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Sample records for major molecular responses

  1. The significance of early, major and stable molecular responses in chronic myeloid leukemia in the imatinib era.

    PubMed

    Breccia, Massimo; Alimena, Giuliana

    2011-08-01

    Tyrosine kinase inhibitors (TKI) have dramatically changed the management and the outcome of chronic myeloid leukemia (CML) patients. Imatinib is recognized as gold standard first-line therapy and impressive clinical and cytogenetic responses are obtained in the majority of chronic phase patients treated with this drug. Quantitative polymerase chain reaction (RQ-PCR) tool is used to monitor molecular residual disease, but practical issues are associated to measurement of molecular responses. Several evidences have now proved that molecular responses have prognostic significance: patients who achieve early molecular response are more likely to obtain durable cytogenetic response and to present less rate of disease progression. While some reports indicated that achieving major molecular response (MMR) represents the most important endpoint associated to best outcome, some other reports indicated that achievement of MMR does not improve the greatest clinical benefit brought by complete cytogenetic response. In this review, we discuss on the role of molecular monitoring, the significance of early response and its correlation with outcome, the significance of major and complete molecular response, the emphasized value of a stable molecular response, the early identification of resistance presenting with increased molecular level.

  2. Delayed cytogenetic and major molecular responses associated to increased BMI at baseline in chronic myeloid leukemia patients treated with imatinib.

    PubMed

    Breccia, Massimo; Loglisci, Giuseppina; Salaroli, Adriano; Serrao, Alessandra; Mancini, Marco; Diverio, Daniela; Latagliata, Roberto; Alimena, Giuliana

    2013-06-01

    Obesity, measured as body mass index (BMI), has been identified as a possible risk factor for several solid tumors as well as for chronic myeloid leukemia (CML). To date, no correlations have been reported in this latter disease between BMI at baseline and response to targeted therapies. We refer here on the impact of BMI on clinical response in 339 chronic phase (CP) CML patients treated with imatinib and 35 CP-CML patients treated frontline with nilotinib. If compared to patients with low BMI (<18.5-25), patients with increased BMI (>25-40) at diagnosis who received imatinib showed a significantly longer median time to achieve complete cytogenetic response (6.8 months vs 3.3 months, p=0.001), a reduced rate of major molecular response (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.01). Conversely, no differences were revealed with respect to BMI in patients treated frontline with nilotinib and also patients with increased BMI obtained rapidly CCyR and MMR with an incidence similar to that of underweight/normal weight patients. These results suggest that CML patients with increased weight at baseline should be followed and carefully monitored if treated with standard dose imatinib frontline for a possible early switch.

  3. Molecular and Immunological Significance of Chimpanzee Major Histocompatibility Complex Haplotypes for Hepatitis C Virus Immune Response and Vaccination Studies

    PubMed Central

    Mizukoshi, Eishiro; Nascimbeni, Michelina; Blaustein, Joshua B.; Mihalik, Kathleen; Rice, Charles M.; Liang, T. Jake; Feinstone, Stephen M.; Rehermann, Barbara

    2002-01-01

    The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes. PMID:12021342

  4. A Single Nucleotide Polymorphism in cBIM Is Associated with a Slower Achievement of Major Molecular Response in Chronic Myeloid Leukaemia Treated with Imatinib

    PubMed Central

    Augis, Vanessa; Airiau, Kelly; Josselin, Marina; Turcq, Béatrice; Mahon, François-Xavier; Belloc, Francis

    2013-01-01

    Purpose 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. Experimental Design 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. Results 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 (p<0.001) and the presence of the T allele significantly lengthened the time to achieve a major molecular response (MMR). Finally, the presence of the T allele was related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy controls. Conclusion These results suggest that the analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients. PMID:24223824

  5. Molecular and biological interaction between major histocompatibility complex class I antigens and luteinizing hormone receptors or beta-adrenergic receptors triggers cellular response in mice.

    PubMed Central

    Solano, A R; Cremaschi, G; Sánchez, M L; Borda, E; Sterin-Borda, L; Podestá, E J

    1988-01-01

    Purified IgG from BALB/c mouse anti-C3H serum exerts positive inotropic and chronotropic effects in C3H mouse atria and induces testosterone synthesis in C3H mouse Leydig cells. The effect depends on IgG concentration and can be abolished by beta-adrenergic-receptor and luteinizing hormone-receptor antagonists. IgG interferes with the binding of dihydroalprenolol and luteinizing hormone. Monoclonal antibodies against major histocompatibility complex class I antigens were active on the Leydig cells of C3H and BALB/c mice. There was a parallelism between the effect of each individual monoclonal antibody with specificity for a particular haplotype and the response of the target cell from the strains carrying such haplotypes. These antibodies could precipitate the soluble luteinizing hormone-receptor complex. The results suggested that bound hormone triggers the association of major histocompatibility class I antigen with the receptor, thereby activating the respective target cells. PMID:2839829

  6. A Response to "BIO 2010: Transforming Undergraduate Education for Future Research Biologists," from the Perspective of the Biochemistry and Molecular Biology Major Program at Kenyon College

    ERIC Educational Resources Information Center

    Slonczewski, Joan L.; Marusak, Rosemary

    2004-01-01

    The National Research Council completed a major study of undergraduate biology education, "BIO 2010-Transforming Undergraduate Education For Future Research Biologists (BIO 2010)," funded by the Howard Hughes Medical Institute and the National Institutes of Health. The "BIO 2010" report recommends that biology pedagogy should use an…

  7. Hypoxia: from molecular responses to ecosystem responses.

    PubMed

    Wu, Rudolf S S

    2002-01-01

    Hypoxia affects thousands of km2 of marine waters all over the world, and has caused mass mortality of marine animals, benthic defaunation and decline in fisheries production in many places. The severity, frequency occurrence and spatial scale of hypoxia have increased in the last few decades. Due to rapid human population growth and global warming, the problem of hypoxia is likely to become worse in the coming years. Molecular responses of marine animals to hypoxia are poorly known. In many animals, a haem protein probably serves as the cellular sensor for oxygen, and reactive oxygen species are generated as signaling molecules. In mammal and fish, a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF-1) has been identified. HIF-1 receives signals from the molecular oxygen senor through redox reactions and/or phosphorylation, and in turn, regulates the transcription of a number of hypoxia-inducible genes, including genes involved in erythropoiesis, angiogenesis and glycolysis. These molecular responses then cascade into a series of biochemical and physiological adjustments, enabling the animal to survive better under hypoxic conditions. Marine animals respond to hypoxia by first attempting to maintain oxygen delivery (e.g. increases in respiration rate, number of red blood cells, or oxygen binding capacity of hemoglobin), then by conserving energy (e.g. metabolic depression, down regulation of protein synthesis and down regulation/modification of certain regulatory enzymes). Upon exposure to prolonged hypoxia, animals must eventually resort to anaerobic respiration. Hypoxia reduces growth and feeding, which may eventually affect individual fitness. Effects of hypoxia on reproduction and development of marine animals, albeit important in affecting species survival, remain almost unknown. Many fish and marine organisms can detect, and actively avoid hypoxia. Some benthos may leave their burrows and move to sediment surface during hypoxia. These

  8. Contraction of online response to major events.

    PubMed

    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. PMID:24586499

  9. Contraction of Online Response to Major Events

    PubMed Central

    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. PMID:24586499

  10. Contraction of online response to major events.

    PubMed

    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.

  11. Molecular biology of major components of chloride cells.

    PubMed

    Hirose, Shigehisa; Kaneko, Toyoji; Naito, Nobuko; Takei, Yoshio

    2003-12-01

    Current understanding of chloride cells (CCs) is briefly reviewed with emphasis on molecular aspects of their channels, transporters and regulators. Seawater-type and freshwater-type CCs have been identified based on their shape, location and response to different ionic conditions. Among the freshwater-type CCs, subpopulations are emerging that are implicated in the uptake of Na(+), Cl(-) and Ca(2+), respectively, and can be distinguished by their shape of apical crypt and affinity for lectins. The major function of the seawater CC is transcellular secretion of Cl(-), which is accomplished by four major channels and transporters: (1). CFTR Cl(-) channel, (2). Na(+),K(+)-ATPase, (3). Na(+)/K(+)/2Cl(-) cotransporter and (4). a K(+) channel. The first three components have been cloned and characterized, but concerning the K(+) channel that is essential for the continued generation of the driving force by Na(+),K(+)-ATPase, only one candidate is identified. Although controversial, freshwater CCs seem to perform the uptake of Na(+), Cl(-) and Ca(2+) in a manner analogous to but slightly different from that seen in the absorptive epithelia of mammalian kidney and intestine since freshwater CCs face larger concentration gradients than ordinary epithelial cells. The components involved in these processes are beginning to be cloned, but their CC localization remains to be established definitively. The most important yet controversial issue is the mechanism of Na(+) uptake. Two models have been postulated: (i). the original one involves amiloride-sensitive electroneutral Na(+)/H(+) exchanger (NHE) with the driving force generated by Na(+),K(+)-ATPase and carbonic anhydrase (CA) and (ii). the current model suggests that Na(+) uptake occurs through an amiloride-sensitive epithelial sodium channel (ENaC) electrogenically coupled to H(+)-ATPase. While fish ENaC remains to be identified by molecular cloning and database mining, fish NHE has been cloned and shown to be highly

  12. An altered peripheral IL6 response in major depressive disorder.

    PubMed

    Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

    2016-05-01

    Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in

  13. Major Molecular Response Achievement in CML Patients Can Be Predicted by BCR-ABL1/ABL1 or BCR-ABL1/GUS Ratio at an Earlier Time Point of Follow-Up than Currently Recommended

    PubMed Central

    Huet, Sarah; Cony-Makhoul, Pascale; Heiblig, Maël; Tigaud, Isabelle; Gazzo, Sophie; Belhabri, Amine; Souche, Denis; Michallet, Mauricette; Magaud, Jean-Pierre; Hayette, Sandrine; Nicolini, Franck

    2014-01-01

    Recent studies demonstrate that early molecular response to tyrosine-kinase inhibitors is strongly predictive of outcome in chronic myeloid leukemia patients and that early response landmarks may identify patients at higher risk for transformation who would benefit from an early switch to second-line therapy. In this study, we evaluated the ability of the control gene GUS to identify relevant thresholds for known therapeutic decision levels (BCR-ABL1/ABL1IS  = 10% and 0.1%). We then defined the most relevant cut-offs for early molecular response markers (transcript level at 3 months, halving time and log reduction between diagnosis and 3 months of treatment) using GUS or ABL1. We demonstrated that, although both control genes could be used (in an equivalent way) to accurately assess early molecular response, the BCR-ABL1/GUS level at diagnosis is impacted by the higher GUS copy number over-expressed in CML cells, thus negatively impacting its ability to completely replace ABL1 at diagnosis. Furthermore, we pointed out, for the first time, that it would be helpful to monitor BCR-ABL1 levels at an earlier time point than that currently performed, in order to assess response to first-line tyrosine-kinase inhibitors and consider a potential switch of therapy as early as possible. We evaluated this optimal time point as being 19 days after the start of treatment in our cohort. PMID:25203717

  14. Molecular and genetic inflammation networks in major human diseases.

    PubMed

    Zhao, Yongzhong; Forst, Christian V; Sayegh, Camil E; Wang, I-Ming; Yang, Xia; Zhang, Bin

    2016-07-19

    It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured the most critical inflammation-involved molecules, genetic susceptibilities, epigenetic factors, and environmental factors, our schemata on the role of inflammation in complex diseases remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the molecular and genetic inflammation networks underlying major human diseases. In this review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer's disease, Parkinson's disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2 immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic

  15. Molecular, Functional, and Structural Imaging of Major Depressive Disorder.

    PubMed

    Zhang, Kai; Zhu, Yunqi; Zhu, Yuankai; Wu, Shuang; Liu, Hao; Zhang, Wei; Xu, Caiyun; Zhang, Hong; Hayashi, Takuya; Tian, Mei

    2016-06-01

    Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD. PMID:27142698

  16. Molecular cues guiding inflammatory responses.

    PubMed

    Barreiro, Olga; Martín, Pilar; González-Amaro, Roberto; Sánchez-Madrid, Francisco

    2010-05-01

    Alarm signals generated at inflammatory foci reach the vascular lumen to attract immune cells towards the affected tissue. Different leucocyte subsets decipher and integrate these complex signals in order to make adequate decisions for their migration towards the inflamed tissue. Soluble cues (cytokines and chemokines) and membrane receptors in both endothelium and leucocytes orchestrate the coordinated recruitment of specific inflammatory cell subsets. All these molecules are spatio-temporally organized in specialized structures at the luminal side of endothelium and the leucocyte membrane or are generated as chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and their receptors as well as adhesion molecules expressed by each leucocyte subset determine their recruitment for participation in specific inflammatory pathologies. Whenever inflammatory signals are altered or misprocessed, inflammation can become chronic, causing extensive tissue damage. To combat chronic inflammation and autoimmune diseases, novel therapeutic strategies attempt to silence the predominant signals in each inflammatory scenario. In this review, we provide a general overview of all these aspects related to the molecular regulation of leucocyte guidance in inflammatory responses.

