive DNA. In this study we focused on two main banana DNA satellites, which were previously identified in silico. Their genomic organization and molecular diversity was analyzed in a set of nineteen Musa accessions, including representatives of A, B and S (M. schizocarpa) genomes and their inter-specific hybrids. The two DNA satellites showed a high level of sequence conservation within, and a high homology between Musa species. FISH with probes for the satellite DNA sequences, rRNA genes and a single-copy BAC clone 2G17 resulted in characteristic chromosome banding patterns in M. acuminata and M. balbisiana which may aid in determining genomic constitution in interspecific hybrids. In addition to improving the knowledge on Musa satellite DNA, our study increases the number of cytogenetic markers and the number of individual chromosomes, which can be identified in Musa.

  15. 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.

  16. 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.

  17. 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

  18. 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)

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

    Science.gov (United States)

    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

  20. 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

  1. 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

  2. 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...

  3. 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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)

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

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

    Science.gov (United States)

    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).

  2. 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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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.

  7. 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

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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)

  11. 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.

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

    Science.gov (United States)

    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.

  13. 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.

  14. 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...

  15. MALDI-TOF MS enables the rapid identification of the major molecular types within the Cryptococcus neoformans/C. gattii species complex.

    Directory of Open Access Journals (Sweden)

    Carolina Firacative

    Full Text Available BACKGROUND: The Cryptococcus neoformans/C. gattii species complex comprises two sibling species that are divided into eight major molecular types, C. neoformans VNI to VNIV and C. gattii VGI to VGIV. These genotypes differ in host range, epidemiology, virulence, antifungal susceptibility and geographic distribution. The currently used phenotypic and molecular identification methods for the species/molecular types are time consuming and expensive. As Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS offers an effective alternative for the rapid identification of microorganisms, the objective of this study was to examine its potential for the identification of C. neoformans and C. gattii strains at the intra- and inter-species level. METHODOLOGY: Protein extracts obtained via the formic acid extraction method of 164 C. neoformans/C. gattii isolates, including four inter-species hybrids, were studied. RESULTS: The obtained mass spectra correctly identified 100% of all studied isolates, grouped each isolate according to the currently recognized species, C. neoformans and C. gattii, and detected potential hybrids. In addition, all isolates were clearly separated according to their major molecular type, generating greater spectral differences among the C. neoformans molecular types than the C. gattii molecular types, most likely reflecting a closer phylogenetic relationship between the latter. The number of colonies used and the incubation length did not affect the results. No spectra were obtained from intact yeast cells. An extended validated spectral library containing spectra of all eight major molecular types was established. CONCLUSIONS: MALDI-TOF MS is a rapid identification tool for the correct recognition of the two currently recognized human pathogenic Cryptococcus species and offers a simple method for the separation of the eight major molecular types and the detection of hybrid strains within this

  16. 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

  17. "Loser" or "Popular"?: Neural response to social status words in adolescents with major depressive disorder.

    Science.gov (United States)

    Silk, Jennifer S; Lee, Kyung Hwa; Kerestes, Rebecca; Griffith, Julianne M; Dahl, Ronald E; Ladouceur, Cecile D

    2017-12-01

    Concerns about social status are ubiquitous during adolescence, with information about social status often conveyed in text formats. Depressed adolescents may show alterations in the functioning of neural systems supporting processing of social status information. We examined whether depressed youth exhibited altered neural activation to social status words in temporal and prefrontal cortical regions thought to be involved in social cognitive processing, and whether this response was associated with development. Forty-nine adolescents (ages 10-18; 35 female), including 20 with major depressive disorder and 29 controls, were scanned while identifying the valence of words that connoted positive and negative social status. Results indicated that depressed youth showed reduced late activation to social status (vs neutral) words in the superior temporal cortex (STC) and medial prefrontal cortex (MPFC); whereas healthy youth did not show any significant differences between word types. Depressed youth also showed reduced late activation in the dorsolateral prefrontal cortex and fusiform gyrus to negative (vs positive) social status words; whereas healthy youth showed the opposite pattern. Finally, age was positively associated with MPFC activation to social status words. Findings suggest that hypoactivation in the "social cognitive brain network" might be implicated in altered interpersonal functioning in adolescent depression. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

    Science.gov (United States)

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

    2015-08-01

    Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (PDA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (PDA rats was significantly higher than that of DA.1U rats (PDA was greater than that in DA.1U rats (PDA rats was significantly higher than that in DA.1U rats in the respective experimental group (PDA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Childhood maltreatment and differential treatment response and recurrence in adult major depressive disorder.

    Science.gov (United States)

    Harkness, Kate L; Bagby, R Michael; Kennedy, Sidney H

    2012-06-01

    A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Participants included 203 adult outpatients with MDD (129 women; age 18-60). The design was a 16-week single-center randomized, open label trial of interpersonal psychotherapy, cognitive-behavioral therapy, or antidepressant medication, with a 12-month naturalistic follow-up, conducted at a university psychiatry center in Canada. The main outcome measure was Hamilton Depression Rating Scale scores at treatment end point. Childhood maltreatment was assessed at the completion of treatment using an interview-based contextual measure of childhood physical, sexual, and emotional abuse. Multiple imputation was adopted to estimate missing values. Patients with severe maltreatment were significantly less likely to respond to interpersonal psychotherapy than to cognitive-behavioral therapy or medication (OR = 3.61), whereas no differences among treatments were found in those with no history of maltreatment (ORs therapy than from interpersonal psychotherapy. However, these patients remain vulnerable to recurrence regardless of treatment modality.

  20. 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)

  1. 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.

  2. Genomic, RNAseq, and Molecular Modeling Evidence Suggests That the Major Allergen Domain in Insects Evolved from a Homodimeric Origin

    Science.gov (United States)

    Randall, Thomas A.; Perera, Lalith; London, Robert E.; Mueller, Geoffrey A.

    2013-01-01

    The major allergen domain (MA) is widely distributed in insects. The crystal structure of a single Bla g 1 MA revealed a novel protein fold in which the fundamental structure was a duplex of two subsequences (monomers), which had diverged over time. This suggested that the evolutionary origin of the MA structure may have been a homodimer of this smaller subsequence. Using publicly available genomic data, the distribution of the basic unit of this class of proteins was determined to better understand its evolutionary history. The duplication and divergence is examined at three distinct levels of resolution: 1) within the orders Diptera and Hymenoptera, 2) within one genus Drosophila, and 3) within one species Aedes aegypti. Within the family Culicidae, we have found two separate occurrences of monomers as independent genes. The organization of the gene family in A. aegypti shows a common evolutionary origin for its monomer and several closely related MAs. Molecular modeling of the A. aegypti monomer with the unique Bla g 1 fold confirms the distant evolutionary relationship and supports the feasibility of homodimer formation from a single monomer. RNAseq data for A. aegypti confirms that the monomer is expressed in the mosquito similar to other A. aegypti MAs after a blood meal. Together, these data support the contention that the detected monomer shares similar functional characteristics to related MAs in other insects. An extensive search for this domain outside of Insecta confirms that the MAs are restricted to insects. PMID:24253356

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

    Science.gov (United States)

    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…

  4. Molecular stress response pathways as the basis of hormesis

    DEFF Research Database (Denmark)

    Demirovic, Dino; de Toda, Irene Martinez; Rattan, Suresh

    2014-01-01

    There is now a large amount of data available for human beings showing positive hormetic effects of mild stresses from physical, chemical, nutritional and mental sources. However, these data are dispersed in the literature and not always interpreted as hormetic effects, thus restricting their full...... apprehension and application. A comprehensive discussion of the research, this book is composed of four sections: (1) History and terminology; (2) Evidence for hormesis in humans; (3) Molecular mechanisms of hormesis; and (4) Ethical and legal aspects, and risk assessment....

  5. 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...

  6. 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

  7. 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

  8. Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears.

    Science.gov (United States)

    Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk

    2008-07-01

    The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly

  9. Bacillus subtilis alters the proportion of major membrane phospholipids in response to surfactin exposure.

    Science.gov (United States)

    Uttlová, Petra; Pinkas, Dominik; Bechyňková, Olga; Fišer, Radovan; Svobodová, Jaroslava; Seydlová, Gabriela

    2016-12-01

    Surfactin, an anionic lipopeptide produced by Bacillus subtilis, is an antimicrobial that targets the cytoplasmic membrane. Nowadays it appears increasingly apparent that the mechanism of resistance against these types of antibiotics consists of target site modification. This prompted us to investigate whether the surfactin non-producing strain B. subtilis 168 changes its membrane composition in response to a sublethal surfactin concentration. Here we show that the exposure of B. subtilis to surfactin at concentrations of 350 and 650 μg/ml (designated as SF350 and SF650, respectively) leads to a concentration-dependent growth arrest followed by regrowth with an altered growth rate. Analysis of the membrane lipid composition revealed modifications both in the polar head group and the fatty acid region. The presence of either surfactin concentration resulted in a reduction in the content of the major membrane phospholipid phosphatidylglycerol (PG) and increase in phosphatidylethanolamine (PE), which was accompanied by elevated levels of phosphatidic acid (PA) in SF350 cultures. The fatty acid analysis of SF350 cells showed a marked increase in non-branched high-melting fatty acids, which lowered the fluidity of the membrane interior measured as the steady-state fluorescence anisotropy of DPH. The liposome leakage of carboxyfluorescein-loaded vesicles resembling the phospholipid composition of surfactin-adapted cells showed that the susceptibility to surfactin-induced leakage is strongly reduced when the PG/PE ratio decreases and/or PA is included in the target bilayer. We concluded that the modifications of the phospholipid content of B. subtilis cells might provide a self-tolerance of the membrane active surfactin. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ventilatory Response to Hypercapnia Predicts Dementia with Lewy Bodies in Late-Onset Major Depressive Disorder.

    Science.gov (United States)

    Takahashi, Sho; Mizukami, Katsuyoshi; Arai, Tetsuaki; Ogawa, Ryoko; Kikuchi, Norihiro; Hattori, Satoshi; Darby, David; Asada, Takashi

    2016-01-01

    Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB. Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD. Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123I-meta-iodobenzylguanidine scintigraphy. Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters. In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB.

  11. 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.

  12. Evaluation of molecular monitoring and response milestone of patients with chronic myeloid leukemia to tyrosine kinase inhibitors in Middle Euphrates of Iraq

    Directory of Open Access Journals (Sweden)

    Rahem M Rahem

    2016-01-01

    Conclusion: Most of our patients achieved major molecular response after 12 months of treatment with TKI according to the ELN guidelines that reflect proper management and regular follow-up of the patients by quantitative RT-PCR for the detection of BCR-ABL level.

  13. 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.

  14. Simulation analysis of the use of emergency resources during the emergency response to a major fire

    NARCIS (Netherlands)

    Zhou, Jianfeng; Reniers, G.L.L.M.E.

    2016-01-01

    During an emergency response to an accident or disaster, emergency response actions often need to use various emergency resources. The use of resources plays an important role in the successful implementation of emergency response, but there may be conflicts in the use of resources for emergency

  15. Nonlinear ultrafast optical response in organic molecular crystals

    Science.gov (United States)

    Rahman, Talat S.; Turkowski, Volodymyr; Leuenberger, Michael N.

    2012-02-01

    We analyze possible nonlinear excitonic effects in the organic molecule crystals by using a combined time-dependent DFT and many-body approach. In particular, we analyze possible effects of the time-dependent (retarded)interaction between different types of excitations, Frenkel excitons, charge transfer excitons and excimers, on the electric and the optical response of the system. We pay special attention to the case of constant electric field and ultrafast pulses, including that of four-wave mixing experiments. As a specific application we examine the optical excitations of pentacene nanocrystals and compare the results with available experimental data.[1] Our results demostrate that the nonlinear effects can play an important role in the optical response of these systems. [1] A. Kabakchiev, ``Scanning Tunneling Luminescence of Pentacene Nanocrystals'', PhD Thesis (EPFL, Lausanne, 2010).

  16. Human cervical cancer: therapeutic response assessment by innovative molecular strategies

    International Nuclear Information System (INIS)

    Nagarajan, Bala

    2016-01-01

    In Asia-Pacific region, the incidence of cancer of uterine cervix is high. Cancer is a multiple disease of multiple etiologies that has bearing on gene alteration that end result in abnormal cell dysfunction. We address the process interfacing infection, inflammation and oxidative damage that would lead to identify markers - to help improve patient management and bench to bedside. Radiation causes cell damage through production of reactive oxygen species. Radiation-induced DNA strand break is the primary mode of cell death. However, a secondary form of damage includes base modification or DNA adducts that are lethal on accumulation at higher levels. We analyzed polar and lipophilic adducts and found that the levels of adducts formed were independent of severity of disease status. 8 oxodG could be used as a marker to reflect patients potential to fix the lesion and response to radiation therapy. There was an increase in adduct levels in post treatment samples when compared to pre-RT, indicating radiation-induced DNA damage. Patients divided into two groups, high and low adduct formers, tend to show interindividual differences to fix the lesion that could be used to delineate radio-resistant or non-responding tumors. We have also looked at inflammatory cytokines, both by immunocytochemistry and m-RNA by RT-PCR through therapy, and generated definitive data that augur well with treatment response. The bottom line approach is prognostication and stratification. (author)

  17. 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.

  18. 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...

  19. 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

  20. 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

  1. Adiabatic Hamiltonian deformation, linear response theory, and nonequilibrium molecular dynamics

    International Nuclear Information System (INIS)

    Hoover, W.G.

    1980-01-01

    Although Hamiltonians of various kinds have previously been used to derive Green-Kubo relations for the transport coefficients, the particular choice described is uniquely related to thermodynamics. This nonequilibrium Hamiltonian formulation of fluid flow provides pedagogically simple routes to nonequilibrium fluxes and distribution functions, to theoretical understanding of long-time effects, and to new numerical methods for simulating systems far from equilibrium. The same methods are now being applied to solid-phase problems. At the relatively high frequencies used in the viscous fluid calculations described, solids typically behave elastically. Lower frequencies lead to the formation of dislocations and other defects, making it possible to study plastic flow. A property of the nonequilibrium equations of motion which might be profitably explored is their effective irreversibility. Because only a few particles are necessary to generate irreversible behavior, simulations using adiabatic deformations of the kind described here could perhaps elucidate the instability in the equations of motion responsible for irreversibility

  2. Molecular evaluation of vitamin D responsiveness of healthy young adults.

    Science.gov (United States)

    Seuter, Sabine; Virtanen, Jyrki K; Nurmi, Tarja; Pihlajamäki, Jussi; Mursu, Jaakko; Voutilainen, Sari; Tuomainen, Tomi-Pekka; Neme, Antonio; Carlberg, Carsten

    2017-11-01

    Vitamin D 3 has via its metabolites 25-hydroxyvitamin D 3 (25(OH)D 3 ) and 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) direct effects on the transcriptome and the epigenome of most human cells. In the VitDbol study we exposed 35 healthy young adults to an oral vitamin D 3 dose (2000μg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D 3 intake raised the average serum levels of both 25(OH)D 3 and 1,25(OH) 2 D 3 by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D 3 and 1,25(OH) 2 D 3 concentrations ranging from 277 to 1365. Interestingly, average serum parathyroid hormone (PTH) levels increased at day 1 by some 10% but then decreased within the following four weeks to levels 5% below baseline. In peripheral blood mononuclear cells (PBMCs) that were isolated at the same time points we determined vitamin D-modulated chromatin accessibility by FAIRE-qPCR at selected genomic loci. This method is well suited to evaluate both short-term and long-term in vivo effects of vitamin D on the epigenome of human subjects. The differential vitamin D responsiveness of the VitDbol study participants was determined via individual changes in their PTH levels or chromatin accessibility in relation to alterations in 25(OH)D 3 concentrations. This led to the segregation of the subjects into 14 high, 11 mid and 10 low responders. In summary, the vitamin D responsiveness classification provides additional information compared to a vitamin D status assessment based on single 25(OH)D 3 serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334). Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Molecular mechanisms of responses to radiation through protein kinase C

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo

    2005-01-01

    Described are the activation and cascade of the protein kinase C (PKC) which mediating the control of radiation-induced apoptosis. PKC is a family of c-, n- and a-subtypes and plays a major role in responding to the radiation exposure for DNA repair, cell cycle arrest and apoptosis. The author has conducted studies of mouse thymic lymphoma cells which have a property to respond even to low dose radiation, and has showed that, in the highly radiosensitive cell strain, 3SBH5 where apoptosis occurs in 50 and 90% post 0.5 and 2 Gy exposure, respectively, cPKC works as a surviving signal without intracellular movement after irradiation. In contrast, PKC has been alternatively shown to participate in apoptosis induction, showing that different enzyme species in the subtypes work specifically depending on passing time. Comparison with the radio-resistant cell strain, XR223, has revealed that the difference in the localization controls of PKCδ in the cell determines the radiosensitivity, however, the control mechanism is found to be separate from Atm pathway by which PKCδ is usually regulated. Recent studies have revealed that PKC performs the intracellular cross-talk in various phosphorylation cascades. Studies of PKC can be toward their uses for radiation effect assessment, radiotherapy and medicare for urgent exposure. (S.I.)

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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.

  7. Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression.

    Science.gov (United States)

    D'Urso, Giordano; Dell'Osso, Bernardo; Rossi, Rodolfo; Brunoni, Andre Russowsky; Bortolomasi, Marco; Ferrucci, Roberta; Priori, Alberto; de Bartolomeis, Andrea; Altamura, Alfredo Carlo

    2017-09-01

    Transcranial direct current stimulation (tDCS) is a promising neuromodulation intervention for poor-responding or refractory depressed patients. However, little is known about predictors of response to this therapy. The present study aimed to analyze clinical predictors of response to tDCS in depressed patients. Clinical data from 3 independent tDCS trials on 171 depressed patients (including unipolar and bipolar depression), were pooled and analyzed to assess predictors of response. Depression severity and the underlying clinical dimensions were measured using the Hamilton Depression Rating Scale (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis (bipolar/unipolar depression) were also investigated as predictors of response. Linear mixed models were fitted in order to ascertain which HDRS factors were associated with response to tDCS. Age, gender and diagnosis did not show any association with response to treatment. The reduction in HDRS scores after tDCS was strongly associated with the baseline values of "Cognitive Disturbances" and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild association with the response. Open-label design, the lack of control group, and minor differences in stimulation protocols. No differences in response to tDCS were found between unipolar and bipolar patients, suggesting that tDCS is effective for both conditions. "Cognitive disturbance", "Retardation", and "Anxiety/Somatization", were identified as potential clinical predictors of response to tDCS. These findings point to the pre-selection of the potential responders to tDCS, therefore optimizing the clinical use of this technique and the overall cost-effectiveness of the psychiatric intervention for depressed patients. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Molecular events basic to cellular radiation response. Progress report

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    1974-01-01

    Work during the past year has been focused on three areas related to the cellular effects of radiation. Radiation effects on RNA and the regulation of gene expression and amino acid-nucleic acid interactions were studied. Studies on the radiation response of RNA in growing and confluent cells were continued. We have derived radiation survival curves and demonstrated repair of potentially lethal damage in 3T3 cells. Studies of giant cell formation and turnover of ribosomal RNA in irradiated cells has demonstrated differences in growing and confluent cells. We have sought evidence consistent with our hypothesis for regulation of eukaryotic gene expression with segments of RNA reutilized to prime new RNA synthesis. Data derived from the turnover of ribosomal RNA and the methylation pattern of ribosomal RNA during turnover are consistent with the possibility that a segment of 18s ribosomal RNA is being conserved during new RNA synthesis. We were unable to show reutilization of the 5' trinucleotide of 18s and 28s ribosomal RNA but did find a ribonuclease resistant oligonucleotide in 18s RNA which appeared to be reutilized. In studies of amino acid nucleic-acid interactions using nuclear magnetic resonance spectroscopy we have been able to successfully synthesize an amidate and begin an examination of the intramolecular interactions. We have also studied intermolecular interactions betweentryptophan and nucleoside monophosphates and found upfield shifts which provide evidence for preferential stacking of the 6-membered ring of tryptophan with adenine and evidence for specific geometry of interactions of tryptophan with cytosine. (U.S.)