  17. Education and Training for Major Incidents Through Medical Response to Major Incidents-MRMI course.

    PubMed

    Samardzic, Josip; Hreckovski, Boris; Hasukic, Ismar

    2015-06-01

    Incidence of major incidents nowadays is in constant growth, especially in last decade. Main goal of all health systems is to minimize and prevent tragic outcomes of major incidents, thus reducing morbidity and mortality and psychological and physical suffering. Lessons learned from Major Incidents throughout the World point out that tragical outcomes could be avoided through adequate preparation and planning. Necessity to plan and to educate to response to Major incident is greater than ever. Finally it is legal obligation that every hospital has plan in case of Major Incident. Effective planning must incorporate: identification of risks, methods of prevention, identification of all recourses, anticipation of errors and detailed protocol of response for each participant. Knowledge and skills needed for Major incident situations must be adopted through interactive training and practical exercise ("learning by doing"). That can be achieved by field exercises and by simulation model. Simulation model has many advantages and enables simultaneous education and training of all participants; scene, transport, hospitals, communication and command which than can be evaluated through objective outcomes. The goal is to train medical staff in real time, on position they are assigned to, with available resources in conditions of Major incident.

  18. Education and Training for Major Incidents Through Medical Response to Major Incidents–MRMI course

    PubMed Central

    Samardzic, Josip; Hreckovski, Boris; Hasukic, Ismar

    2015-01-01

    Incidence of major incidents nowadays is in constant growth, especially in last decade. Main goal of all health systems is to minimize and prevent tragic outcomes of major incidents, thus reducing morbidity and mortality and psychological and physical suffering. Lessons learned from Major Incidents throughout the World point out that tragical outcomes could be avoided through adequate preparation and planning. Necessity to plan and to educate to response to Major incident is greater than ever. Finally it is legal obligation that every hospital has plan in case of Major Incident. Effective planning must incorporate: identification of risks, methods of prevention, identification of all recourses, anticipation of errors and detailed protocol of response for each participant. Knowledge and skills needed for Major incident situations must be adopted through interactive training and practical exercise („learning by doing„). That can be achieved by field exercises and by simulation model. Simulation model has many advantages and enables simultaneous education and training of all participants; scene, transport, hospitals, communication and command which than can be evaluated through objective outcomes. The goal is to train medical staff in real time, on position they are assigned to, with available resources in conditions of Major incident. PMID:26236085

  19. The Biochemistry and Molecular Biology Major and Liberal Education

    ERIC Educational Resources Information Center

    Liberal Education, 2009

    2009-01-01

    The defining task for undergraduate departments is the design of a major, including the number and content of courses as well as other requirements. Department members must weigh the desire to produce graduates superbly prepared for further study against the charge that the major requires too large a share of an undergraduate's course options.…

  20. Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors

    PubMed Central

    Garbett, K A; Vereczkei, A; Kálmán, S; Wang, L; Korade, Ž; Shelton, R C; Mirnics, K

    2015-01-01

    Major depressive disorder (MDD) is increasingly viewed as interplay of environmental stressors and genetic predisposition, and recent data suggest that the disease affects not only the brain, but the entire body. As a result, we aimed at determining whether patients with major depression have aberrant molecular responses to stress in peripheral tissues. We examined the effects of two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD and matched healthy controls (CNTR). Our results demonstrate that both MDD and CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most importantly, a significant part (messenger RNAs (mRNAs): 26–33% microRNAs (miRNAs): 81–90%) of the molecular response was only observed in MDD, but not in CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA signatures, identifying responses to each stressor characteristic for the MDD fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an aberrant engagement of molecular pathways, such as apoptosis, regulation of cell cycle, cell migration, metabolic control and energy production. In conclusion, the metabolic challenges evoked by GAL or RL in dermal fibroblasts exposed adaptive dysfunctions on mRNA and miRNA levels that are characteristic for MDD. This finding underscores the need to challenge biological systems to bring out disease-specific deficits, which otherwise might remain hidden under resting conditions. PMID:25756806

  1. Molecular Aspects of Bone Resorption in β-Thalassemia Major

    PubMed Central

    Saki, Najmaldin; Abroun, Saeid; Salari, Fatemeh; Rahim, Fakher; Shahjahani, Mohammad; Javad, Mohammadi-Asl

    2015-01-01

    β-thalassemia is the most common single gene disorder worldwide, in which hemoglobin β-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes. PMID:26199898

  2. Genetic susceptibility for bipolar disorder and response to antidepressants in major depressive disorder.

    PubMed

    Tansey, Katherine E; Guipponi, Michel; Domenici, Enrico; Lewis, Glyn; Malafosse, Alain; O'Donovan, Michael; Wendland, Jens R; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2014-01-01

    The high heterogeneity of response to antidepressant treatment in major depressive disorder (MDD) makes individual treatment outcomes currently unpredictable. It has been suggested that resistance to antidepressant treatment might be due to undiagnosed bipolar disorder or bipolar spectrum features. Here, we investigate the relationship between genetic susceptibility for bipolar disorder and response to treatment with antidepressants in MDD. Polygenic scores indexing risk for bipolar disorder were derived from the Psychiatric Genomics Consortium Bipolar Disorder whole genome association study. Linear regressions tested the effect of polygenic risk scores for bipolar disorder on proportional reduction in depression severity in two large samples of individuals with MDD, treated with antidepressants, NEWMEDS (n=1,791) and STAR*D (n=1,107). There was no significant association between polygenic scores for bipolar disorder and response to treatment with antidepressants. Our data indicate that molecular measure of genetic susceptibility to bipolar disorder does not aid in understanding non-response to antidepressants.

  3. The cortisol awakening response and major depression: examining the evidence

    PubMed Central

    Dedovic, Katarina; Ngiam, Janice

    2015-01-01

    A vast body of literature has revealed that dysregulation of the hypothalamic–pituitary–adrenal (HPA) stress axis is associated with etiology of major depressive disorder (MDD). There are many ways that the dysregulation of the HPA axis can be assessed: by sampling diurnal basal secretion and/or in response to a stress task, pharmacological challenge, and awakening. Here, we focus on the association between cortisol awakening response (CAR), as one index of HPA axis function, and MDD, given that the nature of this association is particularly unclear. Indeed, in the following selective review, we attempt to reconcile sometimes-divergent evidence of the role of CAR in the pathway to depression. We first examine association of CAR with psychological factors that have been linked with increased vulnerability to develop depression. Then, we summarize the findings regarding the CAR profile in those with current depression, and evaluate evidence for the role of CAR following depression resolution and continued vulnerability. Finally, we showcase longitudinal studies showing the role of CAR in predicting depression onset and recurrence. Overall, the studies reveal an important, but complex, association between CAR and vulnerability to depression. PMID:25999722

  4. Major accidents and disaster response: The Swiss perspective

    SciTech Connect

    Favre, R.

    1995-12-31

    The coordination of the emergency preparedness towards disasters and major accidents takes place into the context of a global security policy. The purpose of this policy is to guarantee the survival of the population and to protect vital installations within a given area (state, region, canton, district, prefecture). According to the Swiss law--except in the case of a nuclear accident--the authorities of the cantons and communes are in charge of disaster relief in their jurisdiction. In addition, various instruments subordinated to Federal Departments (i.e., ministries) can be required either to function as experts or--on request and while respecting the principle of subsidiarity--to contribute to disaster response. Also in peace-time, parts of the army (rescue troops, engineers, medical units, ...) or parts of the means of the civil defense may be involved. In accordance with Switzerland`s federal state organization, each canton has worked out its own structure for disaster response (examples are provided in the paper). Although each of them has its own peculiarities and the available means can vary, several local events in the past few years have allowed them to give proof of their efficiency.

  5. Electroconvulsive therapy exerts mainly acute molecular changes in serum of major depressive disorder patients.

    PubMed

    Stelzhammer, Viktoria; Guest, Paul C; Rothermundt, Matthias; Sondermann, Carina; Michael, Nikolaus; Schwarz, Emanuel; Rahmoune, Hassan; Bahn, Sabine

    2013-10-01

    Electroconvulsive therapy (ECT) is mainly used to treat medication resistant major depressive disorder (MDD) patients, with a remission rate of up to 90%. However, little is known about the serum molecular changes induced by this treatment. Understanding the mechanisms of action of ECT at the molecular level could lead to identification of response markers and potential new drug targets for more effective antidepressant treatments. We have carried out a pilot study which analysed serum samples of MDD patients who received a series of ECT treatments over 4 weeks. Patients received only ECT treatments over the first two weeks and a combination of ECT and antidepressant drugs (AD) over the subsequent two weeks. Blood serum analyses were carried out using a combination of multiplex Human MAP® immunoassay and liquid-chromatography mass spectrometry (LC-MS(E)) profiling. This showed that ECT had a predominant acute effect on the levels of serum proteins and small molecules, with changes at the beginning of ECT treatment and after administration of the ECT+AD combination treatment. This suggested a positive interaction between the two types of treatment. Changed molecules included BDNF, CD40L, IL-8, IL-13, EGF, IGF-1, pancreatic polypeptide, SCF, sortilin-1 and others which have already been implicated in MDD pathophysiology. We conclude that ECT appears to exert mainly acute effects on serum molecules.

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed Central

    dos Reis, Sávio Pinho; Lima, Aline Medeiros; de Souza, Cláudia Regina Batista

    2012-01-01

    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. PMID:22942725

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

    NASA Astrophysics Data System (ADS)

    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

  9. Molecular modeling of responsive polymer films

    SciTech Connect

    Tagliazucchi, Mario; Calvo, Ernesto J; Szleifer, Igal

    2010-06-29

    In this perspective, we have shown three different cases of responsive polymers at surfaces where the properties of the surface can be varied in response to cues from the bulk solution or in the presence of an external field. The most important conclusion in all three cases is that the chemical reaction equilibrium, physical interactions and molecular organization are strongly coupled, and it is imperative to consider the global and local changes that occur to the surface structure and properties due to this coupling. In particular acid-base and redox equilibrium are very different in polymer-modified surfaces than in the corresponding bulk solutions. Moreover, the definition of ‘‘apparent redox potentials’’ and ‘‘apparent pKa’’results from the averaging over highly inhomogeneous values,and, therefore, they do not necessarily represent the state of the layer and the local values and their variation are very important for the design of functional surfaces. The very large variation on chemical equilibrium results from the optimization of all the interactions. The picture that emerges is that trying to deduce what the final state of the system is by looking at the individual optimization of each contribution leads to qualitative incorrect assumptions and only the minimization of the complete free energy leads to the proper behavior in these complex systems.In the cases where domain formation is possible in grafted weak polyacid layers charge regulation may lead to regimes of coexistence between aggregates with relatively low fraction of charged polymer segments surrounded by highly stretched chains that have a relatively high fraction of charged groups.Therefore, one can control the state of charge, local electrostatic potential and local pH in all three dimensions with im-portant gradients on length scales of nanometers. For hydrophobic redox polymers we show how the application of an electrode potential can lead to changes in the structure

  10. Foundational concepts and underlying theories for majors in "biochemistry and molecular biology".

    PubMed

    Tansey, John T; Baird, Teaster; 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) foundational skills that undergraduate majors in biochemistry and molecular biology must understand to complete their major coursework. Using information gained from these workshops, as well as from the ASBMB accreditation working group and the NSF Vision and Change report, the Core Concepts working group has developed a consensus list of learning outcomes and objectives based on five foundational concepts (evolution, matter and energy transformation, homeostasis, information flow, and macromolecular structure and function) that represent the expected conceptual knowledge base for undergraduate degrees in biochemistry and molecular biology. This consensus will aid biochemistry and molecular biology educators in the development of assessment tools for the new ASBMB recommended curriculum.

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

    PubMed

    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.

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

    ERIC Educational Resources Information Center

    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…

  13. Major gene is responsible for anencephaly among Iranian Jews

    SciTech Connect

    Zlotogora, J.

    1995-03-13

    Anencephaly is relatively frequent in Jews originating from Iran, in particular when its incidence is compared to that of open spina bifida in the same population (12 cases of anencephaly out of 14 cases of neural tube defects). The high incidence of this disorder in Iranian Jews, a relatively isolated community with a very high rate of consanguinity, suggests that anencephaly is caused by a major recessive gene. This possibility is supported by the sex ratio among these patients, which was significantly different from that observed for patients with anencephaly in other populations. 10 refs.

  14. Major Radiations in the Evolution of Caviid Rodents: Reconciling Fossils, Ghost Lineages, and Relaxed Molecular Clocks

    PubMed Central

    Pérez, María Encarnación; Pol, Diego

    2012-01-01

    Background Caviidae is a diverse group of caviomorph rodents that is broadly distributed in South America and is divided into three highly divergent extant lineages: Caviinae (cavies), Dolichotinae (maras), and Hydrochoerinae (capybaras). The fossil record of Caviidae is only abundant and diverse since the late Miocene. Caviids belongs to Cavioidea sensu stricto (Cavioidea s.s.) that also includes a diverse assemblage of extinct taxa recorded from the late Oligocene to the middle Miocene of South America (“eocardiids”). Results A phylogenetic analysis combining morphological and molecular data is presented here, evaluating the time of diversification of selected nodes based on the calibration of phylogenetic trees with fossil taxa and the use of relaxed molecular clocks. This analysis reveals three major phases of diversification in the evolutionary history of Cavioidea s.s. The first two phases involve two successive radiations of extinct lineages that occurred during the late Oligocene and the early Miocene. The third phase consists of the diversification of Caviidae. The initial split of caviids is dated as middle Miocene by the fossil record. This date falls within the 95% higher probability distribution estimated by the relaxed Bayesian molecular clock, although the mean age estimate ages are 3.5 to 7 Myr older. The initial split of caviids is followed by an obscure period of poor fossil record (refered here as the Mayoan gap) and then by the appearance of highly differentiated modern lineages of caviids, which evidentially occurred at the late Miocene as indicated by both the fossil record and molecular clock estimates. Conclusions The integrated approach used here allowed us identifying the agreements and discrepancies of the fossil record and molecular clock estimates on the timing of the major events in cavioid evolution, revealing evolutionary patterns that would not have been possible to gather using only molecular or paleontological data alone. PMID

  15. National telemental health responses to a major bushfire disaster.

    PubMed

    Reifels, Lennart; Bassilios, Bridget; Pirkis, Jane

    2012-06-01

    In response to the Victorian bushfire disaster in 2009, various telemental health services were provided by three national agencies: Kids Helpline (BoysTown), MensLine Australia (Crisis Support Services) and Lifeline Australia. All provider agencies used their existing national service structures and staff resources, which were expanded to respond to bushfire-related service demand. We examined service provider reports and conducted key informant interviews. Despite a lack of quantitative data on consumer outcomes and perspectives, it appears that all three telemental health services experienced significant increases in overall service uptake levels in the wake of the bushfires. Uptake of specialized telephone-, web-, email- and crisis counselling services was substantial, although that of callback services was very limited. Potential clients encountered specific barriers in relation to service access and the callback model. The bushfire experience highlighted the impact of transitory living circumstances and the increased complexity of post-disaster calls on service provision. Telemental health services need to be integrated into mainstream services and disaster response structures.

  16. Molecular Response Theory in Terms of the Uncertainty Principle.

    PubMed

    Harde, Hermann; Grischkowsky, Daniel

    2015-08-27

    We investigate the time response of molecular transitions by observing the pulse reshaping of femtosecond THz-pulses propagating through polar vapors. By precisely modeling the pulse interaction with the molecular vapors, we derive detailed insight into this time response after an excitation. The measurements, which were performed by applying the powerful technique of THz time domain spectroscopy, are analyzed directly in the time domain or parallel in the frequency domain by Fourier transforming the pulses and comparing them with the molecular response theory. New analyses of the molecular response allow a generalized unification of the basic collision and line-shape theories of Lorentz, van Vleck-Weisskopf, and Debye described by molecular response theory. In addition, they show that the applied THz experimental setup allows the direct observation of the ultimate time response of molecules to an external applied electric field in the presence of molecular collisions. This response is limited by the uncertainty principle and is determined by the inverse spitting frequency between adjacent levels. At the same time, this response reflects the transition time of a rotational transition to switch from one molecular state to another or to form a coherent superposition of states oscillating with the splitting frequency. The presented investigations are also of fundamental importance for the description of the far-wing absorption of greenhouse gases like water vapor, carbon dioxide, or methane, which have a dominant influence on the radiative exchange in the far-infrared. PMID:26280761

  17. Molecular Response Theory in Terms of the Uncertainty Principle.

    PubMed

    Harde, Hermann; Grischkowsky, Daniel

    2015-08-27

    We investigate the time response of molecular transitions by observing the pulse reshaping of femtosecond THz-pulses propagating through polar vapors. By precisely modeling the pulse interaction with the molecular vapors, we derive detailed insight into this time response after an excitation. The measurements, which were performed by applying the powerful technique of THz time domain spectroscopy, are analyzed directly in the time domain or parallel in the frequency domain by Fourier transforming the pulses and comparing them with the molecular response theory. New analyses of the molecular response allow a generalized unification of the basic collision and line-shape theories of Lorentz, van Vleck-Weisskopf, and Debye described by molecular response theory. In addition, they show that the applied THz experimental setup allows the direct observation of the ultimate time response of molecules to an external applied electric field in the presence of molecular collisions. This response is limited by the uncertainty principle and is determined by the inverse spitting frequency between adjacent levels. At the same time, this response reflects the transition time of a rotational transition to switch from one molecular state to another or to form a coherent superposition of states oscillating with the splitting frequency. The presented investigations are also of fundamental importance for the description of the far-wing absorption of greenhouse gases like water vapor, carbon dioxide, or methane, which have a dominant influence on the radiative exchange in the far-infrared.

  18. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing

    PubMed Central

    Reid, Brian; Zhao, Min

    2014-01-01

    Significance: Natural, endogenous electric fields (EFs) and currents arise spontaneously after wounding of many tissues, especially epithelia, and are necessary for normal healing. This wound electrical activity is a long-lasting and regulated response. Enhancing or inhibiting this electrical activity increases or decreases wound healing, respectively. Cells that are responsible for wound closure such as corneal epithelial cells or skin keratinocytes migrate directionally in EFs of physiological magnitude. However, the mechanisms of how the wound electrical response is initiated and regulated remain unclear. Recent Advances: Wound EFs and currents appear to arise by ion channel up-regulation and redistribution, which are perhaps triggered by an intracellular calcium wave or cell depolarization. We discuss the possibility of stimulation of wound healing via pharmacological enhancement of the wound electric signal by stimulation of ion pumping. Critical Issues: Chronic wounds are a major problem in the elderly and diabetic patient. Any strategy to stimulate wound healing in these patients is desirable. Applying electrical stimulation directly is problematic, but pharmacological enhancement of the wound signal may be a promising strategy. Future Directions: Understanding the molecular regulation of wound electric signals may reveal some fundamental mechanisms in wound healing. Manipulating fluxes of ions and electric currents at wounds might offer new approaches to achieve better wound healing and to heal chronic wounds. PMID:24761358

  19. Molecular cloning, characterization, and expression of Cuc m 2, a major allergen in Cucumis melo

    PubMed Central

    Sankian, Mojtaba; Mahmoudi, Mahmoud; Varasteh, Abdol-Reza

    2013-01-01

    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. PMID:26989709

  20. [Major host-protective antigens of Taeniidae cestode and their molecular biological characteristics].

    PubMed

    Yue, Long; Fu, Bao-quan

    2014-12-01

    Taeniidae cestodes are the pathogens of cysticercosis and hydatid disease, these diseases lead to substantial economic losses in animal husbandry and cause morbidity and mortality in human population. In recent years, many host-protective antigens of Taeniidae cestodes has been found, and their recombinant protein vaccines have been developed against several species, such as Taenia ovis, T. saginata, T. solium, Echinococcus granulosus, and E. multilocularis. This paper focuses on the major host-protective antigens of Taeniidae cestodes and their molecular biological characteristics. PMID:25902683

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

    SciTech Connect

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

    2007-11-01

    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.

  2. Skin: major target organ of allergic reactions to small molecular weight compounds.

    PubMed

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

    2007-11-01

    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. Molecular mechanisms responsible for formation of Golgi ribbon.

    PubMed

    Mironov, Alexander A; Beznoussenko, Galina V

    2011-01-01

    The formation of the Golgi ribbon takes place in protists and metazoans. It is especially prominent in mammalian cells during interphase. Golgi ribbon formation represents an orchestrated sequence of events based not only on different molecular mechanisms but also on discrete cellular functions. Mechanisms responsible for the generation of the Golgi ribbon include Golgi centralization, cis- and trans-Golgins, molecular machines responsible for the fusion of cargo domains with cisternal rims, and several other less studied factors. Here, we substantiate the hypothesis that cis-Golgins function mostly not as tethering factors, but are responsible for the attachment of the cis-most cisternae to the medial Golgi stacks, whereas trans-Golgins are responsible for the attachment of the trans-most cisterna to the medial Golgi stacks. This hypothesis is tested analyzing predictions derived from it and related to molecular mechanisms responsible for mitotic fragmentation of Golgi stacks.

  4. Plant molecular stress responses face climate change.

    PubMed

    Ahuja, Ishita; de Vos, Ric C H; Bones, Atle M; Hall, Robert D

    2010-12-01

    Environmental stress factors such as drought, elevated temperature, salinity and rising CO₂ affect plant growth and pose a growing threat to sustainable agriculture. This has become a hot issue due to concerns about the effects of climate change on plant resources, biodiversity and global food security. Plant adaptation to stress involves key changes in the '-omic' architecture. Here, we present an overview of the physiological and molecular programs in stress adaptation focusing on how genes, proteins and metabolites change after individual and multiple environmental stresses. We address the role which '-omics' research, coupled to systems biology approaches, can play in future research on plants seemingly unable to adapt as well as those which can tolerate climatic change.

  5. Molecular Responses of the Spiral Ganglion to Aminoglycosides

    ERIC Educational Resources Information Center

    Balaban, Carey D.

    2005-01-01

    Aminoglycosides are toxic to both the inner ear hair cells and the ganglion cells that give rise to the eighth cranial nerve. According to recent studies, these cells have a repertoire of molecular responses to aminoglycoside exposure that engages multiple neuroprotective mechanisms. The responses appear to involve regulation of ionic homeostasis,…

  6. Molecular basis of major psychiatric diseases such as schizophrenia and depression.

    PubMed

    Tohyama, Masaya; Miyata, Shingo; Hattori, Tsuyoshi; Shimizu, Shoko; Matsuzaki, Shinsuke

    2015-06-01

    Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported. DISC1 is involved in neural development directly via adhesion molecules or via its binding partners of DISC1 such as elongation protein ζ-1 (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates neural development via stathmin 1 or via regulation of the DISC1-DBZ binding. Dysbindin is also involved in neural development by regulating centrosomal microtubule network formation. All such molecules examined to date are involved in neural development. Thus, these findings provide new molecular insights into the mechanisms of neural development and neuropsychiatric disorders. On the other hand, in addition to neurons, both DISC and DBZ have been detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 inhibits the differentiation of oligodendrocyte precursor cells into oligodendrocytes, while DBZ has a positive regulatory role in oligodendrocyte differentiation. Evidence suggesting that disturbance of oligodendrocyte development causes major depression is also described.

  7. Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder.

    PubMed

    Martins-de-Souza, Daniel

    2014-03-01

    Omics technologies emerged as complementary strategies to genomics in the attempt to understand human illnesses. In general, proteomics technologies emerged earlier than those of metabolomics for major depressive disorder (MDD) research, but both are driven by the identification of proteins and/or metabolites that can delineate a comprehensive characterization of MDD's molecular mechanisms, as well as lead to the identification of biomarker candidates of all types-prognosis, diagnosis, treatment, and patient stratification. Also, one can explore protein and metabolite interactomes in order to pinpoint additional molecules associated with the disease that had not been picked up initially. Here, results and methodological aspects of MDD research using proteomics, metabolomics, and protein interactomics are reviewed, focusing on human samples.

  8. A Glimpse to Background and Characteristics of Major Molecular Biological Networks

    PubMed Central

    Altaf-Ul-Amin, Md.; Katsuragi, Tetsuo; Sato, Tetsuo; Kanaya, Shigehiko

    2015-01-01

    Recently, biology has become a data intensive science because of huge data sets produced by high throughput molecular biological experiments in diverse areas including the fields of genomics, transcriptomics, proteomics, and metabolomics. These huge datasets have paved the way for system-level analysis of the processes and subprocesses of the cell. For system-level understanding, initially the elements of a system are connected based on their mutual relations and a network is formed. Among omics researchers, construction and analysis of biological networks have become highly popular. In this review, we briefly discuss both the biological background and topological properties of major types of omics networks to facilitate a comprehensive understanding and to conceptualize the foundation of network biology. PMID:26491677

  9. Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures.

    PubMed

    Dionne, Justine; Lefèvre, Thierry; Auger, Michèle

    2016-01-01

    To plentifully benefit from its properties (mechanical, optical, biological) and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA) silk of Araneus diadematus (AD) and Nephila clavipes (NC) has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc.) are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively) as compared to NC (37% and 51°, respectively). β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro) that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads. PMID:27548146

  10. Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures

    PubMed Central

    Dionne, Justine; Lefèvre, Thierry; Auger, Michèle

    2016-01-01

    To plentifully benefit from its properties (mechanical, optical, biological) and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA) silk of Araneus diadematus (AD) and Nephila clavipes (NC) has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc.) are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively) as compared to NC (37% and 51°, respectively). β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro) that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads. PMID:27548146

  11. Molecular and physiological responses of trees to waterlogging stress.

    PubMed

    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. PMID:24611781

  12. Molecular and physiological responses of trees to waterlogging stress.

    PubMed

    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.

  13. HOX genes: Major actors in resistance to selective endocrine response modifiers.

    PubMed

    Jin, Kideok; Sukumar, Saraswati

    2016-04-01

    Long term treatment with therapies aimed at blocking the estrogen- (ER) or androgen receptor (AR) action often leads to the development of resistance to selective modulators of the estrogen receptor (SERMs) in ERα-positive breast cancer, or of the androgen receptor (SARMs) in AR-positive prostate cancer. Many underlying molecular events that confer resistance are known, but a unifying theme is yet to be revealed. Receptor tyrosine kinases (RTKs) such EGFR, ERBB2 and IGF1R are major mediators that can directly alter cellular response to the SERM, tamoxifen, but the mechanisms underlying increased expression of RTKs are not clear. A number of HOX genes and microRNAs and non-coding RNAs residing in the HOX cluster, have been identified as important independent predictors of endocrine resistant breast cancer. Recently, convincing evidence has accumulated that several members belonging to the four different HOX clusters contribute to endocrine therapy resistant breast cancer, but the mechanisms remain obscure. In this article, we have reviewed recent progress in understanding of the functioning of HOX genes and regulation of their expression by hormones. We also discuss, in particular, the contributions of several members of the HOX gene family to endocrine resistant breast cancer.