  10. 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.

  11. 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

  12. 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.

  13. Responses of garlic bulbs to gamma irradiation. Changes in major amino acids

    International Nuclear Information System (INIS)

    Parolo, Maria E.; Orioli, Gustavo A.; Croci, Clara A.

    1997-01-01

    Studies were conducted to provide information about the amino acids composition of garlic bulbs cv Colorado and to determinate the effect of a dose of 60 Gy of gamma rays on the behavior of the major free amino acids in relation to sprout growth radioinhibition. TLC and HPLC were used for identification and quantification of free amino acids. Eighteen free amino acids were identified in both parts of garlic bulbs: alanine, glycine, proline, methionine, serine, phenylalanine, aspartic acid, glutamic acid, lysine, glutamine, arginine, tyrosine, threonine, cystine, cysteine, leucine + isoleucine and asparagine. In the inner sprout the major amino acids founded were: glutamine, glutamic acid, threonine, asparagine, cystine, cysteine and methionine; in the storage leaf also arginine was also predominant. In general concentration of amino acids appeared to less affected by irradiation in the storage leaf that in the inner sprout. An increase in the short time post-irradiation in glutamine, glutamic acid, asparagine, theorine and methionine was observed. Sprout grouth radioinhibition was evident about 70 days after treatment and was preceded by a decrease in the major amino acids except methionine. It appears that concentration of same major amino acidscan be used as monitors of radioinhibition process in inner sprout of garlic. (author). 15 refs., 8 figs

  14. No effect of melatonin to modify surgical-stress response after major vascular surgery

    DEFF Research Database (Denmark)

    Kücükakin, B.; Wilhelmsen, M.; Lykkesfeldt, Jens

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  15. 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...

  16. 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

  17. An investigation of major influences on the seismic response of APR1400 reactor vessel internals - 15145

    International Nuclear Information System (INIS)

    Byun, Y.J.; Kim, J.G.; Sung, K.K.; Lee, D.H.

    2015-01-01

    This paper deals with 3 topics concerning the APR1400 reactor vessel internals (RVI) seismic analysis: nonlinear problems, approaches to account for uncertainties of seismic model, and dynamic responses to various seismic excitations. First, the noticeable nonlinear characteristics of the RVI seismic model are discussed, and the modeling methods for properly simulating the nonlinear behaviors of RVI under seismic loads are presented. By applying these methods to the seismic model, the seismic analysis can correctly predict the dynamic response of RVI. Next, two approaches to account for the uncertainties of seismic model are evaluated: the time history broadening method, and the sensitivity analysis based on NUREG-0800, Section 4.2, Appendix A. From the evaluation results, it is confirmed that the time history broadening method employed in the seismic analysis of APR1400 RVI sufficiently accounts for the uncertainty of seismic model. Finally, the response characteristics of APR1400 RVI to various seismic excitations are investigated. The seismic excitations corresponding to various soil profiles, including the effects of cracked and un-cracked concrete stiffness on the reactor containment building structure, are used as forcing functions. From this study, the effects of various site conditions on the dynamic response of APR1400 RVI are identified. As a result, the enveloped seismic responses obtained from this study will contribute to the development of RVI seismic design that covers a wide range of potential site conditions. (authors)

  18. 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

  19. 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

  20. Race, Genetic Ancestry and Response to Antidepressant Treatment for Major Depression

    Science.gov (United States)

    Murphy, Eleanor; Hou, Liping; Maher, Brion S; Woldehawariat, Girma; Kassem, Layla; Akula, Nirmala; Laje, Gonzalo; McMahon, Francis J

    2013-01-01

    The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study revealed poorer antidepressant treatment response among black compared with white participants. This racial disparity persisted even after socioeconomic and baseline clinical factors were taken into account. Some studies have suggested genetic contributions to this disparity, but none have attempted to disentangle race and genetic ancestry. Here we used genome-wide single-nucleotide polymorphism (SNP) data to examine independent contributions of race and genetic ancestry to citalopram response. Secondary data analyses included 1877 STAR*D participants who completed an average of 10 weeks of citalopram treatment and provided DNA samples. Participants reported their race as White (n=1464), black (n=299) or other/mixed (n=114). Genetic ancestry was estimated by multidimensional scaling (MDS) analyses of about 500 000 SNPs. Ancestry proportions were estimated by STRUCTURE. Structural equation modeling was used to examine the direct and indirect effects of observed and latent predictors of response, defined as change in the Quick Inventory of Depressive Symptomatology (QIDS) score from baseline to exit. Socioeconomic and baseline clinical factors, race, and anxiety significantly predicted response, as previously reported. However, direct effects of race disappeared in all models that included genetic ancestry. Genetic African ancestry predicted lower treatment response in all models. Although socioeconomic and baseline clinical factors drive racial differences in antidepressant response, genetic ancestry, rather than self-reported race, explains a significant fraction of the residual differences. Larger samples would be needed to identify the specific genetic mechanisms that may be involved, but these findings underscore the importance of including more African-American patients in drug trials. PMID:23827886

  1. Coordinating management disciplines to build operational resilience in response to a major crisis situation.

    Science.gov (United States)

    Drachal, Marcin

    2017-01-01

    Using case studies of the Ebola outbreak in Western Africa in 2014, and the terrorist attacks in Paris and Brussels in 2015 and 2016 respectively, this paper demonstrates how various resilience-related corporate functions contributed to effective crisis response. This paper describes the logical order of actions taken in each of the cases, and how the organisation prioritised its assets and coordinated activities to ensure the response was adequate, efficient and timely. The article demonstrates how business continuity, physical security, threat management, security intelligence and incident management worked together to support the organisation's crisis management structures in complex crisis situations.

  2. Personality predicts spatial responses to food manipulations in free-ranging great tits (Parus major)

    OpenAIRE

    van Overveld, Thijs; Matthysen, Erik

    2009-01-01

    Personality differences measured under standardized lab-conditions are assumed to reflect differences in the way individuals cope with spatio-temporal changes in their natural environment, but few studies have examined how these are expressed in the field. We tested whether exploratory behaviour in a novel environment predicts how free-living individual great tits (Parus major) react to a change in food supply. We temporarily removed food at feeding stations during two summers and recorded th...

  3. [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.

  4. 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

  5. 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

  6. A New Approach to Teaching Science to Elementary Education Majors in Response to the NGSS

    Science.gov (United States)

    Brevik, C.; Daniels, L.; McCoy, C.

    2015-12-01

    The Next Generation Science Standards (NGSS) place an equal emphasis on science process skills and science content. The goal is to have K-12 students "doing" science, not just "learning about" science. However, most traditional college science classes for elementary education majors place a much stronger emphasis on science content knowledge with the hands-on portion limited to a once-a-week lab. The two models of instruction are not aligned. The result is that many elementary school teachers are unprepared to offer interactive science with their students. Without additional coaching, many teachers fall back on the format they learned in college - lecture, handouts, homework. If we want teachers to use more hands-on methods in the classroom, these techniques should be taught to elementary education majors when they are in college. Dickinson State University has begun a collaboration between the Teacher Education Department and the Department of Natural Sciences. The physical science course for elementary education majors has been completely redesigned to focus equally on the needed science content and the science process skills emphasized by the NGSS. The format of the course has been adjusted to more closely mirror a traditional K-5 classroom; the course meets for 50 minutes five days a week. A flipped-classroom model has been adopted to ensure no content is lost, and hands-on activities are done almost every day as new concepts are discussed. In order to judge the effectiveness of these changes, a survey tool was administered to determine if there was a shift in the students' perception of science as an active instead of a passive field of study. The survey also measured the students' comfort-level in offering a hands-on learning environment in their future classrooms and their confidence in their ability to effectively teach science concepts to elementary students. Results from the first year of the study will be presented.

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

    Science.gov (United States)

    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...

  8. Major structural response methods used in the seismic safety margins research program

    International Nuclear Information System (INIS)

    Chou, C.K.; Lo, T.; Vagliente, V.

    1979-01-01

    In order to evaluate the conservatisms in present nuclear power plant seismic safety requirements, a probabilistic based systems model is being developed. This model will also be used to develop improved requirements. In Phase I of the Seismic Safety Margins Research Program (SSMRP), this methodology will be developed for a specific nuclear power plant and used to perform probabilistic sensitivity studies to gain engineering insights into seismic safety requirements. Random variables in the structural response analysis area, or parameters which cause uncertainty in the response, are discussed and classified into three categories; i.e., material properties, structural dynamic characteristics and related modeling techniques, and analytical methods. The sensitivity studies are grouped into two categories; deterministic and probabilistic. In a system analysis, transfer functions in simple form are needed since there are too many responses which have to be calculated in a Monte Carlo simulation to use the usual straightforward calculation approach. Therefore, the development of these simple transfer functions is one of the important tasks in SSMRP. Simplified as well as classical transfer functions are discussed

  9. 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.

  10. Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

    Science.gov (United States)

    Kolb, Jennifer M; Flack, Kathryn Friedman; Chatterjee-Murphy, Prapti; Desai, Jay; Wallentin, Lars C; Ezekowitz, Michael; Connolly, Stuart; Reilly, Paul; Brueckmann, Martina; Ilgenfritz, John; Aisenberg, James

    2018-03-27

    Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

  11. 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

  12. Enhanced subgenual cingulate response to altruistic decisions in remitted major depressive disorder

    Directory of Open Access Journals (Sweden)

    Erdem Pulcu

    2014-01-01

    Conclusions: We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called “warm glow” of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.

  13. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

    Science.gov (United States)

    Anahtar, Melis N; Byrne, Elizabeth H; Doherty, Kathleen E; Bowman, Brittany A; Yamamoto, Hidemi S; Soumillon, Magali; Padavattan, Nikita; Ismail, Nasreen; Moodley, Amber; Sabatini, Mary E; Ghebremichael, Musie S; Nusbaum, Chad; Huttenhower, Curtis; Virgin, Herbert W; Ndung'u, Thumbi; Dong, Krista L; Walker, Bruce D; Fichorova, Raina N; Kwon, Douglas S

    2015-05-19

    Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    International Nuclear Information System (INIS)

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  15. A review of major factors influencing plant responses to recreation impacts

    Science.gov (United States)

    Kuss, Fred R.

    1986-09-01

    This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

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

    Science.gov (United States)

    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).

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

    Science.gov (United States)

    Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

    2002-09-01

    We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

  19. 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

  20. 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.

  1. 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.

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

    Science.gov (United States)

    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.

  3. 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

  4. A decision support system for emergency response to major nuclear accidents

    International Nuclear Information System (INIS)

    Papazoglou, I.A.; Christou, M.D.

    1997-01-01

    A methodology for the optimization of the short-term emergency response in the event of a nuclear accident is presented. The method seeks an optimum combination of protective actions in the presence of a multitude of conflicting objectives and under uncertainty. Conflicting objectives arise in the attempt to minimize simultaneously the potential adverse effects of an accident and the associated socioeconomic impacts. Additional conflicting objectives arise whenever an emergency plan tends to decrease a particular health effect, such as acute deaths, while it increases another, such as latent deaths. The uncertainty is due to the multitude of possible accident scenarios and their respective probability of occurrence, the stochastic variability in the weather conditions, and the variability and/or lack of knowledge of the parameters of the risk assessment models. A multiobjective optimization approach is adopted. An emergency protection plan consists of defining a protective action at each spatial cell around the plant. Three criteria are used as the objective functions of the problem, namely, acute fatalities, latent effects, and socioeconomic cost. The optimization procedure defines the efficient frontier, i.e., all emergency plans that are not dominated by another in all three criteria. No value trade-offs are necessary up to this point. The most preferred emergency plan is then chosen among the set of efficient plans. Finally, the methodology is integrated into a computerized decision support system, and its use is demonstrated in a realistic application

  5. Workload differences across command levels and emergency response organizations during a major joint training exercise.

    Science.gov (United States)

    Prytz, Erik G; Rybing, Jonas; Jonson, Carl-Oscar

    2016-01-01

    This study reports on an initial test using a validated workload measurement method, the NASA Task Load Index (TLX), as an indicator of joint emergency exercise effectiveness. Prior research on emergency exercises indicates that exercises must be challenging, ie, result in high workload, to be effective. However, this is often problematic with some participants being underloaded and some overloaded. The NASA TLX was used to test for differences in workload between commanders and subordinates and among three different emergency response organizations during a joint emergency exercise. Questionnaire-based evaluation with professional emergency responders. The study was performed in conjunction with a large-scale interorganizational joint emergency exercise in Sweden. A total of 20 participants from the rescue services, 12 from the emergency medical services, and 12 from the police participated in the study (N=44). Ten participants had a command-level role during the exercise and the remaining 34 were subordinates. The main outcome measures were the workload subscales of the NASA TLX: mental demands, physical demands, temporal demands, performance, effort, and frustration. The results showed that the organizations experienced different levels of workload, that the commanders experienced a higher workload than the subordinates, and that two out of three organizations fell below the twenty-fifth percentile of average workload scores compiled from 237 prior studies. The results support the notion that the NASA TLX could be a useful complementary tool to evaluate exercise designs and outcomes. This should be further explored and verified in additional studies.

  6. Frequency Domain Response at Pacific Coast Harbors to Major Tsunamis of 2005-2011

    Science.gov (United States)

    Xing, Xiuying; Kou, Zhiqing; Huang, Ziyi; Lee, Jiin-Jen

    2013-06-01

    Tsunamis waves caused by submarine earthquake or landslide might contain large wave energy, which could cause significant human loss and property damage locally as well as in distant region. The response of three harbors located at the Pacific coast (i.e. Crescent City Harbor, Los Angeles/Long Beach Port, and San Diego Harbor) to six well-known tsunamis events generated (both near-field and far-field) between 2005 and 2011 are examined and simulated using a hybrid finite element numerical model in frequency domain. The model incorporated the effects of wave refraction, wave diffraction, partial wave reflection from boundaries, entrance and bottom energy dissipation. It can be applied to harbor regions with arbitrary shapes and variable water depth. The computed resonant periods or modes of oscillation for three harbors are in good agreement with the energy spectral analysis of the time series of water surface elevations recorded at tide gauge stations inside three harbors during the six tsunamis events. The computed wave induced currents based on the present model are also in qualitative agreement with some of the reported eye-witness accounts absence of reliable current data. The simulated results show that each harbor responded differently and significantly amplified certain wave period(s) of incident wave trains according to the shape, topography, characteristic dimensions and water depth of the harbor basins.

  7. Two Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment Goal

    Science.gov (United States)

    Huijgen, Roeland; Kindt, Iris; Verhoeven, Sjoerd B. J.; Sijbrands, Eric J. G.; Vissers, Maud N.; Kastelein, John J. P.; Hutten, Barbara A.

    2010-01-01

    Background The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings In 2008, we sent questionnaires to all subjects (aged 18–65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through genetic cascade screening. The attained LDL-C levels were lower than those reported in previous surveys on medication use in FH, which could reflect the effect of more stringent lipid target levels. However, only a minority of the medication users reached the LDL-C target. PMID:20169164

  8. Online molecular characterization of fine particulate matter in Port Angeles, WA: Evidence for a major impact from residential wood smoke

    Science.gov (United States)

    Gaston, Cassandra J.; Lopez-Hilfiker, Felipe D.; Whybrew, Lauren E.; Hadley, Odelle; McNair, Fran; Gao, Honglian; Jaffe, Daniel A.; Thornton, Joel A.

    2016-08-01

    We present on-line molecular composition measurements of wintertime particulate matter (PM) during 2014 using an iodide-adduct high-resolution, time-of-flight chemical ionization mass spectrometer (HR-TOF-CIMS) coupled to a Filter Inlet for Gases and AEROsols (FIGAERO). These measurements were part of an intensive effort to characterize PM in the region with a focus on ultrafine particle sources. The technique was used to detect and quantify different classes of wood burning tracers, including levoglucosan, methoxyphenols, and nitrocatechols, among other compounds in near real-time. During the campaign, particulate mass concentrations of compounds with the same molecular composition as levoglucosan ranged from 0.002 to 19 μg/m3 with a median mass concentration of 0.9 μg/m3. Wood burning markers, in general, showed a strong diurnal pattern peaking at night and in the early morning. This diurnal profile combined with cold, stagnant conditions, wind directions from predominantly residential areas, and observations of lower combustion efficiency at night support residential wood burning as a dominant source of wintertime PM in Port Angeles. This finding has implications for improving wintertime air quality in the region by encouraging the use of high efficiency wood-burning stoves or other cleaner home heating options throughout the relevant domain.

  9. 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

  10. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  14. 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.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. 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.

  18. 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

  19. 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

  20. An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil.

    Science.gov (United States)

    Amaral, Amanda Gm; Oliveira, Isabele B; Carneiro, Diego C; Alcantara, Luiz Cj; Monteiro-Cunha, Joana P

    2017-06-01

    The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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

  5. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  6. Response of Major Cities

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Beijing:trading in future housing down by 40 percent Two weeks before and after the promulgation of the new policies (six measures), trade in Beijing's real estate market dropped sharply. Statistics from www.bjfdc.gov.cn show that on June 1, 2006, only 325 apartments were sold in future housing trade, but a week before the number was 519. In the next three days, although there was a

  7. The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of Polistes dominula venom.

    Science.gov (United States)

    Schiener, Maximilian; Hilger, Christiane; Eberlein, Bernadette; Pascal, Mariona; Kuehn, Annette; Revets, Dominique; Planchon, Sébastien; Pietsch, Gunilla; Serrano, Pilar; Moreno-Aguilar, Carmen; de la Roca, Federico; Biedermann, Tilo; Darsow, Ulf; Schmidt-Weber, Carsten B; Ollert, Markus; Blank, Simon

    2018-01-22

    Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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.

  11. Stress response and communication in surgeons undergoing training in endoscopic management of major vessel hemorrhage: a mixed methods study.

    Science.gov (United States)

    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.

  12. 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

  13. An adenoviral vector expressing lipoprotein A, a major antigen of Mycoplasma mycoides subspecies mycoides, elicits robust immune responses in mice.

    Science.gov (United States)

    Carozza, Marlène; Rodrigues, Valérie; Unterfinger, Yves; Galea, Sandra; Coulpier, Muriel; Klonjkowski, Bernard; Thiaucourt, François; Totté, Philippe; Richardson, Jennifer

    2015-01-01

    Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

    Science.gov (United States)

    Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J

    2017-06-01

    Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review.

    Science.gov (United States)

    Johnsen, Anne Siri; Fattah, Sabina; Sollid, Stephen J M; Rehn, Marius

    2016-02-09

    This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. Early prehospital phase of a major incident. Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and 'major incidents' to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. CRD42013004473. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. 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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Evolutionary responses by native species to major anthropogenic changes to their ecosystems: Pacific salmon in the Columbia River hydropower system.

    Science.gov (United States)

    Waples, Robin S; Zabel, Richard W; Scheuerell, Mark D; Sanderson, Beth L

    2008-01-01

    The human footprint is now large in all the Earth's ecosystems, and construction of large dams in major river basins is among the anthropogenic changes that have had the most profound ecological consequences, particularly for migratory fishes. In the Columbia River basin of the western USA, considerable effort has been directed toward evaluating demographic effects of dams, yet little attention has been paid to evolutionary responses of migratory salmon to altered selective regimes. Here we make a first attempt to address this information gap. Transformation of the free-flowing Columbia River into a series of slack-water reservoirs has relaxed selection for adults capable of migrating long distances upstream against strong flows; conditions now favour fish capable of migrating through lakes and finding and navigating fish ladders. Juveniles must now be capable of surviving passage through multiple dams or collection and transportation around the dams. River flow patterns deliver some groups of juvenile salmon to the estuary later than is optimal for ocean survival, but countervailing selective pressures might constrain an evolutionary response toward earlier migration timing. Dams have increased the cost of migration, which reduces energy available for sexual selection and favours a nonmigratory life history. Reservoirs are a benign environment for many non-native species that are competitors with or predators on salmon, and evolutionary responses are likely (but undocumented). More research is needed to tease apart the relative importance of evolutionary vs. plastic responses of salmon to these environmental changes; this research is logistically challenging for species with life histories like Pacific salmon, but results should substantially improve our understanding of key processes. If the Columbia River is ever returned to a quasinatural, free-flowing state, remaining populations might face a Darwinian debt (and temporarily reduced fitness) as they struggle to

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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...