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

    PubMed Central

    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

  15. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

    PubMed Central

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

    2013-01-01

    Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

  16. Photodynamic therapy: Biophysical mechanisms and molecular responses

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya

    70), in response to mTHPC-PDT. The studies are performed using a murine tumor cell line transfected with a plasmid containing the gene for Green Fluorescent Protein (GFP) under the control of an hsp70 promoter. We obtain increased levels of GFP fluorescence at a cellular level and in vivo in response to sub-lethal doses of mTHPC-PDT. These results demonstrate the potential of using fluorescent reporter proteins as biomarkers of PDT-induced oxidative stress.

  17. Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy

    PubMed Central

    Murcia, Oscar; Juárez, Miriam; Hernández-Illán, Eva; Egoavil, Cecilia; Giner-Calabuig, Mar; Rodríguez-Soler, María; Jover, Rodrigo

    2016-01-01

    Molecular advances support the existence of an alternative pathway of colorectal carcinogenesis that is based on the hypermethylation of specific DNA regions that silences tumor suppressor genes. This alternative pathway has been called the serrated pathway due to the serrated appearance of tumors in histological analysis. New classifications for colorectal cancer (CRC) were proposed recently based on genetic profiles that show four types of molecular alterations: BRAF gene mutations, KRAS gene mutations, microsatellite instability, and hypermethylation of CpG islands. This review summarizes what is known about the serrated pathway of CRC, including CRC molecular and clinical features, prognosis, and response to chemotherapy. PMID:27053844

  18. Molecular Evolution of the Yersinia Major Outer Membrane Protein C (OmpC)

    PubMed Central

    Stenkova, Anna M.; Bystritskaya, Evgeniya P.; Guzev, Konstantin V.; Rakin, Alexander V.; Isaeva, Marina P.

    2016-01-01

    The genus Yersinia includes species with a wide range of eukaryotic hosts (from fish, insects, and plants to mammals and humans). One of the major outer membrane proteins, the porin OmpC, is preferentially expressed in the host gut, where osmotic pressure, temperature, and the concentrations of nutrients and toxic products are relatively high. We consider here the molecular evolution and phylogeny of Yersinia ompC. The maximum likelihood gene tree reflects the macroevolution processes occurring within the genus Yersinia. Positive selection and horizontal gene transfer are the key factors of ompC diversification, and intraspecies recombination was revealed in two Yersinia species. The impact of recombination on ompC evolution was different from that of another major porin gene, ompF, possibly due to the emergence of additional functions and conservation of the basic transport function. The predicted antigenic determinants of OmpC were located in rapidly evolving regions, which may indicate the evolutionary mechanisms of Yersinia adaptation to the host immune system. PMID:27578962

  19. Molecular Evolution of the Yersinia Major Outer Membrane Protein C (OmpC).

    PubMed

    Stenkova, Anna M; Bystritskaya, Evgeniya P; Guzev, Konstantin V; Rakin, Alexander V; Isaeva, Marina P

    2016-01-01

    The genus Yersinia includes species with a wide range of eukaryotic hosts (from fish, insects, and plants to mammals and humans). One of the major outer membrane proteins, the porin OmpC, is preferentially expressed in the host gut, where osmotic pressure, temperature, and the concentrations of nutrients and toxic products are relatively high. We consider here the molecular evolution and phylogeny of Yersinia ompC. The maximum likelihood gene tree reflects the macroevolution processes occurring within the genus Yersinia. Positive selection and horizontal gene transfer are the key factors of ompC diversification, and intraspecies recombination was revealed in two Yersinia species. The impact of recombination on ompC evolution was different from that of another major porin gene, ompF, possibly due to the emergence of additional functions and conservation of the basic transport function. The predicted antigenic determinants of OmpC were located in rapidly evolving regions, which may indicate the evolutionary mechanisms of Yersinia adaptation to the host immune system. PMID:27578962

  20. Molecular Weight Effects on the Viscoelastic Response of a Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2000-01-01

    The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC -SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of each material with different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have increased creep compliance and creep compliance rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of approximately 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly.

  1. Devising and Investigating Benefits of Interconnected Interventions to Promote Education Majors' Culturally Responsive Teaching

    ERIC Educational Resources Information Center

    Richards, Janet C.

    2011-01-01

    For five years I have supervised a summer literacy camp that connects graduate education majors with students from diverse ethnicities. Each summer I noted I inadequately challenged the education majors to extend their knowledge, examine their attitudes, and expand their abilities to offer culturally responsive literacy instruction to students in…

  2. Leaders of the Pack: Responsibilities and Experiences of Collegiate Drum Majors

    ERIC Educational Resources Information Center

    Brewer, Wesley D.

    2009-01-01

    This study explored the responsibilities and experiences of three collegiate drum majors as student leaders of a marching band at a major university. Marching band continues to be a prevalent and highly visible aspect of music education in the United States. The preparation and utilization of student leaders in music remains common, but little…

  3. Molecular genetics of the swine major histocompatibility complex, the SLA complex.

    PubMed

    Lunney, Joan K; Ho, Chak-Sum; Wysocki, Michal; Smith, Douglas M

    2009-03-01

    The swine major histocompatibility complex (MHC) or swine leukocyte antigen (SLA) complex is one of the most gene-dense regions in the swine genome. It consists of three major gene clusters, the SLA class I, class III and class II regions, that span approximately 1.1, 0.7 and 0.5Mb, respectively, making the swine MHC the smallest among mammalian MHC so far examined and the only one known to span the centromere. This review summarizes recent updates to the Immuno Polymorphism Database-MHC (IPD-MHC) website (http://www.ebi.ac.uk/ipd/mhc/sla/) which serves as the repository for maintaining a list of all SLA recognized genes and their allelic sequences. It reviews the expression of SLA proteins on cell subsets and their role in antigen presentation and regulating immune responses. It concludes by discussing the role of SLA genes in swine models of transplantation, xenotransplantation, cancer and allergy and in swine production traits and responses to infectious disease and vaccines.

  4. Proximity to major roadways is a risk factor for airway hyper-responsiveness in adults

    PubMed Central

    Riley, Shannon; Wallace, Julie; Nair, Parameswaran

    2012-01-01

    BACKGROUND: Proximity to major roads is reported to be associated with asthma and airway hyper-responsiveness in children. Similar studies using objective measurements in adults are not available in Canada. OBJECTIVE: To test the hypothesis that adult asthmatic patients who live close to major roads and highways in an urban environment are at a risk of moderate to severe airway hyper-responsiveness. METHODS: Airway responsiveness was determined using methacholine bronchial provocation (PC20) tests in a cohort of 2625 patients who attended an outpatient clinic in Hamilton, Ontario. Patient addresses were geocoded in a geographic information system to determine proximity to major roads and highways. Multivariate linear and multinomial regression analyses were used to assess whether proximity to roads was a risk factor for airway hyper-responsiveness as measured by PC20 methacholine. RESULTS: Patients who lived within 200 m of a major road had increased odds (OR 1.38 [95% CI 1.04 to 1.85]) of having moderate airway hyper-responsiveness (0.25 mg/mL response (PC20 >16 mg/mL). Spatial analysis also revealed that the majority of patients with severe airway hyper-responsiveness lived within the urban core of the city while those with moderate to mild hyper-responsiveness were also dispersed in rural areas. CONCLUSIONS: In an adult population of patients attending an outpatient respiratory clinic in Hamilton, living close to major roadways was associated with an increased risk of moderate airway hyper-responsiveness. This correlation suggests that exposure to traffic emissions may provoke the pathology of airway hyper-responsiveness leading to variable airflow obstruction. PMID:22536577

  5. Molecular polymorphism and expression analysis of MHC class II B gene from red sea bream (Chrysophrys major).

    PubMed

    Chen, Song-Lin; Zhang, Yu-Xi; Xu, Mei-Yu; Ji, Xiang-Shan; Yu, Guo-Cai; Dong, Cheng-Fang

    2006-01-01

    MHC class II (major histocompatibility complex class II) plays an important role in the immune response of vertebrates. Its function is to present antigenic peptides to the T-cell receptor. In order to study the function and molecular polymorphism of class II B gene in fish, we have isolated cDNAs encoding class II B from spleen cDNA library of red sea bream (Chrysophrys major) by using EST sequencing, and examined genomic organization, molecular polymorphism and expression of red sea bream class II B gene. As in other vertebrates, five exons and four introns were identified in red sea bream class II B gene. Seven class II B alleles were identified from seven individuals of red sea bream. The deduced amino acid sequence of red sea bream MHC class II B 1(Chma-DAB*0101) had 87.1, 85.1, 87.1, 90.4, 87.1, 90.8% identity with those of red sea bream class II B 2, 3, 4, 5, 6, 7(Chma-DAB*0201-Chma-DAB*0701), respectively, and had 75.2, 74.5, 55.9, 55.1, 34.3 and 30.4% identity with those of striped sea bass, cichlid, rainbow trout, Atlantic salmon, mouse and human, respectively. Four different class II B alleles were observed in a single individual and two different 3' untranslated region (3' UTR) sequences from this individual may infer the existence of two loci at least. Semi-quantitative RT-PCR demonstrated that high expression was detected in liver, head kidney, kidney, intestine, gill, stomach, hear and spleen, low expression in muscle and blood. Challenge of red sea bream with the pathogenic bacteria, Vibrio anguillarum, resulted in a significant decrease in the expression of MHC class II B mRNA from 5 to 72 h after infection in liver, spleen, head kidney and intestine, followed by a recovery to normal level after 96 h.

  6. Low-molecular-weight sulfonates, a major substrate for sulfate reducers in marine microbial mats.

    PubMed

    Visscher, P T; Gritzer, R F; Leadbetter, E R

    1999-08-01

    Several low-molecular-weight sulfonates were added to microbial mat slurries to investigate their effects on sulfate reduction. Instantaneous production of sulfide occurred after taurine and cysteate were added to all of the microbial mats tested. The rates of production in the presence of taurine and cysteate were 35 and 24 microM HS(-) h(-1) in a stromatolite mat, 38 and 36 microM HS(-) h(-1) in a salt pond mat, and 27 and 18 microM HS(-) h(-1) in a salt marsh mat, respectively. The traditionally used substrates lactate and acetate stimulated the rate of sulfide production 3 to 10 times more than taurine and cysteate stimulated the rate of sulfide production in all mats, but when ethanol, glycolate, and glutamate were added to stromatolite mat slurries, the resulting increases were similar to the increases observed with taurine and cysteate. Isethionate, sulfosuccinate, and sulfobenzoate were tested only with the stromatolite mat slurry, and these compounds had much smaller effects on sulfide production. Addition of molybdate resulted in a greater inhibitory effect on acetate and lactate utilization than on sulfonate use, suggesting that different metabolic pathways were involved. In all of the mats tested taurine and cysteate were present in the pore water at nanomolar to micromolar concentrations. An enrichment culture from the stromatolite mat was obtained on cysteate in a medium lacking sulfate and incubated anaerobically. The rate of cysteate consumption by this enrichment culture was 1.6 pmol cell(-1) h(-1). Compared to the results of slurry studies, this rate suggests that organisms with properties similar to the properties of this enrichment culture are a major constituent of the sulfidogenic population. In addition, taurine was consumed at some of highest dilutions obtained from most-probable-number enrichment cultures obtained from stromatolite samples. Based on our comparison of the sulfide production rates found in various mats, low-molecular

  7. 7 CFR 22.203 - Major responsibilities under title VI, Sec. 603.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Roles and Responsibilities of Federal Government § 22.203 Major responsibilities under title VI, Sec... program. Included in this program would be pertinent Federal departments and agencies which might... to this section of the Act. (iii) At the regional level, the Federal Regional Councils shall...

  8. 7 CFR 22.203 - Major responsibilities under title VI, Sec. 603.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Roles and Responsibilities of Federal Government § 22.203 Major responsibilities under title VI, Sec... program. Included in this program would be pertinent Federal departments and agencies which might... to this section of the Act. (iii) At the regional level, the Federal Regional Councils shall...

  9. 7 CFR 22.203 - Major responsibilities under title VI, Sec. 603.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Roles and Responsibilities of Federal Government § 22.203 Major responsibilities under title VI, Sec... program. Included in this program would be pertinent Federal departments and agencies which might... to this section of the Act. (iii) At the regional level, the Federal Regional Councils shall...

  10. In vivo/In vitro immune responses to L. major isolates from patients with no clinical response to Glucantime

    PubMed Central

    Saberi, Sedigheh; Arjmand, Reza; Soleimanifard, Simindokht; Khamesipour, Ali; Hosseini, Seyed Mohsen; Salehi, Mansoor; Varshosaz, Jaleh; Palizban, Abbas Ali; Hejazi, Seyed Hossein

    2016-01-01

    Background: Leishmaniasis is a major health problem in some endemic areas of tropical and subtropical areas of the world. Interleukin-12 (IL-12) and interferon gamma (IFN-γ) are essential cytokines associated with initiation of Th1 response. The main objective of this study was to evaluate of the type of immune response to L. major isolates from patients with no clinical response to antimonite (Glucantime). Materials and Methods: This experimental study was carried out during 2013–2014. In the current study Leishmania major were isolated from 10 CL patients with a history of at least one course of treatment with Meglumine antimonate (Sb5). The isolates were used to evaluate in vitro and in vivo response to Sb5. J774 murine macrophage cell line was used for in vitro tests and Balb/c mice was used for in vivo studies. IL-12 gene expression was evaluated using Real-time PCR and IFN-γ serum level was quantified using ELISA technique. SPSS (version: 20), analysis of Covariance (ANCOVA) was used for statistical analysis. Results: PCR results confirmed that all 10 isolates were L. major. The mean of IL-12 gene expression in vitro, in vivo and IFN-γ serum levels (pg/ml) after 2 and 3 weeks treatment in vivo, increased significantly following the treatment with Glucantime in the two groups of Balb/c mice infected either with patients' isolates or standard L. major. No significant difference was seen between the patients' isolates and standard species. Conclusions: Although the L. major were isolated from patients with active lesion and no clinical response to Glucantime after at least one courses of Glucantime treatment but in vivo and in vitro immune response of L. major isolates showed no difference between the patients' isolates and standard L. major. PMID:27563636

  11. Molecular cloning of cecropin B responsive endonucleases in Yersinia ruckeri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have previously demonstrated that Yersinia ruckeri resists cecropin B in an inducible manner. In this study, we sought to identify the molecular changes responsible for the inducible cecropin B resistance of Y. ruckeri. Differences in gene expression associated with the inducible resistance were ...