  7. 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....

  8. 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.

  9. 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.

  10. A machine learning approach using EEG data to predict response to SSRI treatment for major depressive disorder.

    Science.gov (United States)

    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.

  11. 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

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

    Science.gov (United States)

    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).

  13. 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).

  14. TaWRKY68 responses to biotic stresses are revealed by the orthologous genes from major cereals

    Directory of Open Access Journals (Sweden)

    Bo Ding

    2014-01-01

    Full Text Available WRKY transcription factors have been extensively characterized in the past 20 years, but in wheat, studies onWRKY genes and their function are lagging behind many other species. To explore the function of wheat WRKY genes, we identified a TaWRKY68 gene from a common wheat cultivar. It encodes a protein comprising 313 amino acids which harbors 19 conserved motifs or active sites. Gene expression patterns were determined by analyzing microarray data of TaWRKY68 in wheat and of orthologous genes from maize, rice and barley using Genevestigator. TaWRKY68 orthologs were identified and clustered using DELTA-BLAST and COBALT programs available at NCBI. The results showed that these genes, which are expressed in all tissues tested, had relatively higher levels in the roots and were up-regulated in response to biotic stresses. Bioinformatics results were confirmed by RT-PCR experiments using wheat plants infected by Agrobacterium tumefaciens and Blumeria graminis, or treated with Deoxynivalenol, a Fusarium graminearum-induced mycotoxin in wheat or barley. In summary,TaWRKY68 functions differ during plant developmental stages and might be representing a hub gene function in wheat responses to various biotic stresses. It was also found that including data from major cereal genes in the bioinformatics analysis gave more accurate and comprehensive predictions of wheat gene functions.

  15. A comparison of placebo response with major depressive disorder in patients recruited through newspaper advertising versus consultation referrals.

    Science.gov (United States)

    Miller, C A; Hooper, C L; Bakish, D

    1997-01-01

    Recent evidence indicates few differences between patients recruited through advertising and by consultation referral, and there is some suggestion that those recruited through advertising are more representative of the target community population. However little has been reported on differences in placebo response and compliance in these two patient groups. We conducted a retrospective chart review of 49 patients with major depressive disorder (MDD), recruited through advertising or consultation, randomized to placebo in five clinical trials. Variables included demographics, clinical history, efficacy, compliance, and completion data. Homogeneity was demonstrated for most variables. Differences in placebo groups included significantly lower Hamilton Rating Scale for Depression (HAM-D) scores for the advertisement group throughout the trials. Advertisement patients were also more likely to be early placebo responders and in remission at Days 14 and 28. No differences were found in completion rates or reasons for early termination. Compliance was excellent for both groups. Early placebo response of the advertisement group reinforces the need for trials of at least 8 weeks. In addition, consultation patients may have a more severe illness and be treatment resistant, suggesting they are less generalizable to community practice populations.

  16. Iron oxide nanoparticles induced alterations in haematological, biochemical and ionoregulatory responses of an Indian major carp Labeo rohita

    Energy Technology Data Exchange (ETDEWEB)

    Saravanan, M.; Suganya, R.; Ramesh, M., E-mail: mathanramesh@yahoo.com; Poopal, R. K. [Bharathiar University, Unit of Toxicology, Department of Zoology, School of Life Sciences (India); Gopalan, N. [Bharathiar University, DRDO-BU (India); Ponpandian, N. [Bharathiar University, Department of Nanoscience and Technology (India)

    2015-06-15

    The wide use of iron oxide nanoparticles (Fe{sub 2}O{sub 3} NPs) in various applications has raised great concerns worldwide. In this work, we measured the potential harmful effects of Fe{sub 2}O{sub 3} NP (<50 nm) at concentrations of 1 and 25 mg/L on haematological, biochemical, and ionoregulatory responses in an Indian major carp, Labeo rohita for a short-term period of 96 h. The results revealed significant (P < 0.05) decreases in haemoglobin, haematocrit, mean cellular volume, mean cellular haemoglobin, protein, sodium (Na{sup +}), potassium (K{sup +}), chloride (Cl{sup −}) and gill Na{sup +}/K{sup +}-ATPase levels in both the concentrations. White blood cell, mean cellular haemoglobin concentration and glucose levels were significantly (P < 0.05) increased in response to both concentrations during the study period. However, no significant changes in red blood cell count and gill Na{sup +}/K{sup +}-ATPase (25 mg/L) activity were noticed compared to those of the respective control groups. Based on this study, it was found that the Fe{sub 2}O{sub 3} NPs do have prominent effects on freshwater fish L. rohita. Our data suggest that the alterations of these parameters can be used as nonspecific biomarkers to monitor the environmental risks arising from nanoparticles in aquatic ecosystem and also regulate the use, production and release of nanoparticles.

  17. Perseverative thought: a robust predictor of response to emotional challenge in generalized anxiety disorder and major depressive disorder.

    Science.gov (United States)

    Ruscio, Ayelet Meron; Seitchik, Allison E; Gentes, Emily L; Jones, Jason D; Hallion, Lauren S

    2011-12-01

    Generalized anxiety disorder (GAD) and major depressive disorder (MDD) frequently co-occur, yet the reasons for their comorbidity remain poorly understood. In the present experiment, we tested whether a tendency to engage in negative, repetitive thinking constitutes a common risk process for the two disorders. A mixed sample of adults with comorbid GAD-MDD (n=50), GAD only (n=35), MDD only (n=34), or no lifetime psychopathology (n=35) was administered noncontingent failure and success feedback on consecutive performance tasks. Perseverative thought (PT), measured by negative thought intrusions during a baseline period of focused breathing, emerged as a powerful prospective predictor of responses to this experimental challenge. Participants reporting more frequent negative thought intrusions at baseline, irrespective of thought content or diagnostic status, exhibited a stronger negative response to failure that persisted even after subsequent success. Higher PT over the course of the experiment was associated with later behavioral avoidance, with negative affect and other traits closely linked to anxiety and depression, and with the presence and severity of GAD and MDD. These findings provide evidence for a broadly-defined PT trait that is shared by GAD and MDD and contributes to adverse outcomes in these disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder.

    Science.gov (United States)

    Philip, Noah S; Barredo, Jennifer; van 't Wout-Frank, Mascha; Tyrka, Audrey R; Price, Lawrence H; Carpenter, Linda L

    2018-02-01

    Repetitive transcranial magnetic stimulation (TMS) therapy can modulate pathological neural network functional connectivity in major depressive disorder (MDD). Posttraumatic stress disorder is often comorbid with MDD, and symptoms of both disorders can be alleviated with TMS therapy. This is the first study to evaluate TMS-associated changes in connectivity in patients with comorbid posttraumatic stress disorder and MDD. Resting-state functional connectivity magnetic resonance imaging was acquired before and after TMS therapy in 33 adult outpatients in a prospective open trial. TMS at 5 Hz was delivered, in up to 40 daily sessions, to the left dorsolateral prefrontal cortex. Analyses used a priori seeds relevant to TMS, posttraumatic stress disorder, or MDD (subgenual anterior cingulate cortex [sgACC], left dorsolateral prefrontal cortex, hippocampus, and basolateral amygdala) to identify imaging predictors of response and to evaluate clinically relevant changes in connectivity after TMS, followed by leave-one-out cross-validation. Imaging results were explored using data-driven multivoxel pattern activation. More negative pretreatment connectivity between the sgACC and the default mode network predicted clinical improvement, as did more positive amygdala-to-ventromedial prefrontal cortex connectivity. After TMS, symptom reduction was associated with reduced connectivity between the sgACC and the default mode network, left dorsolateral prefrontal cortex, and insula, and reduced connectivity between the hippocampus and the salience network. Multivoxel pattern activation confirmed seed-based predictors and correlates of treatment outcomes. These results highlight the central role of the sgACC, default mode network, and salience network as predictors of TMS response and suggest their involvement in mechanisms of action. Furthermore, this work indicates that there may be network-based biomarkers of clinical response relevant to these commonly comorbid disorders

  20. Striatal dopamine D2/3 receptor-mediated neurotransmission in major depression: Implications for anhedonia, anxiety and treatment response.

    Science.gov (United States)

    Peciña, Marta; Sikora, Magdalena; Avery, Erich T; Heffernan, Joseph; Peciña, Susana; Mickey, Brian J; Zubieta, Jon-Kar

    2017-10-01

    Dopamine (DA) neurotransmission within the brain's reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D 2/3 receptor-selective radiotracer [ 11 C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC). We investigated the relationship between D 2/3 receptor availability and baseline measures of depression severity, anxiety, anhedonia, and cognitive and pharmacological mechanisms of treatment response. We found that, compared to controls, patients with depression showed greater D 2/3 receptor availability in several striatal regions, including the bilateral ventral pallidum/nucleus accumbens (vPAL/NAc), and the right ventral caudate and putamen. In the depressed sample, D 2/3 receptor availability in the caudal portion of the ventral striatum (NAc/vPAL) correlated with higher anxiety symptoms, whereas D 2/3 receptor availability in the rostral area of the ventral striatum correlated negatively with the severity of motivational anhedonia. Finally, MDD non-remitters showed greater baseline anxiety, greater D 2/3 availability in the NAc/vPAL, and greater placebo-induced DA release in the bilateral NAc. Our results demonstrate abnormally high D 2/3 receptor availability in the ventral striatum of patients with MDD, which seem to be associated with comorbid anxiety symptoms and lack of response to antidepressants. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  1. 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.

  2. 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

  3. 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)

  4. Molecular Modeling and Structural Stability of Wild-Type and Mutant CYP51 from Leishmania major: In Vitro and In Silico Analysis of a Laboratory Strain

    Directory of Open Access Journals (Sweden)

    Masoud Keighobadi

    2018-03-01

    Full Text Available Cutaneous leishmaniasis is a neglected tropical disease and a major public health in the most countries. Leishmania major is the most common cause of cutaneous leishmaniasis. In the Leishmania parasites, sterol 14α-demethylase (CYP51, which is involved in the biosynthesis of sterols, has been identified as an attractive target for development of new therapeutic agents. In this study, the sequence and structure of CYP51 in a laboratory strain (MRHO/IR/75/ER of L. major were determined and compared to the wild-type strain. The results showed 19 mutations including seven non-synonymous and 12 synonymous ones in the CYP51 sequence of strain MRHO/IR/75/ER. Importantly, an arginine to lysine substitution at position of 474 resulted in destabilization of CYP51 (ΔΔG = 1.17 kcal/mol in the laboratory strain; however, when the overall effects of all substitutions were evaluated by 100 ns molecular dynamics simulation, the final structure did not show any significant changes (p-value < 0.05 in stability parameter of the strain MRHO/IR/75/ER compared to the wild-type protein. The energy level for the CYP51 of wild-type and MRHO/IR/75/ER strain were −40,027.1 and −39,706.48 Kcal/mol respectively. The overall Root-mean-square deviation (RMSD deviation between two proteins was less than 1 Å throughout the simulation and Root-mean-square fluctuation (RMSF plot also showed no substantial differences between amino acids fluctuation of the both protein. The results also showed that, these mutations were located on the protein periphery that neither interferes with protein folding nor with substrate/inhibitor binding. Therefore, L. major strain MRHO/IR/75/ER is suggested as a suitable laboratory model for studying biological role of CYP51 and inhibitory effects of sterol 14α-demethylase inhibitors.

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

    Science.gov (United States)

    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

  6. 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

  7. 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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Kassiani Theodoraki

    2014-01-01

    Full Text Available 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 below 7.7 g dL−1 or 9.9 g dL−1, respectively. In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNFα. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82±29.07 vs. 15.83±13.22 pg mL−1, P<0.05. Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r2=0.38, P=0.032, r2=0.52, P=0.007, and r2=0.68, P<0.001, respectively. IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525.

  10. 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.

  11. Psychometric properties of the Ruminative Response Scale-short form in a clinical sample of patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Parola N

    2017-05-01

    Full Text Available Nathalie Parola,1,2,* Xavier Yves Zendjidjian,1,3,* Marine Alessandrini,1 Karine Baumstarck,1 Anderson Loundou,1 Guillaume Fond,4,5 Fabrice Berna,4,6 Christophe Lançon,1–3 Pascal Auquier,1 Laurent Boyer1 1Public Health, Chronic Diseases and Quality of Life – Research Unit EA 3279, Aix-Marseille University, Marseille, 2Department of Psychiatry, Sainte-Marguerite University Hospital, Marseille, 3Department of Psychiatry, La Conception University Hospital, Marseille, 4Fondation FondaMental, Créteil, 5Department of Psychiatry and Addictology, Henri Mondor University Hospital, INSERM U955, Eq 15 Genetic Psychiatry and Psychopathology, Paris Est-Créteil University, Créteil, 6Department of Psychiatry, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg University Hospital, Strasbourg, France *These authors contributed equally to this work Background: The Ruminative Response Scale (RRS-short form is one of the most widely used measures of rumination, comprising ten items and two components: reflection and brooding. The aim of this study was to investigate RRS validity and reliability in a clinical sample of French patients with major depressive disorder (MDD.Subjects and methods: Outpatients with a DSM-IV-TR diagnosis of MDD were recruited from a public academic hospital in France. Depressive symptoms were evaluated by the Beck Depression Inventory, anxiety by the State-Trait Anxiety Inventory – state scale, and quality of life by the 36-Item Short Form Health Survey (SF-36 questionnaire. Confirmatory factor analyses, item-dimension correlations, Cronbach’s α-coefficients, Rasch statistics, and external validity were tested. Differential item functioning analyses were performed for sex.Results: A total of 109 patients participated. The final reflection–brooding two-factor model of the RRS showed a good fit (root-mean-square error of approximation 0.041, comparative fit index 0.987, standardized root

  12. 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

  13. 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.

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

    Science.gov (United States)

    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.

  15. Inducible Major Vault Protein Plays a Pivotal Role in Double-Stranded RNA- or Virus-Induced Proinflammatory Response.

    Science.gov (United States)

    Peng, Nanfang; Liu, Shi; Xia, Zhangchuan; Ren, Sheng; Feng, Jian; Jing, Mingzhen; Gao, Xin; Wiemer, Erik A C; Zhu, Ying

    2016-03-15

    Pathogen invasion triggers robust antiviral cytokine production via different transcription factor signaling pathways. We have previously demonstrated that major vault protein (MVP) induces type I IFN production during viral infection; however, little is known about the role of MVP in proinflammatory responses. In this study, we found in vitro that expression of MVP, IL-6, and IL-8 was inducible upon dsRNA stimulation or viral infection. Moreover, MVP was essential for the induction of IL-6 and IL-8, as impaired expression of IL-6 and IL-8 in MVP-deficient human PBMCs, human lung epithelial cells (A549), and THP-1 monocytes, as well as in murine splenocytes, peritoneal macrophages, and PBMCs from MVP-knockout (MVP(-/-)) mice, was observed. Upon investigation of the underlying mechanisms, we demonstrated that MVP acted in synergy with AP-1 (c-Fos) and CCAAT/enhancer binding protein (C/EBP)β-liver-enriched transcriptional activating protein to activate the IL6 and IL8 promoters. Introduction of mutations into the AP-1 and C/EBPβ binding sites on the IL6 and IL8 promoters resulted in the loss of synergistic activation with MVP. Furthermore, we found that MVP interacted with both c-Fos and C/EBPβ. The interactions promoted nuclear translocation and recruitment of these transcription factors to IL6 and IL8 promoter regions. In the MVP(-/-) mouse model, significantly decreased expression of early antiviral cytokines resulted in higher viral titer in the lung, higher mortality, and heavier lung damage after infection with lethal influenza A virus. Taken together, our findings help to delineate a novel role of MVP in host proinflammatory response. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. Molecular Characterization of Methicillin Resistant Staphylococcus aureus Strains Isolated from Intensive Care Units in Iran: ST22-SCCmec IV/t790 Emerges as the Major Clone.

    Science.gov (United States)

    Goudarzi, Mehdi; Goudarzi, Hossein; Sá Figueiredo, Agnes Marie; Udo, Edet E; Fazeli, Maryam; Asadzadeh, Mohammad; Seyedjavadi, Sima Sadat

    2016-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

  17. A metastatic colon adenocarcinoma harboring BRAF V600E has a durable major response to dabrafenib/trametinib and chemotherapy

    Directory of Open Access Journals (Sweden)

    Williams CB

    2015-12-01

    Full Text Available Casey B Williams,1,* Caitlin McMahon,2,* Siraj M Ali,2 Mark Abramovitz,1 Kirstin A Williams,1 Jessica Klein,1 Heidi McKean,1 Roman Yelensky,2 Thomas J George Jr,3 Julia A Elvin,2 Salil Soman,4 Doron Lipson,2 Juliann Chmielecki,2 Deborah Morosini,2 Vincent A Miller,2 Philip J Stephens,2 Jeffrey S Ross,2,5 Brian Leyland-Jones1 1Avera Cancer Institute, Sioux Falls, SD, USA; 2Foundation Medicine, Inc., Cambridge, MA, USA; 3University of Florida College of Medicine, Gainesville, FL, USA; 4Beth Israel Deaconess Medical Center, Boston, MA, USA; 5Albany Medical College, Albany, NY, USA *These authors contributed equally to this work Abstract: The subset of metastatic colorectal adenocarcinomas that harbor BRAF V600E mutations are aggressive tumors with significantly shortened survival and limited treatment options. Here we present a colorectal cancer patient whose disease progressed through standard chemotherapy and who developed liver metastasis. Comprehensive genomic profiling (FoundationOne® identified a BRAF V600E mutation in the liver lesion, as well as other genomic alterations consistent with colorectal cancers. Combination therapy of dabrafenib and trametinib with standard cytotoxic chemotherapy resulted in a durable major ongoing response for the patient. This report illustrates the utility of comprehensive genomic profiling with personalized targeted therapy for aggressive metastatic colorectal adenocarcinomas. Keywords: oxaliplatin, colorectal adenocarcinoma, combination targeted therapy, BRAF mutations

  18. Beta-lipotropin is the major component of the plasma opioid response to surgical stress in humans

    Energy Technology Data Exchange (ETDEWEB)

    Porro, C.A.; Facchinetti, F.; Bertellini, E.; Petraglia, F.; Stacca, R.; Barbieri, G.C.; Genazzani, A.R.

    1987-12-07

    There is growing experimental evidence that beta-endorphin immunoreactivity is raised by surgical stress in patients undergoing general anesthesia. As the assay methods employed to date did not allow to fully discriminate between beta-endorphin and its immediate precursor, beta-lipotropin, the authors have investigated in the present study plasma levels of these two peptides by separating them by chromatography on plasma extracts prior to radioimmunoassay. Beta-lipotropin, but not beta-endorphin, plasma levels were found to be significantly elevated during surgery in the general anesthesia group, while no change was found in either peptide concentration in the spinal one. Cortisol plasma levels also increased significantly 90 minutes after the beginning of surgery. Although the sampling time they adopted may have prevented them from detecting an early peak of beta-endorphin during the first 30 minutes of surgery, the major component of the pituitary opioid response to surgical stress appears to be related to beta-lipotropin. This is in agreement with results of experimental work on various kinds of stress in animals and humans and seems to rule out a role for plasma beta-endorphin in post-operative analgesia. 38 references, 1 figure, 1 table.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Time-course profiling of molecular stress responses to silver nanoparticles in the earthworm Eisenia fetida

    DEFF Research Database (Denmark)

    Hayashi, Yuya; Heckmann, Lars-Henrik; Simonsen, Vibeke

    2013-01-01

    ) with reference to dissolved silver salt (AgNO3). Principal component analysis of selected gene and enzyme response profiles revealed dissimilar patterns between AgNO3 and AgNP treatments and also over time. Despite the observed difference in molecular profiles, the body burdens of total Ag were within the same...... range (10–40 mg/kg dry weight worm) for both treatments with apparent correlation to the induction pattern of metallothionein. AgNO3 induced the genes and enzymes related to oxidative stress at day 1, after which markers of energy metabolism were all suppressed at day 2. Exposure to AgNPs likewise led...... to induction of oxidative stress genes at day 2, but with a temporal pattern shift to immune genes at day 14 following metabolic upregulation at day 7. The involvement of oxidative stress and subsequent alterations in immune gene regulation were as predicted by our in vitro study reported previously...

  4. A Hybrid Density Functional Theory/Molecular Mechanics Approach for Linear Response Properties in Heterogeneous Environments.

    Science.gov (United States)

    Rinkevicius, Zilvinas; Li, Xin; Sandberg, Jaime A R; Mikkelsen, Kurt V; Ågren, Hans

    2014-03-11

    We introduce a density functional theory/molecular mechanical approach for computation of linear response properties of molecules in heterogeneous environments, such as metal surfaces or nanoparticles embedded in solvents. The heterogeneous embedding environment, consisting from metallic and nonmetallic parts, is described by combined force fields, where conventional force fields are used for the nonmetallic part and capacitance-polarization-based force fields are used for the metallic part. The presented approach enables studies of properties and spectra of systems embedded in or placed at arbitrary shaped metallic surfaces, clusters, or nanoparticles. The capability and performance of the proposed approach is illustrated by sample calculations of optical absorption spectra of thymidine absorbed on gold surfaces in an aqueous environment, where we study how different organizations of the gold surface and how the combined, nonadditive effect of the two environments is reflected in the optical absorption spectrum.

  5. 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.

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Response of germinating barley seeds to Fusarium graminearum: The first molecular insight into Fusarium seedling blight

    DEFF Research Database (Denmark)

    Yang, Fen; Svensson, Birte; Finnie, Christine

    2011-01-01

    involved in primary metabolism and detoxification whereas the majority of down-regulated proteins were plant protease inhibitors. The results suggest that there is a link between increased energy metabolism and oxidative stress in the germinating barley seeds in response to F. graminearum infection, which......Fusarium seedling blight in cereals can result in significant reductions in plant establishment but has not received much attention. The disease often starts during seed germination due to sowing of the seeds infected by Fusarium spp. including Fusarium graminearum. In order to gain the first...

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  16. A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.

    Science.gov (United States)

    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.

  17. Molecular genetics of Turner syndrome: correlation with clinical phenotype and response to growth hormone therapy.

    Science.gov (United States)

    Tsezou, A; Hadjiathanasiou, C; Gourgiotis, D; Galla, A; Kavazarakis, E; Pasparaki, A; Kapsetaki, M; Sismani, C; Theodoridis, C; Patsalis, P C; Moschonas, N; Kitsiou, S

    1999-12-01

    To correlate the origin of the retained X in Turner syndrome with phenotype, pre-treatment height and response to recombinant human growth hormone (rhGH) therapy, systematic clinical assessment and molecular studies were carried out in 33 Greek children with Turner syndrome and their parents including 18 children with 45,X and 15 with X-mosaicism. Microsatellite markers on X chromosomes (DXS101 and DXS337) revealed that the intact X was paternal (Xp) in 15/30 and maternal (Xm) in 15/30 children, while 3/33 families were non-informative. No significant relationship was found between parental origin of the retained X and birth weight/length/gestational age, blepharoptosis, pterygium colli, webbed neck, low hairline, abnormal ears, lymphoedema, short 4th metacarpal, shield chest, widely spaced nipples, cubitus valgus, pigmented naevi, streak gonads, and cardiovascular/renal anomalies. With regard to the children's pre-treatment height, there was a significant correlation with maternal height and target height in both Xm and Xp groups. No differences were found between Xm and Xp groups and the improvement of growth velocity (GV) during the first and second year of rhGH administration, while for both groups GV significantly improved with rhGH by the end of the first and the second year. To our knowledge, this is the first attempt to correlate the parental origin of Turner syndrome with the response to rhGH therapy.

  18. Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

    Science.gov (United States)

    Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

    2016-11-25

    Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.

  19. Characterization of majority and minority carrier deep levels in p-type GaN:Mg grown by molecular beam epitaxy using deep level optical spectroscopy

    International Nuclear Information System (INIS)

    Armstrong, A.; Caudill, J.; Ringel, S. A.; Corrion, A.; Poblenz, C.; Mishra, U. K.; Speck, J. S.

    2008-01-01

    Deep level defects in p-type GaN:Mg grown by molecular beam epitaxy were characterized using steady-state photocapacitance and deep level optical spectroscopy (DLOS). Low frequency capacitance measurements were used to alleviate dispersion effects stemming from the deep Mg acceptor. Use of DLOS enabled a quantitative survey of both deep acceptor and deep donor levels, the latter being particularly important due to the limited understanding of minority carrier states for p-type GaN. Simultaneous electron and hole photoemissions resulted in a convoluted deep level spectrum that was decoupled by emphasizing either majority or minority carrier optical emission through control of the thermal filling time conditions. In this manner, DLOS was able to resolve and quantify the properties of deep levels residing near both the conduction and valence bandedges in the same sample. Bandgap states through hole photoemission were observed at E v +3.05 eV, E v +3.22 eV and E v +3.26 eV. Additionally, DLOS revealed levels at E c -3.24 eV and E c -2.97 eV through electron emission to the conduction band with the former attributed to the Mg acceptor itself. The detected deep donor concentration is less than 2% of activated [Mg] and demonstrates the excellent quality of the film

  20. Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions

    Directory of Open Access Journals (Sweden)

    Carmine Tomasetti

    2017-01-01

    Full Text Available Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of “synapse-based” psychiatric therapeutic strategies.

  1. 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.

  2. 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.

    Science.gov (United States)

    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.

  3. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2018-01-01

    Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Marsh plant response to metals: Exudation of aliphatic low molecular weight organic acids (ALMWOAs)

    Science.gov (United States)

    Rocha, A. Cristina S.; Almeida, C. Marisa R.; Basto, M. Clara P.; Vasconcelos, M. Teresa S. D.

    2016-03-01

    Metal exposure is known to induce the production and secretion of substances, such as aliphatic low molecular weight organic acids (ALMWOAs), into the rhizosphere by plant roots. Knowledge on this matter is extensive for soil plants but still considerably scarce regarding marsh plants roots adapted to high salinity media. Phragmites australis and Halimione portulacoides, two marsh plants commonly distributed in European estuarine salt marshes, were used to assess the response of roots of both species, in terms of ALMWOAs exudation, to Cu, Ni and Cd exposure (isolated and in mixture since in natural environment, they are exposed to mixture of metals). As previous studies were carried out in unrealistic and synthetic media, here a more natural medium was selected. Therefore, in vitro experiments were carried out, with specimens of both marsh plants, and in freshwater contaminated with two different Cu, Ni and Cd concentrations (individual metal and in mixture). Both marsh plants were capable of liberating ALMWOAs into the surrounding medium. Oxalic, citric and maleic acids were found in P. australis root exudate solutions and oxalic and maleic acids in H. portulacoides root exudate solutions. ALMWOA liberation by both plants was plant species and metal-dependent. For instance, Cu affected the exudation of oxalic acid by H. portulacoides and of oxalic and citric acids by P. australis roots. In contrast, Ni and Cd did not stimulate any specific response. Regarding the combination of all metals, H. portulacoides showed a similar response to that observed for Cu individually. However, in the P. australis case, at high metal concentration mixture, a synergetic effect led to the increase of oxalic acid levels in root exudate solution and to a decrease of citric acid liberation. A correlation between ALMWOAs exudation and metal accumulation could not be established. P. australis and H. portulacoides are considered suitable metal phytoremediators of estuarine impacted areas

  7. 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

  8. 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

  9. 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

  10. Influence of the Compositional Grading on Concentration of Majority Charge Carriers in Near-Surface Layers of n(p)-HgCdTe Grown by Molecular Beam Epitaxy

    Science.gov (United States)

    Voitsekhovskii, A. V.; Nesmelov, S. N.; Dzyadukh, S. M.

    2018-02-01

    The capacitive characteristics of metal-insulator-semiconductor (MIS) structures based on the compositionally graded Hg1-xCdxTe created by molecular beam epitaxy have been experimentally investigated in a wide temperature range (8-77 K). A program has been developed for numerical simulation of ideal capacitance-voltage (C-V) characteristics in the low-frequency and high-frequency approximations. The concentrations of the majority carriers in the near-surface semiconductor layer are determined from the values of the capacitances in the minima of low-frequency C-V curves. For MIS structures based on p-Hg1-xCdxTe, the effect of the presence of the compositionally graded layer on the hole concentration in the near-surface semiconductor layer, determined from capacitive measurements, has not been established. Perhaps this is due to the fact that the concentration of holes in the near-surface layer largely depends on the type of dielectric coating and the regimes of its application. For MIS structures based on n-Hg1-x Cd x Te (x = 0.22-0.23) without a graded-gap layer, the electron concentration determined by the proposed method is close to the average concentration determined by the Hall measurements. The electron concentration in the near-surface semiconductor layer of the compositionally graded n-Hg1-x Cd x Te (x = 0.22-0.23) found from the minimum capacitance value is much higher than the average electron concentration determined by the Hall measurements. The results are qualitatively explained by the creation of additional intrinsic donor-type defects in the near-surface compositionally graded layer of n-Hg1-x Cd x Te.

  11. Molecular pathways in the bystander response of cells exposed to very low fluences of alpha particles

    International Nuclear Information System (INIS)

    Little, J.B.

    2000-01-01

    Full text: We have examined biological effects in cell populations exposed to very low mean doses of alpha radiation by which only a small fraction of the cells are actually traversed by an alpha particle. We showed earlier that an enhanced frequency of sister chromatid exchanges and HPRT mutations occur in the non-irradiated, 'bystander' cells. The frequency of mutations induced by a single alpha particle traversing the nucleus of a cell was increased nearly fivefold at the lowest fluence studied, a result of mutations occurring in bystander cells. This was associated with a similar increase in the induction of micronuclei, indicating the induction of DNA damage in bystander cells. In order to gain information concerning molecular pathways, we studied changes in gene expression in bystander cells in confluent cultures of human diploid fibroblasts or mouse embryo-derived fibroblasts (MEFs) by western analysis and in-situ immunofluorescence. The expression levels of p53, p21 Waf1 and p34 cdc2 were significantly modulated in bystander cells. The upregulation of p53 and p21 Waf1 did not occur in cultures irradiated at low density, and was markedly reduced in the presence of the gap junction inhibitor lindane. The importance of gap-junction mediated intercellular communication was confirmed in connexin-43 knockout MEFs. Western blot analyses and electrophoretic mobility shift assays indicate that the bystander response is suppressed by incubation with superoxide dismutase as well as an inhibitor of NADPH oxidase, and is associated with the induction of NFKB, suggesting the effect is mediated by oxidative stress. The stress-activated protein kinase p38 and its downstream effector ATF2 are also induced in bystander cells independent of oxidative stress. These results will be discussed in terms of whether activation of the p53 damage response pathway is the direct result of signaling from irradiated cells, or rather is a consequence of DNA induced damage in the bystander

  12. 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

  13. 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.

    Science.gov (United States)

    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

  14. 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.

  15. Molecular Typing of Staphylococcus Aureus Isolate Responsible for Staphylococcal Poisoning Incident in Homemade Food.

    Science.gov (United States)

    Macori, Guerrino; Bellio, Alberto; Bianchi, Daniela Manila; Gallina, Silvia; Adriano, Daniela; Zuccon, Fabio; Chiesa, Francesco; Acutis, Pier Luigi; Casalinuovo, Francesco; Decastelli, Lucia

    2016-04-19

    In October 2012, two persons fell ill with symptoms consistent with staphylococcal food poisoning after eating home-canned tuna fish and tomatoes. Laboratory investigation detected the enterotoxins in the home-canned tuna and molecular analysis of the isolated Staphylococcus aureus confirmed it carried toxin genes. Qualitative enzyme-linked immunosorbent assay and enzime linked fluorescent assay methods and quantitative assay identified the enterotoxins in the food leftovers, specifically staphylococcal enterotoxins type A (SEA) and D (SED), respectively 0.49 and 2.04 ng/g. The laboratory results are discussed considering the relation to the fish in oil, survival and heat resistance of S. aureus , and presumptive microbial contamination due to improper handling during home-canning procedures. This is the first reported cluster of foodborne illnesses due to staphylococcal enterotoxins in tuna in Italy. In this study, we reported cases described and analysed for their spa -type. Showing a high heterogeneity of isolates, spa -type t 13252 is correlated in a node of the minimum spanning tree and it has never been reported as responsible for foodborne outbreak. This case underlines the importance of risk communication and dissemination of home-canning guidelines to reduce the incidence of foodborne outbreaks caused by homemade conserves.

  16. Molecular typing of Staphylococcus aureus isolate responsible for staphylococcal poisoning incident in homemade food

    Directory of Open Access Journals (Sweden)

    Guerrino Macori

    2016-06-01

    Full Text Available In October 2012, two persons fell ill with symptoms consistent with staphylococcal food poisoning after eating home-canned tuna fish and tomatoes. Laboratory investigation detected the enterotoxins in the home-canned tuna and molecular analysis of the isolated Staphylococcus aureus confirmed it carried toxin genes. Qualitative enzyme-linked immunosorbent assay and enzime linked fluorescent assay methods and quantitative assay identified the enterotoxins in the food leftovers, specifically staphylococcal enterotoxins type A (SEA and D (SED, respectively 0.49 and 2.04 ng/g. The laboratory results are discussed considering the relation to the fish in oil, survival and heat resistance of S. aureus, and presumptive microbial contamination due to improper handling during home-canning procedures. This is the first reported cluster of foodborne illnesses due to staphylococcal enterotoxins in tuna in Italy. In this study, we reported cases described and analysed for their spa-type. Showing a high heterogeneity of isolates, spa-type t13252 is correlated in a node of the minimum spanning tree and it has never been reported as responsible for foodborne outbreak. This case underlines the importance of risk communication and dissemination of home-canning guidelines to reduce the incidence of foodborne outbreaks caused by homemade conserves.

  17. Temperature control of molecular circuit switch responsible for virulent phenotype expression in uropathogenic Escherichia coli

    Science.gov (United States)

    Samoilov, Michael

    2010-03-01

    The behavior and fate of biological organisms are to a large extent dictated by their environment, which can be often viewed as a collection of features and constraints governed by physics laws. Since biological systems comprise networks of molecular interactions, one such key physical property is temperature, whose variations directly affect the rates of biochemical reactions involved. For instance, temperature is known to control many gene regulatory circuits responsible for pathogenicity in bacteria. One such example is type 1 fimbriae (T1F) -- the foremost virulence factor in uropathogenic E. coli (UPEC), which accounts for 80-90% of all community-acquired urinary tract infections (UTIs). The expression of T1F is randomly `phase variable', i.e. individual cells switch between virulent/fimbriate and avirulent/afimbriate phenotypes, with rates regulated by temperature. Our computational investigation of this process, which is based on FimB/FimE recombinase-mediated inversion of fimS DNA element, offers new insights into its discrete-stochastic kinetics. In particular, it elucidates the logic of T1F control optimization to the host temperature and contributes further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs.

  18. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel.

    Science.gov (United States)

    Kharaziha, Pedram; Chioureas, Dimitris; Rutishauser, Dorothea; Baltatzis, George; Lennartsson, Lena; Fonseca, Pedro; Azimi, Alireza; Hultenby, Kjell; Zubarev, Roman; Ullén, Anders; Yachnin, Jeffrey; Nilsson, Sten; Panaretakis, Theocharis

    2015-08-28

    Docetaxel is a cornerstone treatment for metastatic, castration resistant prostate cancer (CRPC) which remains a leading cause of cancer-related deaths, worldwide. The clinical usage of docetaxel has resulted in modest gains in survival, primarily due to the development of resistance. There are currently no clinical biomarkers available that predict whether a CRPC patient will respond or acquire resistance to this therapy. Comparative proteomics analysis of exosomes secreted from DU145 prostate cancer cells that are sensitive (DU145 Tax-Sen) or have acquired resistance (DU145 Tax-Res) to docetaxel, demonstrated significant differences in the amount of exosomes secreted and in their molecular composition. A panel of proteins was identified by proteomics to be differentially enriched in DU145 Tax-Res compared to DU145 Tax-Sen exosomes and was validated by western blotting. Importantly, we identified MDR-1, MDR-3, Endophilin-A2 and PABP4 that were enriched only in DU145 Tax-Res exosomes. We validated the presence of these proteins in the serum of a small cohort of patients. DU145 cells that have uptaken DU145 Tax-Res exosomes show properties of increased matrix degradation. In summary, exosomes derived from DU145 Tax-Res cells may be a valuable source of biomarkers for response to therapy.

  19. Molecular hydrogen is involved in phytohormone signaling and stress responses in plants.

    Directory of Open Access Journals (Sweden)

    Jiqing Zeng

    Full Text Available Molecular hydrogen (H2 metabolism in bacteria and algae has been well studied from an industrial perspective because H2 is viewed as a potential future energy source. A number of clinical trials have recently reported that H2 is a therapeutic antioxidant and signaling molecule. Although H2 metabolism in higher plants was reported in some early studies, its biological effects remain unclear. In this report, the biological effects of H2 and its involvement in plant hormone signaling pathways and stress responses were determined. Antioxidant enzyme activity was found to be increased and the transcription of corresponding genes altered when the effects of H2 on the germination of mung bean seeds treated with phytohormones was investigated. In addition, upregulation of several phytohormone receptor genes and genes that encode a few key factors involved in plant signaling pathways was detected in rice seedlings treated with HW. The transcription of putative rice hydrogenase genes, hydrogenase activity, and endogenous H2 production were also determined. H2 production was found to be induced by abscisic acid, ethylene, and jasmonate acid, salt, and drought stress and was consistent with hydrogenase activity and the expression of putative hydrogenase genes in rice seedlings. Together, these results suggest that H2 may have an effect on rice stress tolerance by modulating the output of hormone signaling pathways.

  20. 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

  1. Molecular genetics of human immune responsiveness to Lolium perenne (rye) allergen, Lol p III.

    Science.gov (United States)

    Ansari, A A; Freidhoff, L R; Marsh, D G

    1989-01-01

    Lol p II and III are each about 11-kD protein allergens from the pollen of Lolium perenne (rye grass). We have found that human immune responses (IgE and IgG antibodies) to both proteins are significantly associated with HLA-DR3. In addition, the two proteins are cross-reactive with the antibodies in many human sera (about 84% human sera showed the cross-reactivity). We have determined greater than 90% of the amino acid sequences of the two proteins and found that they are at least 54% homologous. Berzofsky found that 75% of the 23 known T cell sites in various proteins had an amphipathic structure. Our analysis by the same method showed that both Lol p II and III have a major region of amphipathicity (at residues 61-67, Lol p III numbering) which might contain sites for binding to an Ia molecule and a T cell receptor. This region is identical between Lol p II and III, except for an Arg-Lys substitution, and could account, in part, for the DR3 association with responsiveness to both molecules. An interesting difference between the two proteins is that immune response to Lol p III is associated with DR5 (in addition to DR3), whereas no DR5 association is found in the case of Lol p II. One possibility is that Lol p III has an additional site which binds to the DR5 Ia molecule. Lol p III indeed has a second highly amphiphathic peptide, 24-30 (Lol p III 24 R P G D T L A 30), which is different and not amphipathic in Lol p II.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Cardiac molecular-acclimation mechanisms in response to swimming-induced exercise in Atlantic salmon.