  12. Veni, vidi, vici: in vivo molecular imaging of immune response.

    PubMed

    Gross, Shimon; Moss, Britney L; Piwnica-Worms, David

    2007-10-01

    "I came, I saw, I conquered," Julius Caesar proclaimed, highlighting the importance of direct visualization as a winning strategy. Continuing the "From the Field" series (see Editorial [2007] 26, 131), Gross et al. summarize how modern molecular imaging techniques can successfully dissect the complexities of immune response in vivo. PMID:17967405

  13. Physiology of digestion and the molecular characterization of the major digestive enzymes from Periplaneta americana.

    PubMed

    Tamaki, Fábio K; Pimentel, André C; Dias, Alcides B; Cardoso, Christiane; Ribeiro, Alberto F; Ferreira, Clélia; Terra, Walter R

    2014-11-01

    Cockroaches are among the first insects to appear in the fossil record. This work is part of ongoing research on insects at critical points in the evolutionary tree to disclose evolutionary trends in the digestive characteristics of insects. A transcriptome (454 Roche platform) of the midgut of Periplanetaamericana was searched for sequences of digestive enzymes. The selected sequences were manually curated. The complete or nearly complete sequences showing all characteristic motifs and highly expressed (reads counting) had their predicted sequences checked by cloning and Sanger sequencing. There are two chitinases (lacking mucin and chitin-binding domains), one amylase, two α- and three β-glucosidases, one β-galactosidase, two aminopeptidases (none of the N-group), one chymotrypsin, 5 trypsins, and none β-glucanase. Electrophoretic and enzymological data agreed with transcriptome data in showing that there is a single β-galactosidase, two α-glucosidases, one preferring as substrate maltase and the other aryl α-glucoside, and two β-glucosidases. Chromatographic and enzymological data identified 4 trypsins, one chymotrypsin (also found in the transcriptome), and one non-identified proteinase. The major digestive trypsin is identifiable to a major P. americana allergen (Per a 10). The lack of β-glucanase expression in midguts was confirmed, thus lending support to claims that those enzymes are salivary. A salivary amylase was molecularly cloned and shown to be different from the one from the midgut. Enzyme distribution showed that most digestion occurs under the action of salivary and midgut enzymes in the foregut and anterior midgut, except the posterior terminal digestion of proteins. A counter-flux of fluid may be functional in the midgut of the cockroach to explain the low excretory rate of digestive enzymes. Ultrastructural and immunocytochemical localization data showed that amylase and trypsin are released by both merocrine and apocrine secretion

  14. Molecular mechanisms of the plant heat stress response

    SciTech Connect

    Qu, Ai-Li; Ding, Yan-Fei; Jiang, Qiong; Zhu, Cheng

    2013-03-08

    Highlights: ► This review elaborates the response networks of heat stress in plants. ► It elaborates proteins responding to heat stress in special physiological period. ► The proteins and pathways have formed a basic network of the heat stress response. ► Achievements of the various technologies are also combined. -- Abstract: High temperature has become a global concern, which seriously affects the growth and production of plants, particularly crops. Thus, the molecular mechanism of the heat stress response and breeding of heat-tolerant plants is necessary to protect food production and ensure crop safety. This review elaborates on the response networks of heat stress in plants, including the Hsf and Hsp response pathways, the response of ROS and the network of the hormones. In addition, the production of heat stress response elements during particular physiological periods of the plant is described. We also discuss the existing problems and future prospects concerning the molecular mechanisms of the heat stress response in plants.

  15. Molecular cytogenetic analysis and genomic organization of major DNA repeats in castor bean (Ricinus communis L.).

    PubMed

    Alexandrov, O S; Karlov, G I

    2016-04-01

    This article addresses the bioinformatic, molecular genetic, and cytogenetic study of castor bean (Ricinus communis, 2n = 20), which belongs to the monotypic Ricinus genus within the Euphorbiaceae family. Because castor bean chromosomes are small, karyotypic studies are difficult. However, the use of DNA repeats has yielded new prospects for karyotypic research and genome characterization. In the present study, major DNA repeat sequences were identified, characterized and localized on mitotic metaphase and meiotic pachytene chromosomes. Analyses of the nucleotide composition, curvature models, and FISH localization of the rcsat39 repeat suggest that this repeat plays a key role in building heterochromatic arrays in castor bean. Additionally, the rcsat390 sequences were determined to be chromosome-specific repeats located in the pericentromeric region of mitotic chromosome A (pachytene chromosome 1). The localization of rcsat39, rcsat390, 45S and 5S rDNA genes allowed for the development of cytogenetic landmarks for chromosome identification. General questions linked to heterochromatin formation, DNA repeat distribution, and the evolutionary emergence of the genome are discussed. The article may be of interest to biologists studying small genome organization and short monomer DNA repeats. PMID:26589420

  16. Molecular cytogenetic analysis and genomic organization of major DNA repeats in castor bean (Ricinus communis L.).

    PubMed

    Alexandrov, O S; Karlov, G I

    2016-04-01

    This article addresses the bioinformatic, molecular genetic, and cytogenetic study of castor bean (Ricinus communis, 2n = 20), which belongs to the monotypic Ricinus genus within the Euphorbiaceae family. Because castor bean chromosomes are small, karyotypic studies are difficult. However, the use of DNA repeats has yielded new prospects for karyotypic research and genome characterization. In the present study, major DNA repeat sequences were identified, characterized and localized on mitotic metaphase and meiotic pachytene chromosomes. Analyses of the nucleotide composition, curvature models, and FISH localization of the rcsat39 repeat suggest that this repeat plays a key role in building heterochromatic arrays in castor bean. Additionally, the rcsat390 sequences were determined to be chromosome-specific repeats located in the pericentromeric region of mitotic chromosome A (pachytene chromosome 1). The localization of rcsat39, rcsat390, 45S and 5S rDNA genes allowed for the development of cytogenetic landmarks for chromosome identification. General questions linked to heterochromatin formation, DNA repeat distribution, and the evolutionary emergence of the genome are discussed. The article may be of interest to biologists studying small genome organization and short monomer DNA repeats.

  17. Leishmania major, the predominant Leishmania species responsible for cutaneous leishmaniasis in Mali.

    PubMed

    Paz, Carlos; Samake, Sibiry; Anderson, Jennifer M; Faye, Ousmane; Traore, Pierre; Tall, Koureishi; Cisse, Moumine; Keita, Somita; Valenzuela, Jesus G; Doumbia, Seydou

    2013-03-01

    Leishmania major is the only species of Leishmania known to cause cutaneous leishmanisis (CL) in Mali. We amplified Leishmania DNA stored on archived Giemsa-stained dermal scraping slides obtained from self-referral patients with clinically suspected CL seen in the Center National d'Appui A La Lutte Contre La Maladie (CNAM) in Bamako, Mali, to determine if any other Leishmania species were responsible for CL in Mali and evaluate its geographic distribution. Polymerase chain reaction (PCR) amplification was performed using a Leishmania species-specific primer pair that can amplify DNA from L. major, L. tropica, L. infantum, and L. donovani parasites, possible causative agents of CL in Mali. L. major was the only species detected in 41 microscopically confirmed cases of CL from five regions of Mali (Kayes, Koulikoro, Ségou, Mopti, and Tombouctou). These results implicate L. major as the predominant, possibly exclusive species responsible for CL in Mali.

  18. NF1 Gene Mutations Represent the Major Molecular Event Underlying Neurofibromatosis-Noonan Syndrome

    PubMed Central

    De Luca, Alessandro; Bottillo, Irene; Sarkozy, Anna; Carta, Claudio; Neri, Cinzia; Bellacchio, Emanuele; Schirinzi, Annalisa; Conti, Emanuela; Zampino, Giuseppe; Battaglia, Agatino; Majore, Silvia; Rinaldi, Maria M.; Carella, Massimo; Marino, Bruno; Pizzuti, Antonio; Digilio, Maria Cristina; Tartaglia, Marco; Dallapiccola, Bruno

    2005-01-01

    Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11–27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals. PMID:16380919

  19. Purification, characterization and molecular cloning of the major chitinase from Tenebrio molitor larval midgut.

    PubMed

    Genta, Fernando A; Blanes, Lucas; Cristofoletti, Plínio T; do Lago, Claudimir L; Terra, Walter R; Ferreira, Clélia

    2006-10-01

    Insect chitinases are involved in degradation of chitin from the exoskeleton cuticle or from midgut peritrophic membrane during molts. cDNAs coding for insect cuticular and gut chitinases were cloned, but only chitinases from moulting fluid were purified and characterized. In this study the major digestive chitinase from T. molitor midgut (TmChi) was purified to homogeneity, characterized and sequenced after cDNA cloning. TmChi is secreted by midgut epithelial cells, has a molecular weight of 44 kDa and is unstable in the presence of midgut proteinases. TmChi shows strong substrate inhibition when acting on umbelliferyl-derivatives of chitobio- and chitotriosaccharides, but has normal Michaelis kinetics with the N-acetylglucosamine derivative as substrate. TmChi has very low activity against colloidal chitin, but effectively converts oligosaccharides to shorter fragments. The best substrate for TmChi is chitopentaose, with highest k(cat)/K(M) value. Sequence analysis and chemical modification experiments showed that the TmChi active site contains carboxylic groups and a tryptophane, which are known to be important for catalysis in family 18 chitinases. Modification with p-hidroximercuribenzoate of a cysteine residue, which is exposed after substrate binding, leads to complete inactivation of the enzyme. TmChi mRNA encodes a signal peptide plus a protein with 37 kDa and high similarity with other insect chitinases from family 18. Surprisingly, this gene does not encode the C-terminal Ser-Thr-rich connector and chitin-binding domain normally present in chitinases. The special features of TmChi probably result from its adaptation to digest chitin-rich food without damaging the peritrophic membrane.

  20. Structural polymorphism of the major capsid protein of a double-stranded RNA virus: an amphipathic alpha helix as a molecular switch.

    PubMed

    Saugar, Irene; Luque, Daniel; Oña, Ana; Rodríguez, José F; Carrascosa, José L; Trus, Benes L; Castón, José R

    2005-07-01

    The infectious bursal disease virus T=13 viral particle is composed of two major proteins, VP2 and VP3. Here, we show that the molecular basis of the conformational flexibility of the major capsid protein precursor, pVP2, is an amphipatic alpha helix formed by the sequence GFKDIIRAIR. VP2 containing this alpha helix is able to assemble into the T=13 capsid only when expressed as a chimeric protein with an N-terminal His tag. An amphiphilic alpha helix, which acts as a conformational switch, is thus responsible for the inherent structural polymorphism of VP2. The His tag mimics the VP3 C-terminal region closely and acts as a molecular triggering factor. Using cryo-electron microscopy difference imaging, both polypeptide elements were detected on the capsid inner surface. We propose that electrostatic interactions between these two morphogenic elements are transmitted to VP2 to acquire the competent conformations for capsid assembly.

  1. Molecular Magnetic Resonance Imaging of Tumor Response to Therapy

    PubMed Central

    Shuhendler, Adam J.; Ye, Deju; Brewer, Kimberly D.; Bazalova-Carter, Magdalena; Lee, Kyung-Hyun; Kempen, Paul; Dane Wittrup, K.; Graves, Edward E.; Rutt, Brian; Rao, Jianghong

    2015-01-01

    Personalized cancer medicine requires measurement of therapeutic efficacy as early as possible, which is optimally achieved by three-dimensional imaging given the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images of both anatomy and cellular responses, if acquired with a molecular imaging contrast agent. The poor sensitivity of MRI has limited the development of activatable molecular MR contrast agents. To overcome this limitation of molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular level changes through nanoaggregation, enhancing tissue retention and spin-lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and following a single imaging session, C-SNAM MRI accurately measured the response of tumors to either metronomic chemotherapy or radiation therapy, where the degree of signal enhancement is prognostic of long-term therapeutic efficacy. Importantly, C-SNAM is inert to immune activation, permitting radiation therapy monitoring. PMID:26440059

  2. The European Union Integrated Political Crisis Response Arrangements: Improving the European Union's Major Crisis Response Coordination Capacities.

    PubMed

    de Miguel Beriain, Iñigo; Atienza-Macías, Elena; Armaza, Emilio Armaza

    2015-06-01

    In recent years, the European Union (EU) has progressively assumed more and more of a primary role in crisis response coordination. The EU Integrated Political Crisis Response arrangements (IPCR) were recently approved to facilitate this task. These new agreements, which substitute for the Crisis Coordination Agreements, will add more flexibility to crisis response mechanisms in the EU. They will also strengthen cooperation between the different relevant agents in a major crisis situation and create new useful tools, such as the Integrated Situational Awareness and Analysis. Their real performance still needs to be fully tested, but some weakness can already be foreseen. This article provides a deep analysis of this new legislation.