    Directory of Open Access Journals (Sweden)

    Vicente Castro

    Full Text Available Cardiac muscle is a principal target organ for exercise-induced acclimation mechanisms in fish and mammals, given that sustained aerobic exercise training improves cardiac output. Yet, the molecular mechanisms underlying such cardiac acclimation have been scarcely investigated in teleosts. Consequently, we studied mechanisms related to cardiac growth, contractility, vascularization, energy metabolism and myokine production in Atlantic salmon pre-smolts resulting from 10 weeks exercise-training at three different swimming intensities: 0.32 (control, 0.65 (medium intensity and 1.31 (high intensity body lengths s(-1. Cardiac responses were characterized using growth, immunofluorescence and qPCR analysis of a large number of target genes encoding proteins with significant and well-characterized function. The overall stimulatory effect of exercise on cardiac muscle was dependent on training intensity, with changes elicited by high intensity training being of greater magnitude than either medium intensity or control. Higher protein levels of PCNA were indicative of cardiac growth being driven by cardiomyocyte hyperplasia, while elevated cardiac mRNA levels of MEF2C, GATA4 and ACTA1 suggested cardiomyocyte hypertrophy. In addition, up-regulation of EC coupling-related genes suggested that exercised hearts may have improved contractile function, while higher mRNA levels of EPO and VEGF were suggestive of a more efficient oxygen supply network. Furthermore, higher mRNA levels of PPARα, PGC1α and CPT1 all suggested a higher capacity for lipid oxidation, which along with a significant enlargement of mitochondrial size in cardiac myocytes of the compact layer of fish exercised at high intensity, suggested an enhanced energetic support system. Training also elevated transcription of a set of myokines and other gene products related to the inflammatory process, such as TNFα, NFκB, COX2, IL1RA and TNF decoy receptor. This study provides the first

  3. DOD Major Automated Information Systems: Improvements Can Be Made in Reporting Critical Changes and Clarifying Leadership Responsibility

    Science.gov (United States)

    2016-03-01

    Leadership Responsibility Report to Congressional Committees March 2016 GAO-16-336 United States Government Accountability Office United...INFORMATION SYSTEMS Improvements Can Be Made in Reporting Critical Changes and Clarifying Leadership Responsibility Why GAO Did This Study The National...milestone decisions for MAIS programs. AT&L can delegate decision authority for MAIS programs to a component head who may further delegate the authority

  4. Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

    Science.gov (United States)

    Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

    2014-05-01

    Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. 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

  6. Characterization of the local and systemic immune responses in patients with cutaneous leishmaniasis due to Leishmania major

    DEFF Research Database (Denmark)

    Gaafar, A; Veress, B; Permin, H

    1999-01-01

    In this study skin biopsies and peripheral blood samples were obtained from patients with cutaneous leishmaniasis caused by Leishmania major. Samples were obtained at diagnosis and during healing when the lesions had regressed to half the original size. At diagnosis most of the cells expressed HLA...

  7. No effect of melatonin to modify surgical-stress response after major vascular surgery: a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Kücükakin, B; Wilhelmsen, M; Lykkesfeldt, Jens

    2010-01-01

    A possible mechanism underlying cardiovascular morbidity after major vascular surgery may be the perioperative ischaemia-reperfusion with excessive oxygen-derived free-radical production and increased levels of circulating inflammatory mediators. We examined the effect of melatonin infusion during...... surgery and oral melatonin treatment for 3 days after surgery on biochemical markers of oxidative and inflammatory stress....

  8. The response of Plantago major ssp pleiosperma to elevated CO2 is modulated by the formation of secondary shoots

    NARCIS (Netherlands)

    Coelho Guerra da Fonseca, F.M; den Hertog, J; Stulen, G

    The effect of elevated CO2 on the relative growth rate (RGR) of Plantago major ssp. pleiosperma was studied during the vegetative stage, in relation to plant development, by growing plants at 350 mu l l(-1) or at 700 mu l l(-1) CO2 in non-limiting nutrient solution with nitrate. To minimize

  9. Prevalence of MTHFR C677T and MS A2756G polymorphisms in major depressive disorder, and their impact on response to fluoxetine treatment

    Science.gov (United States)

    To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response. We screened 224 subjects (52% female, mean age 39 +/- 11 years) with SCID-diagnosed major...

  10. 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,…

  11. Differential responsiveness of Holstein and Angus dermal fibroblasts to LPS challenge occurs without major differences in the methylome.

    Science.gov (United States)

    Benjamin, Aimee L; Green, Benjamin B; Crooker, Brian A; McKay, Stephanie D; Kerr, David E

    2016-03-24

    We have previously found substantial animal-to-animal and age-dependent variation in the response of Holstein fibroblast cultures challenged with LPS. To expand on this finding, fibroblast cultures were established from dairy (Holstein) and beef (Angus) cattle and challenged with LPS to examine breed-dependent differences in the innate immune response. Global gene expression was measured by RNA-Seq, while an epigenetic basis for expression differences was examined by methylated CpG island recovery assay sequencing (MIRA-Seq) analysis. The Holstein breed displayed a more robust response to LPS than the Angus breed based on RNA-Seq analysis of cultures challenged with LPS for 0, 2, and 8 h. Several immune-associated genes were expressed at greater levels (FDR Angus fibroblasts, and two of these regions fell within the promoter region (-2500 to +500 bp of the transcription start site) of the genes NTRK2 and ADAMTS5. Fibroblasts isolated from Holstein cattle display a more robust response to LPS in comparison to cultures from Angus cattle. Different selection strategies and management practices exist between these two breeds that likely give rise to genetic and epigenetic factors contributing to the different immune response phenotypes.

  12. 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.

  13. Differential immune microenvironments and response to immune checkpoint blockade amongst molecular subtypes of murine medulloblastoma

    Science.gov (United States)

    Pham, Christina D.; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M.; Yearley, Jennifer H.; Sayour, Elias J.; Pei, Yanxin; Moore, Colin; McLendon, Roger E.; Huang, Jianping; Sampson, John H.; Wechsler-Reya, Robert; Mitchell, Duane A.

    2016-01-01

    PURPOSE Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma (MB), the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and Group 3 MB for preclinical evaluation in immunocompetent C57BL/6 mice. METHODS AND RESULTS Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid derived suppressor cells and tumor-associated macrophages in murine SHH model tumors compared with Group 3 tumors. However, murine Group 3 tumors had higher percentages of CD8+ PD-1+ T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial Group 3 tumors compared to SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1+ peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3+ T cells within the tumor microenvironment. CONCLUSIONS This is the first immunologic characterization of preclinical models of molecular subtypes of MB and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. PMID:26405194

  14. Molecular characteristics of hemoglobins in blood clam and their immune responses to bacterial infection.

    Science.gov (United States)

    Xu, Bin; Zhang, Yanan; Jing, Zhao; Fan, Tingjun

    2017-06-01

    Bivalve hemoglobins have antibacterial activities, while the underlying mechanisms remain poorly understood. In our study, three full-length cDNAs of hemoglobins from blood clam skHbs were obtained, encoding putative polypeptides of 147, 150, and 152 amino acids, respectively. Predicted advanced protein structures showed that the skHbs had amphipathic antibacterial structures, displayed the typical structural characteristics of proteins with globin-like fold containing numerous alpha-helixes, and forming a homodimeric skHbI and a heterotetrameric skHbII complex. After injected with alive and heat-killed Gram-positive bacteria Bacillus subtilis, the mRNA levels of skHbI and skHbII were both significantly upregulated through increasing the expression of peptidoglycan recognition protein-like (PGRP-like) protein and Toll-like receptor (TLR-like) protein induced by peptidoglycan on the surface of the bacteria, but there were no obvious differences in their protein levels. Besides, reactive oxygen species (ROS) was detected to participate in the resistance to B. subtilis. These implied that skHbs could involve in the innate immune responses to Gram-positive bacterial infection directly with their amphipathic structures and indirectly by increasing ROS production through PGRP triggering Toll pathway. In conclusion, our findings reveal the structural characteristics of skHbs and their mechanism against Gram-positive bacteria thereby providing the molecular evidence for fundamental innate antibacterial activities by invoking respiratory proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

    Science.gov (United States)

    Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

    2009-06-09

    Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

  16. Differential Immune Microenvironments and Response to Immune Checkpoint Blockade among Molecular Subtypes of Murine Medulloblastoma.

    Science.gov (United States)

    Pham, Christina D; Flores, Catherine; Yang, Changlin; Pinheiro, Elaine M; Yearley, Jennifer H; Sayour, Elias J; Pei, Yanxin; Moore, Colin; McLendon, Roger E; Huang, Jianping; Sampson, John H; Wechsler-Reya, Robert; Mitchell, Duane A

    2016-02-01

    Despite significant strides in the identification and characterization of potential therapeutic targets for medulloblastoma, the role of the immune system and its interplay with the tumor microenvironment within these tumors are poorly understood. To address this, we adapted two syngeneic animal models of human Sonic Hedgehog (SHH)-driven and group 3 medulloblastoma for preclinical evaluation in immunocompetent C57BL/6 mice. Multicolor flow cytometric analyses were used to phenotype and characterize immune infiltrating cells within established cerebellar tumors. We observed significantly higher percentages of dendritic cells, infiltrating lymphocytes, myeloid-derived suppressor cells, and tumor-associated macrophages in murine SHH model tumors compared with group 3 tumors. However, murine group 3 tumors had higher percentages of CD8(+) PD-1(+) T cells within the CD3 population. PD-1 blockade conferred superior antitumor efficacy in animals bearing intracranial group 3 tumors compared with SHH group tumors, indicating that immunologic differences within the tumor microenvironment can be leveraged as potential targets to mediate antitumor efficacy. Further analysis of anti-PD-1 monoclonal antibody localization revealed binding to PD-1(+) peripheral T cells, but not tumor infiltrating lymphocytes within the brain tumor microenvironment. Peripheral PD-1 blockade additionally resulted in a marked increase in CD3(+) T cells within the tumor microenvironment. This is the first immunologic characterization of preclinical models of molecular subtypes of medulloblastoma and demonstration that response to immune checkpoint blockade differs across subtype classification. Our findings also suggest that effective anti-PD-1 blockade does not require that systemically administered antibodies penetrate the brain tumor microenvironment. ©2015 American Association for Cancer Research.

  17. 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.

  18. 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...

  19. Surrogate markers of visceral fat and response to anti-depressive treatment in patients with major depressive disorder

    DEFF Research Database (Denmark)

    Tønning, Morten; Petersen, Dorthe; Steglich-Petersen, Marie

    2017-01-01

    Background: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship. Aims: The aim of this study was to pr......Background: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship. Aims: The aim of this study...... was to prospectively investigate whether visceral fat, as measured by hip-to-waist ratio and waist circumference, affects treatment outcome in patients with major depressive disorder in patients attending a hospital psychiatric care unit in Denmark. Methods: The study was conducted as an observational prospective......) interviews and HAM-D6 self-rating questionnaires. Results: No differences were found in outcome between groups of patients with high vs low visceral fat in this population. Conclusions: The lack of association was evident for all surrogate markers of visceral fat, and suggests that visceral fat has no impact...

  20. Responsiveness of the major birch allergen Bet v 1 scaffold to the gastric environment: Impact on structure and allergenic activity

    DEFF Research Database (Denmark)

    Sancho, Ana I; Wangorsch, Andrea; Jensen, Bettina M

    2011-01-01

    Four Bet v 1 homologous food allergens from celeriac (rApi g 1), apple (rMal d 1), peach (rPru p 1) and hazelnut (rCor a 1), were used to probe the structural responsiveness of the Bet v 1 scaffold to gastric digestion conditions and its impact on allergenicity....

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

    Science.gov (United States)

    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.

  2. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.

    Science.gov (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D

    2017-01-05

    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  3. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

    Directory of Open Access Journals (Sweden)

    Ang Cui

    Full Text Available Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction. This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Stress responsive miR-31 is a major modulator of mouse intestinal stem cells during regeneration and tumorigenesis.

    Science.gov (United States)

    Tian, Yuhua; Ma, Xianghui; Lv, Cong; Sheng, Xiaole; Li, Xiang; Zhao, Ran; Song, Yongli; Andl, Thomas; Plikus, Maksim V; Sun, Jinyue; Ren, Fazheng; Shuai, Jianwei; Lengner, Christopher J; Cui, Wei; Yu, Zhengquan

    2017-09-05

    Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis. Mechanistically, miR-31 acts to balance input from Wnt, BMP, TGFβ signals to coordinate control of intestinal homeostasis, regeneration and tumorigenesis. We further find that miR-31 is regulated by the STAT3 signaling pathway in response to radiation injury. These findings identify miR-31 as a critical modulator of ISC biology, and a potential therapeutic target for a broad range of intestinal regenerative disorders and cancers.

  7. A meta-analysis of responses of canopy photosynthetic conversion efficiency to environmental factors reveals major causes of yield gap

    Science.gov (United States)

    Slattery, Rebecca A.; Ainsworth, Elizabeth A.; Ort, Donald R.

    2013-01-01

    Improving plant energy conversion efficiency (εc) is crucial for increasing food and bioenergy crop production and yields. Using a meta-analysis, the effects of greenhouse gases, weather-related stresses projected to intensify due to climate change, and management practices including inputs, shading, and intercropping on εc were statistically quantified from 140 published studies to identify where improvements would have the largest impact on closing yield gaps. Variation in the response of εc to treatment type and dosage, plant characteristics, and growth conditions were also examined. Significant mean increases in εc were caused by elevated [CO2] (20%), shade (18%), and intercropping (15%). εc increased curvilinearly up to 55% with nitrogen additions whereas phosphorus application was most beneficial at low levels. Significant decreases in εc of –8.4% due to elevated [O3], –16.8% due to water stress, and –6.5% due to foliar damage were found. A non-significant decrease in εc of –17.3% was caused by temperature stress. These results identify the need to engineer greater stress tolerance and enhanced responses to positive factors such as [CO2] and nitrogen to improve average yields and yield potential. Optimizing management strategies will also enhance the benefits possible with intercropping, shade, and pest resilience. To determine optimal practices for εc improvement, further studies should be conducted in the field since several responses were exaggerated by non-field experimental conditions. PMID:23873996

  8. Photosynthetic and molecular responses of the marine diatom Thalassiosira pseudonana to triphenyltin exposure

    International Nuclear Information System (INIS)

    Yi, Andy Xianliang; Leung, Priscilla T.Y.; Leung, Kenneth M.Y.

    2014-01-01

    superoxide dismutase, which can function to maintain the capacity of PSII and stabilize the photosynthesis efficiency as reflected by the unchanged Φ Po and Φ 2 values at 0.5 μg/L TPTCl. In contrast, the excess toxicity that caused by TPTCl at the high concentration (1.0 μg/L TPTCl) might directly damage the proteins, inhibit their expression, and/or cause the suppression of metabolism as indicated by the down-regulation of most studied proteins and genes, which could ultimately inhibit the photosynthesis and growth of the algae. Overall, this study comprehensively elucidated the toxicity effects of TPT on T. pseudonana, and partially revealed the molecular toxic mechanisms and corresponding defence responses in this model algal species

  9. Photosynthetic and molecular responses of the marine diatom Thalassiosira pseudonana to triphenyltin exposure

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Andy Xianliang; Leung, Priscilla T.Y.; Leung, Kenneth M.Y., E-mail: kmyleung@hku.hk

    2014-09-15

    manganese superoxide dismutase, which can function to maintain the capacity of PSII and stabilize the photosynthesis efficiency as reflected by the unchanged Φ{sub Po} and Φ{sub 2} values at 0.5 μg/L TPTCl. In contrast, the excess toxicity that caused by TPTCl at the high concentration (1.0 μg/L TPTCl) might directly damage the proteins, inhibit their expression, and/or cause the suppression of metabolism as indicated by the down-regulation of most studied proteins and genes, which could ultimately inhibit the photosynthesis and growth of the algae. Overall, this study comprehensively elucidated the toxicity effects of TPT on T. pseudonana, and partially revealed the molecular toxic mechanisms and corresponding defence responses in this model algal species.

  10. Molecular Characterization of Barrier Properties in Follicle-Associated Epithelium of Porcine Peyer's Patches Reveals Major Sealing Function of Claudin-4

    Directory of Open Access Journals (Sweden)

    Judith Radloff

    2017-08-01

    Full Text Available The pig represents a preferred model for the analysis of intestinal immunology. However, the barrier of the follicle-associated epithelium (FAE covering porcine Peyer's patches (PP has not yet been characterized in detail. This study aimed to perform this characterization in order to pave the way toward an understanding of the functional contribution of epithelial barrier properties in gut immunology. Porcine tissue specimens were taken from the distal small intestine in order to obtain electrophysiological data of PP FAE and neighboring villous epithelium (VE, employing the Ussing chamber technique. Transepithelial resistance (TER and paracellular fluorescein flux were measured, and tissues were morphometrically compared. In selfsame tissues, expression and localization of major tight junction (TJ proteins (claudin-1, -2, -3, -4, -5, and -8 were analyzed. PP FAE specimens showed a higher TER and a lower apparent permeability for sodium fluorescein than VE. Immunoblotting revealed an expression of all claudins within both epithelia, with markedly stronger expression of the sealing TJ protein claudin-4 in PP FAE compared with the neighboring VE. Immunohistochemistry confirmed the expression and localization of all claudins in both PP FAE and VE, with stronger claudin-4 abundance in PP FAE. The results are in accordance with the physiological function of the FAE, which strongly regulates and limits antigen uptake determining a mandatory transcellular route for antigen presentation, highlighting the importance of this structure for the first steps of the intestinal immune response. Thus, this study provides detailed insights into the specific barrier properties of the porcine FAE covering intestinal PP, at the interface of intestinal immunology and barriology.

  11. 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...

  12. Solar sources of interplanetary southward B/sub z/ events responsible for major magnetic storms (1978--1979)

    International Nuclear Information System (INIS)

    Tang, F.; Tsurutani, B.T.; Gonzalez, W.D.; Akasofu, S.I.; Smith, E.J.

    1989-01-01

    Tsurutani et al. [1988] analyzed the 10 intense interplanetary southward B/sub z/ events that led to major magnetic storms (Dst 3.0) are associated with prominence eruptions. For three of the five southward B/sub z/ events in which the driver gases are the causes of the intense southward field leading to magnetic storms, the photospheric fields of the solar sources have no dominant southward component, indicating the driver gas fields do not always result from a simple outward convection of solar magnetic fields. Finally we compare the solar events and their resulting interplanetary shocks and find that the standard solar parameters do not correlate with the strengths of the resulting shocks at 1 AU. The implications are discussed. copyright American Geophysical Union 1989

  13. 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.

  14. 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.

  15. Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients.

    Science.gov (United States)

    Widenmeyer, Melanie; Griesemann, Heinrich; Stevanović, Stefan; Feyerabend, Susan; Klein, Reinhild; Attig, Sebastian; Hennenlotter, Jörg; Wernet, Dorothee; Kuprash, Dmitri V; Sazykin, Alexei Y; Pascolo, Steve; Stenzl, Arnulf; Gouttefangeas, Cécile; Rammensee, Hans-Georg

    2012-07-01

    CD4(+) T cells have been shown to be crucial for the induction and maintenance of cytotoxic T cell responses and to be also capable of mediating direct tumor rejection. Therefore, the anticancer therapeutic efficacy of peptide-based vaccines may be improved by addition of HLA class II epitopes to stimulate T helper cells. Survivin is an apoptosis inhibiting protein frequently overexpressed in tumors. Here we describe the first immunological evaluation of a survivin-derived CD4(+) T cell epitope in a multipeptide immunotherapy trial for prostate carcinoma patients. The survivin peptide is promiscuously presented by several human HLA-DRB1 molecules and, most importantly, is naturally processed by dendritic cells. In vaccinated patients, it was able to induce frequent, robust and multifunctional CD4(+) T cell responses, as monitored by IFN-γ ELISPOT and intracellular cytokine staining. Thus, this HLA-DR restricted epitope is broadly immunogenic and should be valuable for stimulating T helper cells in patients suffering from a wide range of tumors. Copyright © 2011 UICC.

  16. Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation

    Directory of Open Access Journals (Sweden)

    Manuel J. Muñoz

    2017-03-01

    Full Text Available We have previously found that UV irradiation promotes RNA polymerase II (RNAPII hyperphosphorylation and subsequent changes in alternative splicing (AS. We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER, and reduced by the absence of XPE, the main NER sensor of PDs. The mechanism involves activation of the protein kinase ATR that mediates the UV-induced RNAPII hyperphosphorylation. Our results define the sequence UV-PDs-NER-ATR-RNAPII-AS as a pathway linking DNA damage repair to the control of both RNAPII phosphorylation and AS regulation.

  17. Major depression

    Science.gov (United States)

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  18. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    Science.gov (United States)

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  19. Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts

    International Nuclear Information System (INIS)

    Vermeer, B.J.; Santerse, B.; Van De Kerckhove, B.A.; Schothorst, A.A.; Claas, F.H.

    1988-01-01

    The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm 2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place

  20. Coral microbial community dynamics in response to anthropogenic impacts near a major city in the central Red Sea

    KAUST Repository

    Ziegler, Maren; Roik, Anna Krystyna; Porter, Adam; Zubier, Khalid; Mudarris, Mohammed S.; Ormond, Rupert; Voolstra, Christian R.

    2016-01-01

    Coral-associated bacteria play an increasingly recognized part in coral health. We investigated the effect of local anthropogenic impacts on coral microbial communities on reefs near Jeddah, the largest city on the Saudi Arabian coast of the central Red Sea. We analyzed the bacterial community structure of water and corals (Pocillopora verrucosa and Acropora hemprichii) at sites that were relatively unimpacted, exposed to sedimentation & local sewage, or in the discharge area of municipal wastewaters. Coral microbial communities were significantly different at impacted sites: in both corals the main symbiotic taxon decreased in abundance. In contrast, opportunistic bacterial families, such as e.g. Vibrionaceae and Rhodobacteraceae, were more abundant in corals at impacted sites. In conclusion, microbial community response revealed a measurable footprint of anthropogenic impacts to coral ecosystems close to Jeddah, even though the corals appeared visually healthy.

  1. Coral microbial community dynamics in response to anthropogenic impacts near a major city in the central Red Sea

    KAUST Repository

    Ziegler, Maren

    2016-01-04

    Coral-associated bacteria play an increasingly recognized part in coral health. We investigated the effect of local anthropogenic impacts on coral microbial communities on reefs near Jeddah, the largest city on the Saudi Arabian coast of the central Red Sea. We analyzed the bacterial community structure of water and corals (Pocillopora verrucosa and Acropora hemprichii) at sites that were relatively unimpacted, exposed to sedimentation & local sewage, or in the discharge area of municipal wastewaters. Coral microbial communities were significantly different at impacted sites: in both corals the main symbiotic taxon decreased in abundance. In contrast, opportunistic bacterial families, such as e.g. Vibrionaceae and Rhodobacteraceae, were more abundant in corals at impacted sites. In conclusion, microbial community response revealed a measurable footprint of anthropogenic impacts to coral ecosystems close to Jeddah, even though the corals appeared visually healthy.

  2. Dynamic muscle O2 saturation response is impaired during major non-cardiac surgery despite goal-directed haemodynamic therapy.

    Science.gov (United States)

    Feldheiser, A; Hunsicker, O; Kaufner, L; Köhler, J; Sieglitz, H; Casans Francés, R; Wernecke, K-D; Sehouli, J; Spies, C

    2016-03-01

    Near-infrared spectroscopy combined with a vascular occlusion test (VOT) could indicate an impairment of microvascular reactivity (MVR) in septic patients by detecting changes in dynamic variables of muscle O2 saturation (StO2). However, in the perioperative context the consequences of surgical trauma on dynamic variables of muscle StO2 as indicators of MVR are still unknown. This study is a sub-analysis of a randomised controlled trial in patients with metastatic primary ovarian cancer undergoing debulking surgery, during which a goal-directed haemodynamic algorithm was applied using oesophageal Doppler. During a 3 min VOT, near-infrared spectroscopy was used to assess dynamic variables arising from changes in muscle StO2. At the beginning of surgery, values of desaturation and recovery slope were comparable to values obtained in healthy volunteers. During the course of surgery, both desaturation and recovery slope showed a gradual decrease. Concomitantly, the study population underwent a transition to a surgically induced systemic inflammatory response state shown by a gradual increase in norepinephrine administration, heart rate, and Interleukin-6, with a peak immediately after the end of surgery. Higher rates of norepinephrine and a higher heart rate were related to a faster decline in StO2 during vascular occlusion. Using near-infrared spectroscopy combined with a VOT during surgery showed a gradual deterioration of MVR in patients treated with optimal haemodynamic care. The deterioration of MVR was accompanied by the transition to a surgically induced systemic inflammatory response state. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Antibody and Cytokine Responses of Koalas (Phascolarctos cinereus) Vaccinated with Recombinant Chlamydial Major Outer Membrane Protein (MOMP) with Two Different Adjuvants

    OpenAIRE

    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...

  4. Molecular chemistry in humic Ferralsols from Brazilian Cerrado and forest biomes indicates a major contribution from black carbon in the subsoil

    NARCIS (Netherlands)

    Marques, F.A.; Buurman, P.; Schellekens, J.; Vidal-Torrado, P.

    2015-01-01

    Soil organic matter (OM) stability plays an important role in the global carbon cycle. The molecular characterisation of soil OM may contribute to an understanding of the feedback mechanisms between soil OM and climate. Umbric Ferralsols with humic properties (humic Ferralsols) are characterised by

  5. Pulmonary epithelial response in the rat lung to instilled Montserrat respirable dusts and their major mineral components.

    Science.gov (United States)

    Housley, D G; Bérubé, K A; Jones, T P; Anderson, S; Pooley, F D; Richards, R J

    2002-07-01

    The Soufriere Hills, a stratovolcano on Montserrat, started erupting in July 1995, producing volcanic ash, both from dome collapse pyroclastic flows and phreatic explosions. The eruptions/ash resuspension result in high concentrations of suspended particulate matter in the atmosphere, which includes cristobalite, a mineral implicated in respiratory disorders. To conduct toxicological studies on characterised samples of ash, together with major components of the dust mixture (anorthite, cristobalite), and a bioreactive mineral control (DQ12 quartz). Rats were challenged with a single mass (1 mg) dose of particles via intratracheal instillation and groups sacrificed at one, three, and nine weeks. Acute bioreactivity of the particles was assessed by increases in lung permeability and inflammation, changes in epithelial cell markers, and increase in the size of bronchothoracic lymph nodes. Data indicated that respirable ash derived from pyroclastic flows (20.1% cristobalite) or phreatic explosion (8.6% cristobalite) had minimal bioreactivity in the lung. Anorthite showed low bioreactivity, in contrast to pure cristobalite, which showed progressive increases in lung damage. Results suggests that either the percentage mass of cristobalite particles present in Montserrat ash was not sufficient as a catalyst in the lung environment, or its surface reactivity was masked by the non-reactive volcanic glass components during the process of ash formation.

  6. Cognitive Bias by Gender Interaction on N170 Response to Emotional Facial Expressions in Major and Minor Depression.

    Science.gov (United States)

    Wu, Xingqu; Chen, Jiu; Jia, Ting; Ma, Wentao; Zhang, Yan; Deng, Zihe; Yang, Laiqi

    2016-03-01

    States of depression are considered to relate to a cognitive bias reactivity to emotional events. Moreover, gender effect may influence differences in emotional processing. The current study is to investigate whether there is an interaction of cognitive bias by gender on emotional processing in minor depression (MiD) and major depression (MaD). N170 component was obtained during a visual emotional oddball paradigm to manipulate the processing of emotional information in 33 MiD, 36 MaD, and 32 controls (CN). Compared with CN, in male, both MiD and MaD had lower N170 amplitudes for happy faces, but MaD had higher N170 amplitudes for sad faces; in female, both MiD and MaD had lower N170 amplitudes for happy and neutral faces, but higher N170 amplitudes for sad faces. Compared with MaD in male, MiD had higher N170 amplitudes for happy faces, lower N170 amplitudes for sad faces; in female, MiD only had higher N170 amplitudes for sad faces. Interestingly, a negative relationship was observed between N170 amplitude and the HDRS score for identification of happy faces in depressed patients while N170 amplitude was positively correlated with the HDRS score for sad faces identification. These results provide novel evidence for the mood-brightening effect with an interaction of cognitive bias by gender on emotional processing. It further suggests that female depression may be more vulnerable than male during emotional face processing with the unconscious negative cognitive bias and depressive syndromes may exist on a spectrum of severity on emotional face processing.

  7. What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

    Science.gov (United States)

    Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

    2013-01-01

    A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in

  8. What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

    Directory of Open Access Journals (Sweden)

    Leticia Oliveira

    Full Text Available A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients.TWO INDEPENDENT DEPRESSED SAMPLES: (1 Nineteen medication-free patients with depression and 19 healthy volunteers and (2 Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces using data only from healthy controls (HC. Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities for emotional and neutral face classification were different for healthy controls and depressed patients.Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1 and happy faces (samples 2 between depressed patients and healthy controls.Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This

  9. 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....

  10. Molecular targets of omega 3 and conjugated linoleic fatty acids – micromanaging cellular response

    Directory of Open Access Journals (Sweden)

    Francesco eVisioli

    2012-02-01

    Full Text Available Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and CLA, as paradigmatic molecules that can be explored both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.

  11. Focusing the HIV response through estimating the major modes of HIV transmission: a multi-country analysis

    Science.gov (United States)

    Gouws, Eleanor; Cuchi, Paloma

    2012-01-01

    Objective An increasing number of countries have been estimating the distribution of new adult HIV infections by modes of transmission (MOT) to help prioritise prevention efforts. We compare results from studies conducted between 2008 and 2012 and discuss their use for planning and responding to the HIV epidemic. Methods The UNAIDS recommended MOT model helps countries to estimate the proportion of new HIV infections that occur through key transmission modes including sex work, injecting drug use (IDU), men having sex with men (MSM), multiple sexual partnerships, stable relationships and medical interventions. The model typically forms part of a country-led process that includes a comprehensive review of epidemiological data. Recent revisions to the model are described. Results Modelling results from 25 countries show large variation between and within regions. In sub-Saharan Africa, new infections occur largely in the general heterosexual population because of multiple partnerships or in stable discordant relationships, while sex work contributes significantly to new infections in West Africa. IDU and sex work are the main contributors to new infections in the Middle East and North Africa, with MSM the main contributor in Latin America. Patterns vary substantially between countries in Eastern Europe and Asia in terms of the relative contribution of sex work, MSM, IDU and spousal transmission. Conclusions The MOT modelling results, comprehensive review and critical assessment of data in a country can contribute to a more strategically focused HIV response. To strengthen this type of research, improved epidemiological and behavioural data by risk population are needed. PMID:23172348

  12. Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum.

    Science.gov (United States)

    Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tenma, Natsuki; Inai, Makoto; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

    2016-07-01

    The importance of ethanol oxidation by intestinal aerobes and facultative anaerobes under aerobic conditions in the pathogenesis of ethanol-related colorectal cancer has been proposed. However, the role of obligate anaerobes therein remains to be established, and it is still unclear which bacterial species, if any, are most important in the production and/or elimination of carcinogenic acetaldehyde under such conditions. This study was undertaken to address these issues. More than 500 bacterial strains were isolated from the faeces of Japanese alcoholics and phylogenetically characterized, and their aerobic ethanol metabolism was studied in vitro to examine their ability to accumulate acetaldehyde beyond the minimum mutagenic concentration (MMC, 50 µM). Bacterial strains that were considered to potentially accumulate acetaldehyde beyond the MMC under aerobic conditions in the colon and rectum were identified and referred to as 'potential acetaldehyde accumulators' (PAAs). Ruminococcus, an obligate anaerobe, was identified as a genus that includes a large number of PAAs. Other obligate anaerobes were also found to include PAAs. The accumulation of acetaldehyde by PAAs colonizing the colorectal mucosal surface could be described, at least in part, as the response of PAAs to oxidative stress. Ethanol oxidation by intestinal obligate anaerobes under aerobic conditions in the colon and rectum could also play an important role in the pathogenesis of ethanol-related colorectal cancer. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  13. 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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. 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.

  18. Molecular correlates of impaired prefrontal plasticity in response to chronic stress

    NARCIS (Netherlands)

    Kuipers, SD; Trentani, A; Den Boer, JA; Ter Horst, GJ

    Disturbed adaptations at the molecular and cellular levels following stress could represent compromised neural plasticity that contributes to the pathophysiology of stress-induced disorders. Evidence illustrates atrophy and cell death of stress-vulnerable neurones in the prefrontal cortex. Reduced

  19. Fast transient current response to switching events in short chains of molecular islands

    Czech Academy of Sciences Publication Activity Database

    Kalvová, Anděla; Špička, Václav; Velický, B.

    2013-01-01

    Roč. 26, č. 4 (2013), s. 773-777 ISSN 1557-1939 R&D Projects: GA ČR GAP204/12/0897 Institutional support: RVO:68378271 Keywords : nonequilibrium * molecular islands * initial correlations * transient currents Subject RIV: BE - Theoretical Physics Impact factor: 0.930, year: 2013

  20. ART culture conditions change the probability of mouse embryo gestation through defined cellular and molecular responses.

    Science.gov (United States)

    Schwarzer, Caroline; Esteves, Telma Cristina; Araúzo-Bravo, Marcos J; Le Gac, Séverine; Nordhoff, Verena; Schlatt, Stefan; Boiani, Michele

    2012-09-01

    Do different human ART culture protocols prepare embryos differently for post-implantation development? The type of ART culture protocol results in distinct cellular and molecular phenotypes in vitro at the blastocyst stage as well as subsequently during in vivo development. It has been reported that ART culture medium affects human development as measured by gestation rates and birthweights. However, due to individual variation across ART patients, it is not possible as yet to pinpoint a cause-effect relationship between choice of culture medium and developmental outcome. In a prospective study, 13 human ART culture protocols were compared two at a time against in vivo and in vitro controls. Superovulated mouse oocytes were fertilized in vivo using outbred and inbred mating schemes. Zygotes were cultured in medium or in the oviduct and scored for developmental parameters 96 h later. Blastocysts were either analyzed or transferred into fosters to measure implantation rates and fetal development. In total, 5735 fertilized mouse oocytes, 1732 blastocysts, 605 fetuses and 178 newborns were examined during the course of the study (December 2010-December 2011). Mice of the B6C3F1, C57Bl/6 and CD1 strains were used as oocyte donors, sperm donors and recipients for embryo transfer, respectively. In vivo fertilized B6C3F1 oocytes were allowed to cleave in 13 human ART culture protocols compared with mouse oviduct and optimized mouse medium (KSOM(aa)). Cell lineage composition of resultant blastocysts was analyzed by immunostaining and confocal microscopy (trophectoderm, Cdx2; primitive ectoderm, Nanog; primitive endoderm, Sox17), global gene expression by microarray analysis, and rates of development to midgestation and to term. Mouse zygotes show profound variation in blastocyst (49.9-91.9%) and fetal (15.7-62.0%) development rates across the 13 ART culture protocols tested (R(2)= 0.337). Two opposite protocols, human tubal fluid/multiblast (high fetal rate) and ISM1/ISM2

  1. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Katherine E Tansey

    Full Text Available It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study. After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8. No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8 were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D, with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the

  2. 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.

  3. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis.

    Science.gov (United States)

    Tansey, Katherine E; Guipponi, Michel; Perroud, Nader; Bondolfi, Guido; Domenici, Enrico; Evans, David; Hall, Stephanie K; Hauser, Joanna; Henigsberg, Neven; Hu, Xiaolan; Jerman, Borut; Maier, Wolfgang; Mors, Ole; O'Donovan, Michael; Peters, Tim J; Placentino, Anna; Rietschel, Marcella; Souery, Daniel; Aitchison, Katherine J; Craig, Ian; Farmer, Anne; Wendland, Jens R; Malafosse, Alain; Holmans, Peter; Lewis, Glyn; Lewis, Cathryn M; Stensbøl, Tine Bryan; Kapur, Shitij; McGuffin, Peter; Uher, Rudolf

    2012-01-01

    It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way. The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance panalysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D. No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.

  4. 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.

  5. Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study

    Directory of Open Access Journals (Sweden)

    Park YM

    2016-05-01

    Full Text Available Young-Min Park,1 Bun-Hee Lee2 1Department of Psychiatry, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 2Department of Psychiatry, Seoul Eunpyeong Hospital, Seoul, Republic of Korea Background: The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD monotherapy over a 6-month follow-up period. Methods: Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ, which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points. They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI, Hamilton Depression Rating Scale (HAMD, Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. Results: The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. Conclusion: The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity. Keywords: subthreshold bipolarity

  6. 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.

  7. 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

  8. 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.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Molecular mechanisms governing differential robustness of development and environmental responses in plants

    DEFF Research Database (Denmark)

    Lachowiec, Jennifer; Queitsch, Christine; Kliebenstein, Daniel James

    2016-01-01

    -genome duplications, tandem gene duplication and hybridization are emerging as major regulators of robustness in development. Despite their obvious implications for plant evolution and plant breeding, the mechanistic underpinnings by which plants modulate precise levels of robustness, plasticity and evolvability...

  13. Simulated dynamic response of a multi-stage compressor with variable molecular weight flow medium

    Science.gov (United States)

    Babcock, Dale A.

    1995-01-01

    A mathematical model of a multi-stage compressor with variable molecular weight flow medium is derived. The modeled system consists of a five stage, six cylinder, double acting, piston type compressor. Each stage is followed by a water cooled heat exchanger which serves to transfer the heat of compression from the gas. A high molecular weight gas (CFC-12) mixed with air in varying proportions is introduced to the suction of the compressor. Condensation of the heavy gas may occur in the upper stage heat exchangers. The state equations for the system are integrated using the Advanced Continuous Simulation Language (ACSL) for determining the system's dynamic and steady state characteristics under varying operating conditions.

  14. Molecular-scale shear response of the organic semiconductor β -DBDCS (100) surface

    Science.gov (United States)

    Álvarez-Asencio, Rubén; Moreno-Ramírez, Jorge S.; Pimentel, Carlos; Casado, Santiago; Matta, Micaela; Gierschner, Johannes; Muccioli, Luca; Yoon, Seong-Jun; Varghese, Shinto; Park, Soo Young; Gnecco, Enrico; Pina, Carlos M.

    2017-09-01

    In this work we present friction-force microscopy (FFM) lattice-resolved images acquired on the (100) facet of the semiconductor organic oligomer (2 Z ,2'Z )-3 , 3' -(1,4-phenylene)bis(2-(4-butoxyphenyl)acrylonitrile) (β -DBDCS) crystal in water at room temperature. Stick-slip contrast, lateral contact stiffness, and friction forces are found to depend strongly on the sliding direction due to the anisotropic packing of the molecular chains forming the crystal surface along the [010] and [001] directions. The anisotropy also causes the maximum value of the normal force applicable before wearing to increase by a factor of 3 when the scan is performed along the [001] direction on the (100) face. Altogether, our results contribute to achieving a better understanding of the molecular origin of friction anisotropy on soft crystalline surfaces, which has been often hypothesized but rarely investigated in the literature.