  3. Family business: multiple members of major phytohormone classes orchestrate plant stress responses.

    PubMed

    Erb, Matthias; Glauser, Gaetan

    2010-09-10

    Low-molecular-weight compounds such as jasmonic, abscisic and salicylic acids are commonly thought to be regulators of plant stress responses. However, it is becoming clear that these molecules, often referred to as phytohormones, are only a part of bigger groups of compounds with biological activity. We propose that the concept of "hormone families" may help to better understand plant physiological responses by taking into account not only the alleged main regulators, but also their precursors, conjugates and catabolites. Novel approaches to profile potentially active compounds in plants are discussed. PMID:20648494

  4. Family business: multiple members of major phytohormone classes orchestrate plant stress responses.

    PubMed

    Erb, Matthias; Glauser, Gaetan

    2010-09-10

    Low-molecular-weight compounds such as jasmonic, abscisic and salicylic acids are commonly thought to be regulators of plant stress responses. However, it is becoming clear that these molecules, often referred to as phytohormones, are only a part of bigger groups of compounds with biological activity. We propose that the concept of "hormone families" may help to better understand plant physiological responses by taking into account not only the alleged main regulators, but also their precursors, conjugates and catabolites. Novel approaches to profile potentially active compounds in plants are discussed.

  5. Childhood Maltreatment and Differential Treatment Response and Recurrence in Adult Major Depressive Disorder

    ERIC Educational Resources Information Center

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

    2012-01-01

    Objective: 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. Method:…

  6. Student Response to a Partial Inversion of an Organic Chemistry Course for Non-Chemistry Majors

    ERIC Educational Resources Information Center

    Rein, Kathleen S.; Brookes, David T.

    2015-01-01

    We report the student response to a two-year transformation of a one-semester organic chemistry course for nonchemistry majors. The transformed course adopted a peer led team learning approach and incorporated case studies. Student attitudes toward the course transformation were assessed throughout the semester, and adjustments to the methods were…

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

    EPA Science Inventory

    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...

  8. 7 CFR 22.203 - Major responsibilities under title VI, Sec. 603.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Major responsibilities under title VI, Sec. 603. 22.203 Section 22.203 Agriculture Office of the Secretary of Agriculture RURAL DEVELOPMENT COORDINATION... Secretary of Agriculture with providing leadership in the development of a nationwide rural...

  9. Seismic Safety Margins Research Program. Phase I, final report. Major structure response (Project IV). Volume 5

    SciTech Connect

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

    1981-05-01

    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.

  10. Ethnic Majority/Minority Status: Children's Interactions and Affective Responses to Music.

    ERIC Educational Resources Information Center

    McCrary, Jan

    2000-01-01

    Examines the effect of classroom ethnic majority/minority status on third-, fifth-, and seventh-grade children's responses (N=118)while listening to and discussing the music of a Latin salsa artist, African-American rhythm and blues artist, and a European-American folk artist. Investigates the students' artist and music preferences. (CMK)

  11. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.

    PubMed

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L; Phu, My; Spann, Timothy M; McCollum, Thomas G; Dandekar, Abhaya M

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials.

  12. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease

    PubMed Central

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L.; Phu, My; Spann, Timothy M.; McCollum, Thomas G.; Dandekar, Abhaya M.

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. PMID:27459099

  13. Molecular Responses to Small Regulating Molecules against Huanglongbing Disease.

    PubMed

    Martinelli, Federico; Dolan, David; Fileccia, Veronica; Reagan, Russell L; Phu, My; Spann, Timothy M; McCollum, Thomas G; Dandekar, Abhaya M

    2016-01-01

    Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials. PMID:27459099

  14. Molecular Response of Crop Plants to Engineered Nanomaterials.

    PubMed

    Pagano, Luca; Servin, Alia D; De La Torre-Roche, Roberto; Mukherjee, Arnab; Majumdar, Sanghamitra; Hawthorne, Joseph; Marmiroli, Marta; Maestri, Elena; Marra, Robert E; Isch, Susan M; Dhankher, Om Parkash; White, Jason C; Marmiroli, Nelson

    2016-07-01

    Functional toxicology has enabled the identification of genes involved in conferring tolerance and sensitivity to engineered nanomaterial (ENM) exposure in the model plant Arabidopsis thaliana (L.) Heynh. Several genes were found to be involved in metabolic functions, stress response, transport, protein synthesis, and DNA repair. Consequently, analysis of physiological parameters, metal content (through ICP-MS quantification), and gene expression (by RT-qPCR) of A. thaliana orthologue genes were performed across different plant species of agronomic interest to highlight putative biomarkers of exposure and effect related to ENMs. This approach led to the identification of molecular markers in Solanum lycopersicum L. and Cucurbita pepo L. (tomato and zucchini) that might not only indicate exposure to ENMs (CuO, CeO2, and La2O3) but also provide mechanistic insight into response to these materials. Through Gene Ontology (GO) analysis, the target genes were mapped in complex interatomic networks representing molecular pathways, cellular components, and biological processes involved in ENM response. The transcriptional response of 38 (out of 204) candidate genes studied varied according to particle type, size, and plant species. Importantly, some of the genes studied showed potential as biomarkers of ENM exposure and effect and may be useful for risk assessment in foods and in the environment. PMID:27301997

  15. Shear Viscous Response of Molecularly Thin Liquid Films

    NASA Astrophysics Data System (ADS)

    Tschirhart, Charles; Troian, Sandra

    2014-11-01

    Fluids that exhibit Newtonian response at the macroscale can display interesting deviations at the nanoscale caused by internal fluid microstructure or conformational entropy reduction near an adjacent solid boundary. Such deviations signal the breakdown of the continuum and isotropic fluid approximations at molecular length scales. These effects are particularly pronounced near the interface separating a liquid film from a supporting solid substrate where molecular layering in the fluid can result in inhomogeneity in the shear viscosity. Here we describe ellipsometric measurements of the surface deformation of non-volatile liquid nanofilms subject to a constant interfacial shear stress. For simple Newtonian response, the slope of the deformation can be used to extract the value of the shear viscosity in ultrathin films, which in our experiments range from 2 - 200 nm in thickness. For complex films, we observe deviations from linear deformation which require augmentation of the analytic model normally used to describe the viscous response. These findings may be helpful for improved parametrization of the shear response of supported free surface films as well as course grained models for nanofluidic applications. Support from the Fred and Jean Felberg and Winifred and Robert Gardner Summer Undergraduate Research Fellowships is gratefully acknowledged.

  16. Molecular circuits, biological switches, and nonlinear dose-response relationships.

    PubMed Central

    Andersen, Melvin E; Yang, Raymond S H; French, C Tenley; Chubb, Laura S; Dennison, James E

    2002-01-01

    Signaling motifs (nuclear transcriptional receptors, kinase/phosphatase cascades, G-coupled protein receptors, etc.) have composite dose-response behaviors in relation to concentrations of protein receptors and endogenous signaling molecules. "Molecular circuits" include the biological components and their interactions that comprise the workings of these signaling motifs. Many of these molecular circuits have nonlinear dose-response behaviors for endogenous ligands and for exogenous toxicants, acting as switches with "all-or-none" responses over a narrow range of concentration. In turn, these biological switches regulate large-scale cellular processes, e.g., commitment to cell division, cell differentiation, and phenotypic alterations. Biologically based dose-response (BBDR) models accounting for these biological switches would improve risk assessment for many nonlinear processes in toxicology. These BBDR models must account for normal control of the signaling motifs and for perturbations by toxic compounds. We describe several of these biological switches, current tools available for constructing BBDR models of these processes, and the potential value of these models in risk assessment. PMID:12634127

  17. Pretreatment anterior cingulate activity predicts antidepressant treatment response in major depressive episodes.

    PubMed

    Rentzsch, Johannes; Adli, Mazda; Wiethoff, Katja; Gómez-Carrillo de Castro, Ana; Gallinat, Jürgen

    2014-04-01

    Major depressive disorder leads to substantial individual and socioeconomic costs. Despite the ongoing efforts to improve the treatment for this condition, a trial-and-error approach until an individually effective treatment is established still dominates clinical practice. Searching for clinically useful treatment response predictors is one of the most promising strategies to change this quandary therapeutic situation. This study evaluated the predictive value of a biological and a clinical predictor, as well as a combination of both. Pretreatment EEGs of 31 patients with a major depressive episode were analyzed with neuroelectric brain imaging technique to assess cerebral oscillations related to treatment response. Early improvement of symptoms served as a clinical predictor. Treatment response was assessed after 4 weeks of antidepressant treatment. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders. Slow-frequency power in this region was found to predict response with good sensitivity (82 %) and specificity (100 %), while early improvement showed lower accuracy (73 % sensitivity and 65 % specificity). Combining both parameters did not further improve predictive accuracy. Pretreatment activity within the anterior cingulate cortex is related to antidepressive treatment response. Our results support the search for biological treatment response predictors using electric brain activity. This technique is advantageous due to its low individual and socioeconomic burden. The benefits of combining both, a clinically and a biologically based predictor, should be further evaluated using larger sample sizes.

  18. Molecular design of responsive fluids: molecular dynamics studies of viscoelastic surfactant solutions

    NASA Astrophysics Data System (ADS)

    Boek, E. S.; Jusufi, A.; Löwen, H.; Maitland, G. C.

    2002-10-01

    Understanding how macroscopic properties depend on intermolecular interactions for complex fluid systems is an enormous challenge in statistical mechanics. This issue is of particular importance for designing optimal industrial fluid formulations such as responsive oilfield fluids, based on viscoelastic surfactant solutions. We have carried out extensive molecular dynamics simulations, resolving the full chemical details in order to study how the structure of the lamellar phase of viscoelastic surfactant solutions depends on the head group (HG) chemistry of the surfactant. In particular, we consider anionic carboxylate and quaternary ammonium HGs with erucyl tails in aqueous solutions together with their sodium and chloride counterions at room temperature. We find a strong HG dependence of the lamellar structure as characterized by suitable pair correlation functions and density distributions. The depth of penetration of water into the bilayer membrane, the nature of counterion condensation on the HGs and even the order and correlation of the tails in the lamellae depend sensitively on the chemical details of the HG. We also determine the compressibility of the lamellar system as a first step to using atom-resolved molecular dynamics in order to link the molecular and macroscopic scales of length and time. The results give important insight into the links between molecular details and surfactant phase structure which is being exploited to develop more systematic procedures for the molecular design and formulation of industrial systems.

  19. Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania major.

    PubMed

    Zarrati, Somayeh; Mahdavi, Mehdi; Tabatabaie, Fatemeh

    2016-06-01

    Leishmaniasis is a major infectious disease caused by protozoan parasites of the genus Leishmania. Despite of many efforts toward vaccine against Leishmania no effective vaccine has been approved yet. DNA vaccines can generate more powerful and broad immune responses than conventional vaccines. In order to increase immunity, the DNA vaccine has been supplemented with adjuvant. In this study a new nano-vaccine containing TSA recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as adjuvant) was designed and its immunogenicity tested on BALB/c mouse. After three intramuscular injection of nano-vaccine (100 μg), the recombinant TSA protein (20 μg) was injected subcutaneously. Finally as a challenge animals were infected by Leishmania major. After the last injection of nano-vaccine, after protein booster injection, and also after challenge, cellular immune and antibody responses were evaluated by ELISA method. The findings of this study showed the new nano-vaccine was capable of induction both cytokines secretion and specific antibody responses, but predominant Th1 immune response characterized by IFN-γ production compared to control groups. Moreover, results revealed that nano-vaccine was effective in reducing parasite burden in the spleen of Leishmania major-infected BALB/c mice. Base on results, current candidate vaccine has potency for further studies. PMID:27413316

  20. Major oil spill response coordination in the combat of spills in Bahrain waters

    SciTech Connect

    Brown, D.J.S.; James, J.D.

    1985-01-01

    On Aug. 25, 1980, without warning, a large oil slick invaded the north and west coasts of Bahrain. This serious incident was designated a national emergency, and a special high-level government committee was established immediately to handle the response procedure. This paper describes how the committee functioned with the private sector and the problems encountered and overcome. The lessons learned have stimulated interest in the proposed use of computers to aid combat operations as both a technical tool and an information service. In addition, this experience can guide those responsible for controlling response operations for future major oil spills in coastal areas. With proper planning, a highly satisfactory cooperative organization can be established between goverment and the private sector to respond effectively, economically, and with minimum environmental damage to a major oil spill affecting coastal waters and shorelines. Part of this planning is to collate and record the major available response equipment and material packages, thereby increasing the necessary state of readiness.

  1. Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

    PubMed Central

    Baek, Song-Eun; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Rho, Dae-Young; Kim, Do-Hoon; Huh, Sun

    2016-01-01

    Objective This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method. Methods Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later. Results There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups. Conclusion These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA. PMID:27081384

  2. MOLECULAR GENETICS OF THE SWINE MAJOR HISTOCOMPATIBILITY COMPLEX, THE SLA COMPLEX

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The swine major histocompatibility complex (MHC) or swine leukocyte antigen (SLA) complex is one of the most gene-dense regions in the swine genome. It consists of three major gene clusters, the SLA class I, class III and class II regions, that span ~1.1, 0.7 and 0.5 Mb, respectively, making the swi...

  3. Molecular Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib - Single Centre Experience.

    PubMed

    Pavkovic, Marica; Angelkovic, Rosica; Popova-Simjanovska, Marija; Genadieva-Stavric, Sonja; Cevreska, Lidija; Stojanovic, Aleksandar

    2015-01-01

    Introduction of tyrosine kinase inhibitors (TKI) dramatically improves the treatment and survival of the patients with chronic myeloid leukemia (CML) in the last decade. Imatinib (IM) and other TKI induce larger percentage of complete cytogenetic response (CCyR) and major molecular response (MMR). Treatment resistance to TKIs still remains an important problem in the treatment of CML. The aim of our study was to analyze the molecular response (MR) in CML patients treated with Imatinib in our institution. We have analyzed 53 CML patients (pts), 28 females and 25 males, treated with IM as a front or second line treatment. Only 15 pts were treated with IM as a front-line therapy, while 38 pts were pretreated with hydroxyurea or/and interferon. Median duration of CML was 6 years (range: 1 year- 17 years). Median duration of IM treatment was 3 years (range: 1 year-10 years). MR was analyzed in one up to 8 time points with Real Time Quantitative RT-PCR method. Forty six pts (87%) had complete hematological response and 55% of pts had MMR, 13/53(24.5%) pts had MMR at 4.0-4.5 log and 16/53(30.2%) pts had MMR at 3.0-4.0 log. MMR was not achieved in 24/53(45.3%). Our results have shown smaller percentage of patients (55%) with MMR, mostly due to the fact that larger proportion of patients (38/53) were heavily pretreated with HU or/and Interferon for a prolonged period of time, before the IM treatment. This is a major risk factor for acquisition of additional molecular and cytogenetic abnormalities responsible for IM resistance and poor treatment response. PMID:27442383

  4. A 35-kilodalton protein is a major target of the human immune response to Mycobacterium leprae.

    PubMed Central

    Triccas, J A; Roche, P W; Winter, N; Feng, C G; Butlin, C R; Britton, W J

    1996-01-01

    The control of leprosy will be facilitated by the identification of major Mycobacterium leprae-specific antigens which mirror the immune response to the organism across the leprosy spectrum. We have investigated the host response to a 35-kDa protein of M. leprae. Recombinant 35-kDa protein purified from Mycobacterium smegmatis resembled the native antigen in the formation of multimeric complexes and binding by monoclonal antibodies and sera from leprosy patients. These properties were not shared by two forms of 35-kDa protein purified from Escherichia coli. The M. smegmatis-derived 35-kDa protein stimulated a gamma interferon-secreting T-cell proliferative response in the majority of paucibacillary leprosy patients and healthy contacts of leprosy patients tested. Cellular responses to the protein in patients with multibacillary leprosy were weak or absent, consistent with hyporesponsiveness to M. leprae characteristic of this form of the disease. Almost all leprosy patients and contacts recognized the 35-kDa protein by either a T-cell proliferative or an immunoglobulin G antibody response, whereas few tuberculosis patients recognized the antigen. This specificity was confirmed in guinea pigs, with the 35-kDa protein eliciting strong delayed-type hypersensitivity in M. leprae-sensitized animals but not in those sensitized with Mycobacterium tuberculosis or Mycobacterium bovis BCG. Therefore, the M. leprae 35-kDa protein appears to be a major and relatively specific target of the human immune response to M. leprae and is a potential component of a diagnostic test to detect exposure to leprosy or a vaccine to combat the disease. PMID:8945562

  5. Molecular responses of Frankia sp. strain QA3 to naphthalene.

    PubMed

    Baker, Ethan; Tang, Yang; Chu, Feixia; Tisa, Louis S

    2015-04-01

    The Frankia-actinorhizal plant symbiosis plays a significant role in plant colonization in soils contaminated with heavy metals and toxic aromatic hydrocarbons. The molecular response of Frankia upon exposure to soil contaminants is not well understood. To address this issue, we subjected Frankia sp. strain QA3 to naphthalene stress and showed that it could grow on naphthalene as a sole carbon source. Bioinformatic analysis of the Frankia QA3 genome identified a potential operon for aromatic compound degradation as well as several ring-hydroxylating dioxygenases. Under naphthalene stress, the expression of these genes was upregulated. Proteome analysis showed a differential protein profile for cells under naphthalene stress. Several protein spots were analyzed and used to identify proteins involved in stress response, metabolism, and energy production, including a lignostilbene dioxygenase. These results provide a model for understanding the molecular response of Frankia to common soil pollutants, which may be required for survival and proliferation of the bacterium and their hosts in polluted environments. PMID:25742598

  6. Molecular responses of Frankia sp. strain QA3 to naphthalene.

    PubMed

    Baker, Ethan; Tang, Yang; Chu, Feixia; Tisa, Louis S

    2015-04-01

    The Frankia-actinorhizal plant symbiosis plays a significant role in plant colonization in soils contaminated with heavy metals and toxic aromatic hydrocarbons. The molecular response of Frankia upon exposure to soil contaminants is not well understood. To address this issue, we subjected Frankia sp. strain QA3 to naphthalene stress and showed that it could grow on naphthalene as a sole carbon source. Bioinformatic analysis of the Frankia QA3 genome identified a potential operon for aromatic compound degradation as well as several ring-hydroxylating dioxygenases. Under naphthalene stress, the expression of these genes was upregulated. Proteome analysis showed a differential protein profile for cells under naphthalene stress. Several protein spots were analyzed and used to identify proteins involved in stress response, metabolism, and energy production, including a lignostilbene dioxygenase. These results provide a model for understanding the molecular response of Frankia to common soil pollutants, which may be required for survival and proliferation of the bacterium and their hosts in polluted environments.

  7. Molecular mechanisms underlying genotype-dependent responses to dietary restriction

    PubMed Central

    Schleit, Jennifer; Johnson, Simon C.; Bennett, Christopher F.; Simko, Marissa; Trongtham, Natalie; Castanza, Anthony; Hsieh, Edward J.; Moller, Richard M.; Wasko, Brian M.; Delaney, Joe R.; Sutphin, George L.; Carr, Daniel; Murakami, Christopher J.; Tocchi, Autumn; Xian, Bo; Chen, Weiyang; Yu, Tao; Goswami, Sarani; Higgins, Sean; Holmberg, Mollie; Jeong, Ki-Soo; Kim, Jin R.; Klum, Shannon; Liao, Eric; Lin, Michael S.; Lo, Winston; Miller, Hillary; Olsen, Brady; Peng, Zhao J.; Pollard, Tom; Pradeep, Prarthana; Pruett, Dillon; Rai, Dilreet; Ros, Vanessa; Singh, Minnie; Spector, Benjamin L.; Wende, Helen Vander; An, Elroy H.; Fletcher, Marissa; Jelic, Monika; Rabinovitch, Peter S.; MacCoss, Michael J.; Han, Jing-Dong J.; Kennedy, Brian K.; Kaeberlein, Matt

    2013-01-01

    Summary Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single-gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR) which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms. PMID:23837470

  8. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

    PubMed

    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  9. Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms

    PubMed Central

    Misaki, Masaya; Suzuki, Hideo; Savitz, Jonathan; Drevets, Wayne C.; Bodurka, Jerzy

    2016-01-01

    Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD. PMID:26880358

  10. An Examination of Music and Nonmusic Majors' Response to Selected Excerpts from Stravinsky's Le Sacre du Printemps.

    ERIC Educational Resources Information Center

    Misenhelter, Dale; Price Harry E.

    2001-01-01

    Presents a study that explored the relationship between music and nonmusic majors' real-time responses to a piece of twentieth century music. Explains that the undergraduate nonmusic majors and undergraduate and graduate music majors manipulated a Continuous Response Digital Interface dial. (CMK)

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

    ERIC Educational Resources Information Center

    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)…

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

    ERIC Educational Resources Information Center

    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,…

  13. Antioxidant-enriched enteral nutrition and immuno-inflammatory response after major gastrointestinal tract surgery.

    PubMed

    van Stijn, Mireille F M; Boelens, Petra G; Richir, Milan C; Ligthart-Melis, Gerdien C; Twisk, Jos W R; Diks, Jeroen; Houdijk, Alexander P J; van Leeuwen, Paul A M

    2010-02-01

    Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

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

    PubMed

    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.

  15. Valence and agency influence striatal response to feedback in patients with major depressive disorder

    PubMed Central

    Späti, Jakub; Chumbley, Justin; Doerig, Nadja; Brakowski, Janis; Holtforth, Martin Grosse; Seifritz, Erich; Spinelli, Simona

    2015-01-01

    Background Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one’s own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses. Methods Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls. Results We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA – EA losses in patients with MDD compared with healthy controls. Limitations Depressed patients with comorbid anxiety disorder were included. Conclusion These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness. PMID:26107160

  16. Molecular Architecture of the Major Histocompatibility Complex Class I-binding Site of Ly49 Natural Killer Cell Receptors*

    PubMed Central

    Deng, Lu; Cho, Sangwoo; Malchiodi, Emilio L.; Kerzic, Melissa C.; Dam, Julie; Mariuzza, Roy A.

    2008-01-01

    Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2Kb complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally. PMID:18426793

  17. Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors

    SciTech Connect

    Deng,L.; Cho, S.; Malchiodi, E.; Kerzic, M.; Dam, J.; Mariuzza, R.

    2008-01-01

    Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2Kb complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.

  18. Gamma-glutamylcysteine and thiosulfate are the major low-molecular-weight thiols in halobacteria

    NASA Technical Reports Server (NTRS)

    Newton, Gerald L.; Javor, Barbara

    1985-01-01

    Six representative species of extremely halophilic bacteria were found to contain approximately millimolar concentrations of gamma-glutamylcysteine in the absence of significant glutathione. Thiosulfate also accumulated in the halobacteria, apparently as a major product of cysteine oxidation.

  19. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder.

    PubMed

    Szczepanik, Joanna; Nugent, Allison C; Drevets, Wayne C; Khanna, Ashish; Zarate, Carlos A; Furey, Maura L

    2016-08-30

    The muscarinic antagonist scopolamine produces rapid antidepressant effects in individuals with major depressive disorder (MDD). In healthy subjects, manipulation of acetyl-cholinergic transmission modulates attention in a stimulus-dependent manner. This study tested the hypothesis that baseline amygdalar activity in response to emotional stimuli correlates with antidepressant treatment response to scopolamine and could thus potentially predict treatment outcome. MDD patients and healthy controls performed an attention shifting task involving emotional faces while undergoing functional magnetic resonance imaging (fMRI). We found that blood oxygenation level dependent (BOLD) signal in the amygdala acquired while MDD patients processed sad face stimuli correlated positively with antidepressant response to scopolamine. Amygdalar response to sad faces in MDD patients who did not respond to scopolamine did not differ from that of healthy controls. This suggests that the pre-treatment task elicited amygdalar activity that may constitute a biomarker of antidepressant treatment response to scopolamine. Furthermore, in MDD patients who responded to scopolamine, we observed a post-scopolamine stimulus processing shift towards a pattern demonstrated by healthy controls, indicating a change in stimulus-dependent neural response potentially driven by attenuated cholinergic activity in the amygdala. PMID:27366831

  20. Topology and static response of interaction networks in molecular biology.

    PubMed

    Radulescu, Ovidiu; Lagarrigue, Sandrine; Siegel, Anne; Veber, Philippe; Le Borgne, Michel

    2006-02-22

    We introduce a mathematical framework describing static response of networks occurring in molecular biology. This formalism has many similarities with the Laplace-Kirchhoff equations for electrical networks. We introduce the concept of graph boundary and we show how the response of the biological networks to external perturbations can be related to the Dirichlet or Neumann problems for the corresponding equations on the interaction graph. Solutions to these two problems are given in terms of path moduli (measuring path rigidity with respect to the propagation of interaction along the graph). Path moduli are related to loop products in the interaction graph via generalized Mason-Coates formulae. We apply our results to two specific biological examples: the lactose operon and the genetic regulation of lipogenesis. Our applications show consistency with experimental results and in the case of lipogenesis check some hypothesis on the behaviour of hepatic fatty acids on fasting. PMID:16849230

  1. Topology and static response of interaction networks in molecular biology

    PubMed Central

    Radulescu, Ovidiu; Lagarrigue, Sandrine; Siegel, Anne; Veber, Philippe; Le Borgne, Michel

    2005-01-01

    We introduce a mathematical framework describing static response of networks occurring in molecular biology. This formalism has many similarities with the Laplace–Kirchhoff equations for electrical networks. We introduce the concept of graph boundary and we show how the response of the biological networks to external perturbations can be related to the Dirichlet or Neumann problems for the corresponding equations on the interaction graph. Solutions to these two problems are given in terms of path moduli (measuring path rigidity with respect to the propagation of interaction along the graph). Path moduli are related to loop products in the interaction graph via generalized Mason–Coates formulae. We apply our results to two specific biological examples: the lactose operon and the genetic regulation of lipogenesis. Our applications show consistency with experimental results and in the case of lipogenesis check some hypothesis on the behaviour of hepatic fatty acids on fasting. PMID:16849230

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

    PubMed

    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

  3. Sympathetic skin response following painful electrical stimulation is increased in major depression.

    PubMed

    Boettger, Michael Karl; Greiner, Wolf; Rachow, Tobias; Brühl, Christiane; Bär, Karl-Jürgen

    2010-04-01

    Patients with major depressive disorder have repeatedly been described to exhibit increased thresholds upon experimentally applied pain stimuli to the skin as compared to respective controls. Since the sensory-discriminative component of stimulus perception, e.g. for warmth, cold and vibration, appears to be unaltered in depression, higher central nervous centres have been assumed to cause this phenomenon. To date, hardly any attention has been paid to the efferent components of the noxious reflex loop. Here, we aimed to assess the autonomic reaction upon a painful stimulus and to examine whether this is likewise reduced in major depression. For this purpose, sympathetic skin response was obtained from 22 patients with major depression and 20 matched controls. To induce sympathetic skin responses, we applied either noxious electrical stimuli (12 and 18 mA) or innocuous acoustic stimuli (85 dB SPL). Pain intensity was rated using a numeric analogue scale. In contrast to our a priori hypothesis patients showed shorter latencies and higher amplitudes of skin potentials upon noxious stimulation, i.e. a stronger sympathetic response. Intriguingly, the noxious stimuli were still perceived less painful in the patient group. Pain perception weakly correlated with disease severity. From these data, we conclude that despite the diminished pain perception, the autonomic reflex loop following noxious stimulation is not affected in patients with major depressive disorder, and that the increase in sympathetic outflow is not directly related to the perceived pain as in controls, but might rather be attributed to the autonomic dysfunction known for the disease.