  15. ‘Mom—I don’t want to hear it’: Brain response to maternal praise and criticism in adolescents with major depressive disorder

    Science.gov (United States)

    Lee, Kyung Hwa; Elliott, Rosalind D.; Hooley, Jill M.; Dahl, Ronald E.; Barber, Anita; Siegle, Greg J.

    2017-01-01

    Abstract Recent research has implicated altered neural response to interpersonal feedback as an important factor in adolescent depression, with existing studies focusing on responses to feedback from virtual peers. We investigated whether depressed adolescents differed from healthy youth in neural response to social evaluative feedback from mothers. During neuroimaging, twenty adolescents in a current episode of major depressive disorder (MDD) and 28 healthy controls listened to previously recorded audio clips of their own mothers’ praise, criticism and neutral comments. Whole-brain voxelwise analyses revealed that MDD youth, unlike controls, exhibited increased neural response to critical relative to neutral clips in the parahippocampal gyrus, an area involved in episodic memory encoding and retrieval. Depressed adolescents also showed a blunted response to maternal praise clips relative to neutral clips in the parahippocampal gyrus, as well as areas involved in reward and self-referential processing (i.e. ventromedial prefrontal cortex, precuneus, and thalamus/caudate). Findings suggest that maternal criticism may be more strongly encoded or more strongly activated during memory retrieval related to previous autobiographical instances of negative feedback from mothers in depressed youth compared to healthy youth. Furthermore, depressed adolescents may fail to process the reward value and self-relevance of maternal praise. PMID:28338795

  16. 'Mom-I don't want to hear it': Brain response to maternal praise and criticism in adolescents with major depressive disorder.

    Science.gov (United States)

    Silk, Jennifer S; Lee, Kyung Hwa; Elliott, Rosalind D; Hooley, Jill M; Dahl, Ronald E; Barber, Anita; Siegle, Greg J

    2017-05-01

    Recent research has implicated altered neural response to interpersonal feedback as an important factor in adolescent depression, with existing studies focusing on responses to feedback from virtual peers. We investigated whether depressed adolescents differed from healthy youth in neural response to social evaluative feedback from mothers. During neuroimaging, twenty adolescents in a current episode of major depressive disorder (MDD) and 28 healthy controls listened to previously recorded audio clips of their own mothers' praise, criticism and neutral comments. Whole-brain voxelwise analyses revealed that MDD youth, unlike controls, exhibited increased neural response to critical relative to neutral clips in the parahippocampal gyrus, an area involved in episodic memory encoding and retrieval. Depressed adolescents also showed a blunted response to maternal praise clips relative to neutral clips in the parahippocampal gyrus, as well as areas involved in reward and self-referential processing (i.e. ventromedial prefrontal cortex, precuneus, and thalamus/caudate). Findings suggest that maternal criticism may be more strongly encoded or more strongly activated during memory retrieval related to previous autobiographical instances of negative feedback from mothers in depressed youth compared to healthy youth. Furthermore, depressed adolescents may fail to process the reward value and self-relevance of maternal praise. © The Author (2017). Published by Oxford University Press.

  17. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa.

    Science.gov (United States)

    Riveron, Jacob M; Ibrahim, Sulaiman S; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J; Ishak, Intan H; Wondji, Charles S

    2017-06-07

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes ( CYP6P9a and CYP6P9b ) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. Copyright © 2017 Riveron et al.

  18. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa

    Science.gov (United States)

    Riveron, Jacob M.; Ibrahim, Sulaiman S.; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J.; Ishak, Intan H.; Wondji, Charles S.

    2017-01-01

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. PMID:28428243

  19. Sex differences in the prediction of the effectiveness of paroxetine for patients with major depressive disorder identified using a receiver operating characteristic curve analysis for early response.

    Science.gov (United States)

    Tomita, Tetsu; Yasui-Furukori, Norio; Norio, Yasui-Furukori; Sato, Yasushi; Nakagami, Taku; Tsuchimine, Shoko; Kaneda, Ayako; Kaneko, Sunao

    2014-01-01

    We investigated cutoff values for the early response of patients with major depressive disorder to paroxetine and their sex differences by using a receiver operating characteristic (ROC) curve analysis to predict the effectiveness of paroxetine. In total, 120 patients with major depressive disorder were enrolled and treated with 10-40 mg/day paroxetine for 6 weeks; 89 patients completed the protocol. A clinical evaluation using the Montgomery-Asberg Depression Rating Scale (MADRS) was performed at weeks 0, 1, 2, 4, and 6. In male subjects, the cutoff values for MADRS improvement rating in week 1, week 2, and week 4 were 20.9%, 34.9%, and 33.3%, respectively. The sensitivities and the specificities were 83.3% and 80.0%, 83.3% and 80.0%, and 100% and 90%, respectively. The areas under the curve (AUC) were 0.908, 0.821, and 0.979, respectively. In female subjects, the cutoff values for the MADRS improvement rating in week 1, week 2, and week 4 were 21.4%, 35.7%, and 32.3%, respectively. The sensitivities and the specificities were 71.4% and 84.6%, 73.8% and 76.9%, and 90.5% and 76.9%, respectively. The AUCs were 0.781, 0.735, and 0.904, respectively. Early improvement with paroxetine may predict the long-term response. The accuracy of the prediction for the response is higher in male subjects.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections

    NARCIS (Netherlands)

    M.H.T. Stappers (Mark H. T.); F. Hagen (Ferry); P. Reimnitz (Peter); J.W. Mouton (Johan); J.F. Meis (Jacques F.); I.C. Gyssens (Inge)

    2015-01-01

    textabstractMajor abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and β-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific

  6. Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections

    NARCIS (Netherlands)

    Stappers, M.H.T.; Hagen, F.; Reimnitz, P.; Mouton, J.W.; Meis, J.F.; Gyssens, I.C.J.

    2015-01-01

    Major abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and beta-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific real-time

  7. Molecular mechanisms involved in adaptive responses to radiation, UV light, and heat

    International Nuclear Information System (INIS)

    Takahashi, Akihisa; Ohnishi, Takeo

    2009-01-01

    Viable organisms recognize and respond to environmental changes or stresses. When these environmental changes and their responses by organisms are extreme, they can limit viability. However, organisms can adapt to these different stresses by utilizing different possible responses via signal transduction pathways when the stress is not lethal. In particular, prior mild stresses can provide some aid to prepare organisms for subsequent more severe stresses. These adjustments or adaptations for future stresses have been called adaptive responses. These responses are present in bacteria, plants and animals. The following review covers recent research which can help describe or postulate possible mechanisms which may be active in producing adaptive responses to radiation, ultraviolet light, and heat. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. A remarkable hematological and molecular response pattern in a patient with polycythemia vera during combination therapy with simvastatin and alendronate

    Directory of Open Access Journals (Sweden)

    Anders Lindholm Sørensen

    2016-01-01

    Full Text Available We report a 57-year old man with polycythemia vera, who had a remarkable hematological and molecular response during treatment with simvastatin and alendronate. The patient was treated with this combination for 56 months, and during this period the patient has been in complete hematological remission. The JAK2-V617F allele burden has dropped from 64% to sustained values below 20%, and follow-up bone marrow biopsies have revealed no change in PV features, without any regular cytoreductive treatment.

  11. [Management strategies for major depressive episodes as a function of initial response to an SSRI or SNRI antidepressant: results of the ORACLE survey].

    Science.gov (United States)

    Spadone, C; Sylvestre, M; Chiarelli, P; Richard-Berthe, C

    2005-01-01

    The main aim of the major depressive episode treatment is to obtain a complete remission. However, partial remission (persistence of residual symptoms) is a frequent outcome of major depressive episodes, concerning approximately half of the patients who were responders to the treatment. An inadequate treatment response after three weeks of treatment is considered by the ANAES recommendations as a potential reason to modify the treatment regimen. The primary objectives of this survey were to describe the therapeutic strategies implemented in subjects treated as outpatients for a major depressive episode following evaluation of the initial response to an SSRI or an SNRI antidepressant and to assess by a naturalistic way the impact of these strategies on the extent of remission at three months. The secondary objective was to determine, by multivariate analysis, others factors able to influence the remission. This prospective observational survey concerned 2 138 patients treated by community psychiatrists (n=582) and presenting a major depressive episode in the context of a recurrent depressive disorder. Patients were assessed at inclusion and at Weeks 3, at Week 6 and at Week 12. Changes in score on the Hamilton Depression Scale (Ham-D) and CGI severity between inclusion and Week 3 and improvement scores were evaluated. The therapeutic strategies after evaluation were described. Remission was defined as a score of 1 or 2 on the CGI-improvement scale; a treatment response at Week 3 was defined as a decrease of at least 50% in the Ham-D score. The physician also provided an overall rating of satisfaction with the treatment at Week 3. Data from 1 974 patients were analysed. The mean age at inclusion was 42.7 years, 70% of the patients were women; the mean age at first episode was 32.2 years, the average time since the last episode was 3.6 years. The mean Ham-D score at inclusion was 23.6 +/- 5.8. At Week 3, 29.1% of patients were considered treatment responders. The

  12. Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

    Science.gov (United States)

    Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

    2017-01-01

    A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    International Nuclear Information System (INIS)

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-01-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  14. Incipient plasticity and indentation response of MgO surfaces using molecular dynamics

    Science.gov (United States)

    Tran, Anh-Son; Hong, Zheng-Han; Chen, Ming-Yuan; Fang, Te-Hua

    2018-05-01

    The mechanical characteristics of magnesium oxide (MgO) based on nanoindentation are studied using molecular dynamics (MD) simulation. The effects of indenting speed and temperature on the structural deformation and loading-unloading curve are investigated. Results show that the strained surface of the MgO expands to produce a greater relaxation of atoms in the surroundings of the indent. The dislocation propagation and pile-up for MgO occur more significantly with the increasing temperature from 300 K to 973 K. In addition, with increasing temperature, the high strained atoms with a great perturbation appearing at the groove location.

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

    Science.gov (United States)

    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.

  16. Molecular study of the dentin-pulp complex responses to caries progression

    Directory of Open Access Journals (Sweden)

    Yani Corvianindya Rahayu

    2007-03-01

    Full Text Available The dentin-pulp complex exhibits various responses to caries, including events of injury, defense, and repair. The overall responses dependent on pulp cell activity and the signaling processes, which regulate the behavior of these cells. The signals for tissue repair are thought to be mediated by dentin-bound growth factors released during caries progression. Growth factors are a key of molecules responsible for signaling a variety of cellular process following dental injury. The endogenous proteolytic enzymes (Matrix metalloproteinases, MMPs present in dentin matrix might also participate in releasing bioactive molecule. Several members of the MMP family are found in the soft and hard tissue compartment of dentin-pulp complex. Their presumed role in many physiological process during the development and maintenance of the dentin-pulp complex, they may also contribute to the pathogenesis of dentin caries and the responses elicited by caries.

  17. MYR1-Dependent Effectors Are the Major Drivers of a Host Cell’s Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects

    Directory of Open Access Journals (Sweden)

    Adit Naor

    2018-04-01

    Full Text Available The obligate intracellular parasite Toxoplasma gondii controls its host cell from within the parasitophorous vacuole (PV by using a number of diverse effector proteins, a subset of which require the aspartyl protease 5 enzyme (ASP5 and/or the recently discovered MYR1 protein to cross the PV membrane. To examine the impact these effectors have in the context of the entirety of the host response to Toxoplasma, we used RNA-Seq to analyze the transcriptome expression profiles of human foreskin fibroblasts infected with wild-type RH (RH-WT, RHΔmyr1, and RHΔasp5 tachyzoites. Interestingly, the majority of the differentially regulated genes responding to Toxoplasma infection are MYR1 dependent. A subset of MYR1 responses were ASP5 independent, and MYR1 function did not require ASP5 cleavage, suggesting the export of some effectors requires only MYR1. Gene set enrichment analysis of MYR1-dependent host responses suggests an upregulation of E2F transcription factors and the cell cycle and a downregulation related to interferon signaling, among numerous others. Most surprisingly, “hidden” responses arising in RHΔmyr1- but not RH-WT-infected host cells indicate counterbalancing actions of MYR1-dependent and -independent activities. The host genes and gene sets revealed here to be MYR1 dependent provide new insight into the parasite’s ability to co-opt host cell functions.

  18. Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

    Science.gov (United States)

    Yang, Xin-hua; Huang, Jia; Lan, Yong; Zhu, Cui-ying; Liu, Xiao-qun; Wang, Ye-fei; Cheung, Eric F C; Xie, Guang-rong; Chan, Raymond C K

    2016-01-04

    Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

    Science.gov (United States)

    Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

    2010-12-01

    Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. 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.

  1. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  2. Molecular and cellular responses to renal injury : a (phospho)-proteomic approach

    NARCIS (Netherlands)

    Graauw, Marjo de

    2007-01-01

    Our kidneys play a major role in regulating the body’s internal environment, via transportation of water, salt, potassium and waste products. As a result of this transport function, cells within the kidney are relatively sensitive to injury. This injury can occur when the kidneys are exposed to

  3. Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

    Science.gov (United States)

    Redgrove, Kate A.; McLaughlin, Eileen A.

    2017-01-01

    In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte. PMID:29312475

  4. 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.

  5. The NAC transcription factor family in maritime pine (Pinus Pinaster): molecular regulation of two genes involved in stress responses.

    Science.gov (United States)

    Pascual, Ma Belén; Cánovas, Francisco M; Ávila, Concepción

    2015-10-24

    NAC transcription factors comprise a large plant-specific gene family involved in the regulation of diverse biological processes. Despite the growing number of studies on NAC transcription factors in various species, little information is available about this family in conifers. The goal of this study was to identify the NAC transcription family in maritime pine (Pinus pinaster), to characterize ATAF-like genes in response to various stresses and to study their molecular regulation. We have isolated two maritime pine NAC genes and using a transient expression assay in N. benthamiana leaves estudied the promoter jasmonate response. In this study, we identified 37 NAC genes from maritime pine and classified them into six main subfamilies. The largest group includes 12 sequences corresponding to stress-related genes. Two of these NAC genes, PpNAC2 and PpNAC3, were isolated and their expression profiles were examined at various developmental stages and in response to various types of stress. The expression of both genes was strongly induced by methyl jasmonate (MeJA), mechanical wounding, and high salinity. The promoter regions of these genes were shown to contain cis-elements involved in the stress response and plant hormonal regulation, including E-boxes, which are commonly found in the promoters of genes that respond to jasmonate, and binding sites for bHLH proteins. Using a transient expression assay in N. benthamiana leaves, we found that the promoter of PpNAC3 was rapidly induced upon MeJA treatment, while this response disappeared in plants in which the transcription factor NbbHLH2 was silenced. Our results suggest that PpNAC2 and PpNAC3 encode stress-responsive NAC transcription factors involved in the jasmonate response in pine. Furthermore, these data also suggest that the jasmonate signaling pathway is conserved between angiosperms and gymnosperms. These findings may be useful for engineering stress tolerance in pine via biotechnological approaches.

  6. Photosynthesis and biochemical responses to elevated O3 in Plantago major and Sonchus oleraceus growing in a lowland habitat of northern China.

    Science.gov (United States)

    Su, Benying; Zhou, Meihua; Xu, Hong; Zhang, Xiujie; Li, Yonggeng; Su, Hua; Xiang, Bao

    2017-03-01

    A field experiment was carried out to compare the responses to ozone (O 3 ) in two common herbaceous plant species, Plantago major L. and Sonchus oleraceus L., by building open-top growth chambers in situ to simulate O 3 stress (+O 3 , 85±5ppb, 9hr/day for 30days) in a lowland habitat in Inner Mongolia, Northern China. Responses to O 3 of gas exchange, chlorophyll a fluorescence, leaf pigment content, antioxidant capability, soluble protein content, membrane lipid peroxidation and dark respiration (R d ) were analyzed. Results showed that elevated O 3 exposure significantly reduced the light-saturated net photosynthesis (P Nsat ), stomatal conductance (g s ) and transpiration rate (E) in both species. Although non-significant interactive effect between species and O 3 on P Nsat was analyzed, the reduction in P Nsat in S. oleraceus might be due primarily to the higher fraction of close PSII reaction centers and impaired activities of plant mesophyll cells as evidences by decreased maximum efficiency of PSII photochemistry after dark adapted state (F v /F m ) and unchanged intercellular CO 2 concentration (C i ). Besides, biochemical analysis showed that S. oleraceus had lower antioxidant ability compared to P. major. As a result, S. oleraceus was damaged to the larger extent in terms of lipid peroxidation and visible O 3 injury, indicating that S. oleraceus was more sensitive to O 3 than P. major. Our results indicated that wild herbaceous plant species growing in a lowland habitat in sandy grassland were sensitive to O 3 stress and S. oleraceus can be considered as one of the bio-indicators for high O 3 concentration in semi-arid grassland of northern China. Copyright © 2016. Published by Elsevier B.V.

  7. Hybridization improved bacteria resistance in abalone: Evidence from physiological and molecular responses.

    Science.gov (United States)

    Liang, Shuang; Luo, Xuan; You, Weiwei; Ke, Caihuan

    2018-01-01

    Hybridization is an effective way of improving germplasm in abalone, as it often generates benign traits in the hybrids. The hybrids of Haliotis discus hannai and H. gigantea have shown heterosis in terms of disease resistance than one or both parental species. In the present study, to elucidate the physiological and molecular mechanism of this heterosis, we analyzed the dynamic changes of several immune indexes including survival rate, total circulating haemocyte count (THC), phagocytic activity, reactive oxygen species level (ROS) and phenoloxidase activity (PO) in two parental species, H. discus hannai (DD) and H. gigantea (GG), and their reciprocal hybrids H. discus hannai ♀ × H. gigantea ♂ (DG), H. gigantea ♀ × H. discus hannai ♂ (GD) challenged with a mixture of Vibrio harveyi, V. alginolyticus and V. parahaemolyticus (which have been demonstrated to be pathogenic to abalone). Besides, we cloned and analyzed three important immune genes: heat shock protein 70 (hsp70), ferritin and cold shock domain protein (csdp) in H. discus hannai and H. gigantea, then further investigated their mRNA level changes in the four abalone genotypes after bacterial challenge. Results showed that these physiological and molecular parameters were significantly induced by bacterial exposure, and their changing patterns were obviously different between the four genotypes: (1) Survival rates of the two hybrids were higher than both parental species after bacterial exposure; (2) DG had higher THC than the other three genotypes; (3) Phagocytosis responded slower in the hybrids than in the parental species; (4) DD's ROS level was lower than the other three genotypes at 48 h post infection; (5) Phenoloxidase activity was lower in DD during the infection compared to the other genotypes; (6) mRNA levels of hsp70 and csdp, were always lower in at least one parental species (DD) than in the hybrids after the bacterial exposure. Results from this study indicate that the hybrids

  8. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi's anemia

    International Nuclear Information System (INIS)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F.

    1997-01-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to γ-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  9. Cellular and molecular response to irradiation in ataxia telangiectasia and in Fanconi`s anemia

    Energy Technology Data Exchange (ETDEWEB)

    Ridet, A.; Guillouf, C.; Duchaud, E.; Moustacchi, E.; Rosselli, F. [Institut Curie-Recherche, UMR 218, CNRS, 75 - Paris (France)

    1997-03-01

    Ataxia telangiectasia (AT) and Fanconi anemia (FA) are recessive genetic diseases featuring chromosomal instability, increased predisposition to cancer and in vitro hypersensitivity to ionizing radiation (AT) or DNA cross-linking agents (FA). Moreover, an in vivo hypersensitivity to {gamma}-rays exposure was reported in both syndromes. Cellular response to irradiation includes growth arrest (cell cycle modification) and cell death (by apoptosis or necrosis). Since it is generally accepted that apoptosis modulates cellular sensitivity to genotoxic stress, it was of interest to investigate the contribution of apoptosis in determining FA and AT responses to DNA Damaging Agents. The results support the contention that the in vivo hypersensitivity to radiation in these syndromes is not related to a higher rate of apoptotic cells but could be to a higher necrotic response triggering inflammatory reactions in the patients affected by this syndromes. (authors)

  10. Health effects of low-dose radiation: Molecular, cellular, and biosystem response

    International Nuclear Information System (INIS)

    Pollycove, M.; Paperiello, C.J.

    1997-01-01

    Since the fifties, the prime concern of radiation protection has been protecting DNA from damage. UNSCEAR initiated a focus on biosystem response to damage with its 1994 report, ''Adaptive Responses to Radiation of Cells and Organisms''. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation induced damage, both effected predominantly by free radicals. These adaptive responses are suppressed by high-dose and stimulated by low dose radiation. Increased biosystem efficiently reduces the number of mutations that accumulate during a lifetime and decrease DNA damage-control with resultant aging and malignancy. Several statistically significant epidemiologic studies have shown risk decrements of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Further biologic and epidemiologic research is needed to establish a valid threshold below which risk decrements occur. (author)

  11. Biological profiling of prospective antidepressant response in major depressive disorder: Associations with (neuro)inflammation, fatty acid metabolism, and amygdala-reactivity.

    Science.gov (United States)

    Mocking, R J T; Nap, T S; Westerink, A M; Assies, J; Vaz, F M; Koeter, M W J; Ruhé, H G; Schene, A H

    2017-05-01

    A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown. To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response. We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks). Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study. Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in

  12. Identification of treatment response predictors and potential molecular targets for chemo preventive and antiangiogenic therapies

    International Nuclear Information System (INIS)

    Pfeffer, U.; Albini, A.

    2009-01-01

    The aims of the project were: To evaluate the cellular responses to anti-inflammatory and anti-angiogenic natural or synthetic compounds (chemo preventives, inhibitors of cell survival and inflammation related signal transduction). To identify bio markers for treatment response through the selection of targets that are common to or specific for anti-inflammatory and anti-angiogenic activities. To analyze the regulation of the key tumor-promotion pathways Akt, HIF1α, NFκB. We focused our studies on the antiapoptotic role of the AKT survival pathway, which is involved in prostate tumor progression to an androgen-independent phenotype

  13. Variations of Climate-Growth Response of Major Conifers at Upper Distributional Limits in Shika Snow Mountain, Northwestern Yunnan Plateau, China

    Directory of Open Access Journals (Sweden)

    Yun Zhang

    2017-10-01

    Full Text Available Improved understanding of climate-growth relationships of multiple species is fundamental to understanding and predicting the response of forest growth to future climate change. Forests are mainly composed of conifers in Northwestern Yunnan Plateau, but variations of growth response to climate conditions among the species are not well understood. To detect the growth response of multiple species to climate change, we developed residual chronologies of four major conifers, i.e., George’s fir (Abies georgei Orr, Likiang spruce (Picea likiangensis (Franch. E.Pritz., Gaoshan pine (Pinus densata Mast. and Chinese larch (Larix potaninii Batalin at the upper distributional limits in Shika Snow Mountain. Using the dendroclimatology method, we analyzed correlations between the residual chronologies and climate variables. The results showed that conifer radial growth was influenced by both temperature and precipitation in Shika Snow Mountain. Previous November temperature, previous July temperature, and current May precipitation were the common climatic factors that had consistent influences on radial growth of the four species. Temperature in the previous post-growing season (September–October and moisture conditions in the current growing season (June–August were the common climatic factors that had divergent impacts on the radial growth of the four species. Based on the predictions of climate models and our understanding of the growth response of four species to climate variables, we may understand the growth response to climate change at the species level. It is difficult to predict future forest growth in the study area, since future climate change might cause both increases and decreases for the four species and indirect effects of climate change on forests should be considered.

  14. Humoral immune responses in koalas (Phascolarctos cinereus) either naturally infected with Chlamydia pecorum or following administration of a recombinant chlamydial major outer membrane protein vaccine.

    Science.gov (United States)

    Khan, Shahneaz Ali; Polkinghorne, Adam; Waugh, Courtney; Hanger, Jon; Loader, Jo; Beagley, Kenneth; Timms, Peter

    2016-02-03

    The development of a vaccine is a key strategy to combat the widespread and debilitating effects of chlamydial infection in koalas. One such vaccine in development uses recombinant chlamydial major outer membrane protein (rMOMP) as an antigen and has shown promising results in several koala trials. Previous chlamydial vaccine studies, primarily in the mouse model, suggest that both cell-mediated and antibody responses will be required for adequate protection. Recently, the important protective role of antibodies has been highlighted. In our current study, we conducted a detailed analysis of the antibody-mediated immune response in koalas that are either (a) naturally-infected, and/or (b) had received an rMOMP vaccine. Firstly, we observed that naturally-infected koalas had very low levels of Chlamydia pecorum-specific neutralising antibodies. A strong correlation between low IgG total titers/neutralising antibody levels, and higher C. pecorum infection load was also observed in these naturally-infected animals. In vaccinated koalas, we showed that the vaccine was able to boost the humoral immune response by inducing strong levels of C. pecorum-specific neutralising antibodies. A detailed characterisation of the MOMP epitope response was also performed in naturally-infected and vaccinated koalas using a PepScan epitope approach. This analysis identified unique sets of MOMP epitope antibodies between naturally-infected non-protected and diseased koalas, versus vaccinated koalas, with the latter group of animals producing a unique set of specific epitope-directed antibodies that we demonstrated were responsible for the in vitro neutralisation activity. Together, these results show the importance of antibodies in chlamydial infection and immunity following vaccination in the koala. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Huamani, Jessica; Fu, Allie; Hallahan, Dennis E.

    2006-01-01

    The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer

  16. Morphological, histopathological and molecular characterization of Thelohanellus theinensis n. sp. (Cnidaria: Myxosporea) infecting an Indian major carp, Labeo bata in a cold water wetland in Punjab (India).

    Science.gov (United States)

    Gupta, Aditya; Kaur, Harpreet

    2017-09-01

    A myxozoan parasite belonging to the genus Thelohanellus Kudo, 1933 (Myxosporea, Bivalvulida) was isolated from the gill lamellae of Labeo bata (Hamilton, 1822) inhabiting Ranjit Sagar Wetland in Northern parts of Punjab, India. Histopathology of the infected gills indicated lamellar distortion due to the presence of plasmodia. The intensity of infection was recorded to be moderate as indicated by gill plasmodial index (GPI = 2). The plasmodia were microscopic, ovoid, creamish white, 2.0-4.0 mm in diameter containing 300-400 number of myxospores. The myxospores were broadly pyriform in shape, measuring 8.27 × 4.41 µm, having a prominent pore at the anterior end. The polar capsule was pyriform in shape, measuring 4.15 × 4.10 µm, containing a polar filament coiled perpendicular to the longitudinal axis of myxospore body making 6-7 turns. At molecular level, the analysis of 18S rDNA sequence of T. theinensis n. sp. demonstrated maximum homogeneity of 99 % with T. filli (KR340464) as only 2 gaps were found due to the difference of the last 20 base pairs at the 3' end of T. theinensis n. sp. The current study emphasizes the need for caution when dealing with members of species complex.

  17. 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

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

    Czech Academy of Sciences Publication Activity Database

    Bardhan, J. P.; Jungwirth, Pavel; Makowski, L.

    Roč. 137, č. 12 ( 2012 ), 124101/1-124101/6 ISSN 0021-9606 R&D Projects: GA MŠk LH12001 Institutional research plan: CEZ:AV0Z40550506 Keywords : ion solvation * continuum models * linear response Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.164, year: 2012

  19. Methanol and ethanol modulate responses to danger- and microbe-associated molecular patterns

    Science.gov (United States)

    Methanol is a byproduct of cell wall modification, released through the action of pectin methylesterases (PMEs), which demethylesterify cell wall pectins. Plant PMEs play not only a role in developmental processes but also in responses to herbivory and infection by fungal or bacterial pathogens. Mol...

  20. The molecular mechanism of zinc and cadmium stress response in plants

    NARCIS (Netherlands)

    Lin, Y.F.; Aarts, M.G.M.

    2012-01-01

    When plants are subjected to high metal exposure, different plant species take different strategies in response to metal-induced stress. Largely, plants can be distinguished in four groups: metal-sensitive species, metal-resistant excluder species, metal-tolerant non-hyperaccumulator species, and

  1. Integrating Responsible Conduct of Research Education into Undergraduate Biochemistry and Molecular Biology Laboratory Curricula

    Science.gov (United States)

    Hendrickson, Tamara L.

    2015-01-01

    Recently, a requirement for directed responsible conduct in research (RCR) education has become a priority in the United States and elsewhere. In the US, both the National Institutes of Health and the National Science Foundation require RCR education for all students who are financially supported by federal awards. The guidelines produced by these…

  2. Propagating Molecular Recognition Events through Highly Integrated Sense-Response Chemical Systems

    Science.gov (United States)

    2017-08-01

    Gianneschi: 2015 Outstanding Young Scientist Award, ACS Applied Materials & Interfaces, PAT 2015 2016 Fellow of the Royal Society of Chemistry 2016...Tianfu Distinguished Lecturer in Polymer Science and Engineering , Sichuan University 2017 Blavatnik Young Scientist Award Finalist Protocol Activity...developing the basic polymer chemistry of responsive, biopolymer/polymer hybrid materials. This began with us generating a nobornyl-PNA (peptide

  3. Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

    Directory of Open Access Journals (Sweden)

    Ruth Pye

    2018-02-01

    Full Text Available Devil facial tumor disease (DFTD is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33, these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol® and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of

  4. Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release

    Science.gov (United States)

    Pye, Ruth; Patchett, Amanda; McLennan, Elspeth; Thomson, Russell; Carver, Scott; Fox, Samantha; Pemberton, David; Kreiss, Alexandre; Baz Morelli, Adriana; Silva, Anabel; Pearse, Martin J.; Corcoran, Lynn M.; Belov, Katherine; Hogg, Carolyn J.; Woods, Gregory M; Lyons, A. Bruce

    2018-01-01

    Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government’s Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti

  5. Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder

    Science.gov (United States)

    Amare, Azmeraw T.; Schubert, Klaus Oliver; Tekola-Ayele, Fasil; Hsu, Yi-Hsiang; Sangkuhl, Katrin; Jenkins, Gregory; Whaley, Ryan M.; Barman, Poulami; Batzler, Anthony; Altman, Russ B.; Arolt, Volker; Brockmöller, Jürgen; Chen, Chia-Hui; Domschke, Katharina; Hall-Flavin, Daniel K.; Hong, Chen-Jee; Illi, Ari; Ji, Yuan; Kampman, Olli; Kinoshita, Toshihiko; Leinonen, Esa; Liou, Ying-Jay; Mushiroda, Taisei; Nonen, Shinpei; Skime, Michelle K.; Wang, Liewei; Kato, Masaki; Liu, Yu-Li; Praphanphoj, Verayuth; Stingl, Julia C.; Bobo, William V.; Tsai, Shih-Jen; Kubo, Michiaki; Klein, Teri E.; Weinshilboum, Richard M.; Biernacka, Joanna M.; Baune, Bernhard T.

    2018-01-01

    Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs. PMID:29559929

  6. Physiological and molecular responses to drought in Petunia: the importance of stress severity

    Science.gov (United States)

    Kim, Jongyun

    2012-01-01

    Plant responses to drought stress vary depending on the severity of stress and the stage of drought progression. To improve the understanding of such responses, the leaf physiology, abscisic acid (ABA) concentration, and expression of genes associated with ABA metabolism and signalling were investigated in Petunia × hybrida. Plants were exposed to different specific substrate water contents (θ = 0.10, 0.20, 0.30, or 0.40 m3·m–3) to induce varying levels of drought stress. Plant responses were investigated both during the drying period (θ decreased to the θ thresholds) and while those threshold θ were maintained. Stomatal conductance (gs) and net photosynthesis (A) decreased with decreasing midday leaf water potential (Ψleaf). Leaf ABA concentration increased with decreasing midday Ψleaf and was negatively correlated with gs (r = –0.92). Despite the increase in leaf ABA concentration under drought, no significant effects on the expression of ABA biosynthesis genes were observed. However, the ABA catabolism-related gene CYP707A2 was downregulated, primarily in plants under severe drought (θ = 0.10 m3∙m–3), suggesting a decrease in ABA catabolism under severe drought. Expression of phospholipase Dα (PLDα), involved in regulating stomatal responses to ABA, was enhanced under drought during the drying phase, but there was no relationship between PLDα expression and midday Ψleaf after the θ thresholds had been reached. The results show that drought response of plants depends on the severity of drought stress and the phase of drought progression. PMID:23077204

  7. 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.

  8. Major Links.

    Science.gov (United States)

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  9. Major Roads

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  10. A molecular mechanism for the origin of a key evolutionary innovation, the bird beak and palate, revealed by an integrative approach to major transitions in vertebrate history.

    Science.gov (United States)

    Bhullar, Bhart-Anjan S; Morris, Zachary S; Sefton, Elizabeth M; Tok, Atalay; Tokita, Masayoshi; Namkoong, Bumjin; Camacho, Jasmin; Burnham, David A; Abzhanov, Arhat

    2015-07-01

    The avian beak is a key evolutionary innovation whose flexibility has permitted birds to diversify into a range of disparate ecological niches. We approached the problem of the mechanism behind this innovation using an approach bridging paleontology, comparative anatomy, and experimental developmental biology. First, we used fossil and extant data to show the beak is distinctive in consisting of fused premaxillae that are geometrically distinct from those of ancestral archosaurs. To elucidate underlying developmental mechanisms, we examined candidate gene expression domains in the embryonic face: the earlier frontonasal ectodermal zone (FEZ) and the later midfacial WNT-responsive region, in birds and several reptiles. This permitted the identification of an autapomorphic median gene expression region in Aves. To test the mechanism, we used inhibitors of both pathways to replicate in chicken the ancestral amniote expression. Altering the FEZ altered later WNT responsiveness to the ancestral pattern. Skeletal phenotypes from both types of experiments had premaxillae that clustered geometrically with ancestral fossil forms instead of beaked birds. The palatal region was also altered to a more ancestral phenotype. This is consistent with the fossil record and with the tight functional association of avian premaxillae and palate in forming a kinetic beak. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  11. Molecular and biochemical responses in the midgut of the silkworm, Bombyx mori, infected with Nosema bombycis.

    Science.gov (United States)

    Li, Zhi; Wang, Yu; Wang, Linling; Zhou, Zeyang

    2018-03-06

    Microsporidia are a group of eukaryotic intracellular parasites that infect almost all vertebrates and invertebrates. However, there is little information available of how microsporidia obtain nutrients and energy from host cells. The purpose of this study was to investigate the energy and material requirements of Nosema bombycis for the invasion procedure through analyzing the global variation of the gene expression, protein abundance, fatty acids level and ATP flux induced by the microsporidia N. bombycis infection in the midgut of the silkworm Bombyx mori. A suppression subtractive hybridization (SSH) and quantitative real-time PCR (qPCR) analysis were performed to identify the genes upregulated in the midgut of B. mori 48 h following N. bombycis infection. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to annotate and summarize the differentially expressed genes, according to the categories 'molecular function', 'cellular component' and 'biological process'. To evaluate the nutrition material and energy costs in B.mori infected by N. bombycis, biochemical analysis was performed to determine the variation of protein abundance, fatty acid levels and ATP flux with or without the microsporidia N. bombycis infection in the midgut of the silkworm B. mori. A total of 744 clones were obtained, 288 clones were randomly selected for sequencing, and 110 unigenes were generated. Amongst these, 49.21%, 30.16% and 14.29% genes were involved in 19 molecular functions, 19 biological processes and nine cellular components, respectively. A total of 11 oxidative phosphorylation- and eight proton-coupled ATP synthesis-related genes were upregulated. Seven protein degradation-, three fat degradation-related genes were upregulated, and no genes related to the de novo synthesis of amino acids and fatty acids were significantly upregulated. The data from the biochemical analysis showed the contents of total protein and ATP of B. mori

  12. Prospective Molecular Profiling of Melanoma Metastases Suggests Classifiers of Immune Responsiveness

    Science.gov (United States)

    Wang, Ena; Miller, Lance D.; Ohnmacht, Galen A.; Mocellin, Simone; Perez-Diez, Ainhoa; Petersen, David; Zhao, Yingdong; Simon, Richard; Powell, John I.; Asaki, Esther; Alexander, H. Richard; Duray, Paul H.; Herlyn, Meenhard; Restifo, Nicholas P.; Liu, Edison T.; Rosenberg, Steven A.; Marincola, Francesco M.

    2008-01-01

    We amplified RNAs from 63 fine needle aspiration (FNA) samples from 37 s.c. melanoma metastases from 25 patients undergoing immunotherapy for hybridization to a 6108-gene human cDNA chip. By prospectively following the history of the lesions, we could correlate transcript patterns with clinical outcome. Cluster analysis revealed a tight relationship among autologous synchronously sampled tumors compared with unrelated lesions (average Pearson's r = 0.83 and 0.7, respectively, P < 0.0003). As reported previously, two subgroups of metastatic melanoma lesions were identified that, however, had no predictive correlation with clinical outcome. Ranking of gene expression data from pretreatment samples identified ∼30 genes predictive of clinical response (P < 0.001). Analysis of their annotations denoted that approximately half of them were related to T-cell regulation, suggesting that immune responsiveness might be predetermined by a tumor microenvironment conducive to immune recognition. PMID:12097256

  13. Molecular dynamics simulation of the response of bi-disperse polyelectrolyte brushes to external electric fields

    International Nuclear Information System (INIS)

    Zhang Fen; Ding Huan-Da; Duan Chao; Tong Chao-Hui; Zhao Shuang-Liang

    2017-01-01

    Langevin dynamics simulations have been performed to investigate the response of bi-disperse and strong polyacid chains grafted on an electrode to electric fields generated by opposite surface charges on the polyelectrolyte (PE)-grafted electrode and a second parallel electrode. Simulation results clearly show that, under a negative external electric field, the longer grafted PE chains are more strongly stretched than the shorter ones in terms of the relative change in their respective brush heights. Whereas under a positive external electric field, the grafted shorter chains collapse more significantly than the longer ones. It was found that, under a positive external electric field, the magnitude of the total electric force acting on one shorter PE chain is larger than that on one longer PE chain, or vice versa. The effects of smeared and discrete charge distributions of grafted PE chains on the response of PE brushes to external electric fields were also examined. (paper)

  14. Molecular characterization of the submergence response of Arabidopsis thaliana ecotype Columbia

    DEFF Research Database (Denmark)

    Lee, S.C.; Mustroph, A.; Sasidaharan, R.

    2011-01-01

    partial pressure of the petiole and root had stabilized at c. 6 and 0.1 kPa, respectively. As controls, plants were untreated or exposed to darkness. Following quantitative profiling of cellular mRNAs with the Affymetrix ATH1 platform, changes in the transcriptome in response to submergence, early...... darkness, and O2-deprivation were evaluated by fuzzy k-means clustering. This identified genes co-regulated at the conditional, developmental or organ-specific level. Mutants for 10 differentially expressed HYPOXIA-RESPONSIVE UNKNOWN PROTEIN (HUP) genes were screened for altered submergence tolerance....... • The analysis identified 34 genes that were ubiquitously co-regulated by submergence and O2 deprivation. The biological functions of these include signaling, transcription, and anaerobic energy metabolism. HUPs comprised 40% of the co-regulated transcripts and mutants of seven of these genes were significantly...

  15. The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking and stress response.

    Science.gov (United States)

    Wang, Xing; Zhang, Ji-long; Feng, Xiu-xiu; Li, Hong-jie; Zhang, Gen-fa

    2017-04-20

    Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO 2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking, transcriptional and post-translational regulations, and abiotic stress responses. Moreover, we also discuss the current research trends and future directions on PIPs.

  16. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  17. Enhancement of human adaptive immune responses by administrati