  4. Cellular stress response pathways and ageing: intricate molecular relationships

    PubMed Central

    Kourtis, Nikos; Tavernarakis, Nektarios

    2011-01-01

    Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, senescent decline and ageing is broadly influenced by genetic and extrinsic factors. Numerous gene mutations and treatments have been shown to extend the lifespan of diverse organisms ranging from the unicellular Saccharomyces cerevisiae to primates. It is becoming increasingly apparent that most such interventions ultimately interface with cellular stress response mechanisms, suggesting that longevity is intimately related to the ability of the organism to effectively cope with both intrinsic and extrinsic stress. Here, we survey the molecular mechanisms that link ageing to main stress response pathways, and mediate age-related changes in the effectiveness of the response to stress. We also discuss how each pathway contributes to modulate the ageing process. A better understanding of the dynamics and reciprocal interplay between stress responses and ageing is critical for the development of novel therapeutic strategies that exploit endogenous stress combat pathways against age-associated pathologies. PMID:21587205

  5. Differential Regulation of the Interleukin-12 Receptor during the Innate Immune Response to Leishmania major

    PubMed Central

    Jones, Douglas; Elloso, M. Merle; Showe, Louise; Williams, Donna; Trinchieri, Giorgio; Scott, Phillip

    1998-01-01

    Previous studies have shown the central role of interleukin 12 (IL-12) in the development of resistance to Leishmania major infection in C3H mice. We now show that during the innate immune response the lymph node cells of L. major-infected C3H mice upregulate the IL-12 receptor on CD4+, CD8+, and B220+ cells. An increase in the ability of the lymph node cells to bind IL-12 correlates with 9.3- and 4.6-fold increases in the mRNA expression levels of the IL-12Rβ1 and -β2 subunits, respectively. In contrast, BALB/c mice, which are susceptible to L. major infection, have no increase in the ability of the lymph node cells to bind IL-12 and correspondingly smaller increases in the mRNA expression levels of the IL-12Rβ1 and -β2 subunits of 2- and 1.5-fold, respectively. Neutralizing IL-4 and the administration of exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while the neutralization of IL-12 in C3H mice blocks increased IL-12 receptor expression. These experiments reveal an important role for the regulation of the IL-12 receptor during the innate immune response after infection of mice with a pathogen. PMID:9673267

  6. PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder.

    PubMed

    Schuhmacher, Anna; Mössner, Rainald; Höfels, Susanne; Pfeiffer, Ute; Guttenthaler, Vera; Wagner, Michael; Schwab, Sibylle G; Maier, Wolfgang; Zobel, Astrid

    2011-03-01

    Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

  7. The Hasford Score May Predict Molecular Response in Chronic Myeloid Leukemia Patients: A Single Institution Experience

    PubMed Central

    Jaźwiec, Bożena; Haus, Olga; Urbaniak-Kujda, Donata; Kapelko-Słowik, Katarzyna; Wróbel, Tomasz; Lonc, Tomasz; Sawicki, Mateusz; Mędraś, Ewa; Kaczmar-Dybko, Agnieszka; Kuliczkowski, Kazimierz

    2016-01-01

    The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients.

  8. Passive Immunotherapy for Retroviral Disease: Influence of Major Histocompatibility Complex Type and T-Cell Responsiveness

    NASA Astrophysics Data System (ADS)

    Hasenkrug, Kim J.; Brooks, Diane M.; Chesebro, Bruce

    1995-11-01

    Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4^+ and CD8^+ T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed.

  9. Heterogeneity of Wild Leishmania major Isolates in Experimental Murine Pathogenicity and Specific Immune Response

    PubMed Central

    Kébaïer, C.; Louzir, H.; Chenik, M.; Salah, A. Ben; Dellagi, K.

    2001-01-01

    Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 × 106 amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-γ) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-γ in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host. PMID:11447167

  10. Molecular Genetic Diversity of Major Indian Rice Cultivars over Decadal Periods

    PubMed Central

    Deborah, Dondapati Annekitty; Vipparla, Abhilash; Anuradha, Ghanta; Siddiq, Ebrahimali Abubacker; Vemireddy, Lakshminarayana Reddy

    2013-01-01

    Genetic diversity in representative sets of high yielding varieties of rice released in India between 1970 and 2010 was studied at molecular level employing hypervariable microsatellite markers. Of 64 rice SSR primer pairs studied, 52 showed polymorphism, when screened in 100 rice genotypes. A total of 184 alleles was identified averaging 3.63 alleles per locus. Cluster analysis clearly grouped the 100 genotypes into their respective decadal periods i.e., 1970s, 1980s, 1990s and 2000s. The trend of diversity over the decadal periods estimated based on the number of alleles (Na), allelic richness (Rs), Nei’s genetic diversity index (He), observed heterozygosity (Ho) and polymorphism information content (PIC) revealed increase of diversity over the periods in year of releasewise and longevitywise classification of rice varieties. Analysis of molecular variance (AMOVA) suggested more variation in within the decadal periods than among the decades. Pairwise comparison of population differentiation (Fst) among decadal periods showed significant difference between all the pairs except a few. Analysis of trends of appearing and disappearing alleles over decadal periods showed an increase in the appearance of alleles and decrease in disappearance in both the categories of varieties. It was obvious from the present findings, that genetic diversity was progressively on the rise in the varieties released during the decadal periods, between 1970s and 2000s. PMID:23805204

  11. Molecular Factors in Dendritic Cell Responses to Adsorbed Glycoconjugates

    PubMed Central

    Hotaling, Nathan A.; Cummings, Richard D.; Ratner, Daniel M.; Babensee, Julia E.

    2014-01-01

    Carbohydrates and glycoconjugates have been shown to exert pro-inflammatory effects on the dendritic cell (DC), supporting pathogen-induced innate immunity and antigen processing, as well as immunosuppressive effects in the tolerance to self-proteins. Additionally, the innate inflammatory response to implanted biomaterials has been hypothesized to be mediated by inflammatory cells interacting with adsorbed proteins, many of which are glycosylated. However, the molecular factors relevant for surface displayed glycoconjugate modulation of DC phenotype are unknown. Thus, in this study, a model system was developed to establish the role of glycan composition, density, and carrier cationization state on DC response. Thiol modified glycans were covalently bound to a model protein carrier, maleimide functionalized bovine serum albumin (BSA), and the number of glycans per BSA modulated. Additionally, the carrier isoelectric point was scaled from a pI of ~4.0 to ~10.0 using ethylenediamine (EDA). The DC response to the neoglycoconjugates adsorbed to wells of a 384 well plate was determined via a high throughput assay. The underlying trends in DC phenotype in relation to conjugate properties were elucidated via multivariate general linear models. It was found that glycoconjugates with more than 20 glycans per carrier had the greatest impact on the pro-inflammatory response from DCs, followed by conjugates having an isoelectric point above 9.5. Surfaces displaying terminal α1–2 linked mannose structures were able to increase the inflammatory DC response to a greater extent than did any other terminal glycan structure. The results herein can be applied to inform the design of the next generation of combination products and biomaterials for use in future vaccines and implanted materials. PMID:24746228

  12. Early Symptom Improvement as a Predictor of Response to Extended Release Quetiapine in Major Depressive Disorder

    PubMed Central

    McIntyre, Roger S.; Gorwood, Philip; Thase, Michael E.; Liss, Charlie; Desai, Dhaval; Chen, Ji; Bauer, Michael

    2015-01-01

    Abstract The aim of this post-hoc analysis was to determine whether early symptom improvement with extended release quetiapine (quetiapine XR) may predict treatment outcome in patients with major depressive disorder. Data were from 6, double-blind, placebo-controlled studies of quetiapine XR (2 fixed-dose and 2 flexible-dose monotherapy and 2 adjunct studies) in adult patients with major depressive disorder. Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression-Severity Score (CGI-S) were assessed at baseline, weeks 2, 4, and 6. Hamilton Rating Scale for Depression (HAM-D) was assessed at baseline and week 6. The MADRS improvement at week 2 (15%, 20%, 25%, 30%) was used to predict response and remission, based on MADRS (50% improvement; total score ≤ 12) or HAM-D (50% improvement; total score ≤ 7). The CGI-S improvement (1 point) at week 2 was used to predict final outcome (CGI-S score ≤ 2). The predictive value for early improvement with quetiapine XR was found to be “very strong” (Yule’s Q coefficient, a combined measure of sensitivity and specificity) using 30% MADRS improvement as the threshold. This was relatively comparable for response and remission and for fixed-dose, flexible-dose, and adjunct studies. This was also observed for placebo. Exceptions were: adjunct studies (where predictivity was lower for ongoing antidepressant/placebo), and for remission (predictivity for remission appeared lower than for response with placebo). In conclusion, outcome at week 6 with quetiapine XR for a major depressive episode could be predicted by 30% improvement after 2 weeks, a finding that could give doctors confidence to continue treatment and may facilitate adherence in patients. PMID:26474010

  13. WRKY Transcription Factors: Molecular Regulation and Stress Responses in Plants

    PubMed Central

    Phukan, Ujjal J.; Jeena, Gajendra S.; Shukla, Rakesh K.

    2016-01-01

    Plants in their natural habitat have to face multiple stresses simultaneously. Evolutionary adaptation of developmental, physiological, and biochemical parameters give advantage over a single window of stress but not multiple. On the other hand transcription factors like WRKY can regulate diverse responses through a complicated network of genes. So molecular orchestration of WRKYs in plant may provide the most anticipated outcome of simultaneous multiple responses. Activation or repression through W-box and W-box like sequences is regulated at transcriptional, translational, and domain level. Because of the tight regulation involved in specific recognition and binding of WRKYs to downstream promoters, they have become promising candidate for crop improvement. Epigenetic, retrograde and proteasome mediated regulation enable WRKYs to attain the dynamic cellular homeostatic reprograming. Overexpression of several WRKYs face the paradox of having several beneficial affects but with some unwanted traits. These overexpression-associated undesirable phenotypes need to be identified and removed for proper growth, development and yeild. Taken together, we have highlighted the diverse regulation and multiple stress response of WRKYs in plants along with the future prospects in this field of research. PMID:27375634

  14. Plant adaptation to low atmospheric pressures: potential molecular responses

    NASA Technical Reports Server (NTRS)

    Ferl, Robert J.; Schuerger, Andrew C.; Paul, Anna-Lisa; Gurley, William B.; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

  15. Plant adaptation to low atmospheric pressures: potential molecular responses.

    PubMed

    Ferl, Robert J; Schuerger, Andrew C; Paul, Anna-Lisa; Gurley, William B; Corey, Kenneth; Bucklin, Ray

    2002-01-01

    There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments. PMID:11987308

  16. U.S. Geological Survey disaster response and the International Charter for space and major disasters

    USGS Publications Warehouse

    Stryker, Timothy S.; Jones, Brenda K.

    2010-01-01

    In 1999, an international consortium of space agencies conceived and approved a mechanism to provide satellite information in support of worldwide disaster relief. This group came to be known as the 'International Charter?Space and Major Disasters' and has become an important resource for the use of satellite data to evaluate and provide support for response to natural and man-made disasters. From the Charter's formative days in 1999, its membership has grown to 10 space organizations managing more than 20 earth-observing satellites.

  17. Performance indicators for initial regional medical response to major incidents: a possible quality control tool

    PubMed Central

    2012-01-01

    Background Timely decisions concerning mobilization and allocation of resources and distribution of casualties are crucial in medical management of major incidents. The aim of this study was to evaluate documented initial regional medical responses to major incidents by applying a set of 11 measurable performance indicators for regional medical command and control and test the feasibility of the indicators. Methods Retrospective data were collected from documentation from regional medical command and control at major incidents that occurred in two Swedish County Councils. Each incident was assigned to one of nine different categories and 11 measurable performance indicators for initial regional medical command and control were systematically applied. Two-way analysis of variance with one observation per cell was used for statistical analysis and the post hoc Tukey test was used for pairwise comparisons. Results The set of indicators for regional medical command and control could be applied in 102 of the130 major incidents (78%), but 36 incidents had to be excluded due to incomplete documentation. The indicators were not applicable as a set for 28 incidents (21.5%) due to different characteristics and time frames. Based on the indicators studied in 66 major incidents, the results demonstrate that the regional medical management performed according to the standard in the early phases (1–10 min after alert), but there were weaknesses in the secondary phase (10–30 min after alert). The significantly lowest scores were found for Indicator 8 (formulate general guidelines for response) and Indicator 10 (decide whether or not resources in own organization are adequate). Conclusions Measurable performance indicators for regional medical command and control can be applied to incidents that directly or indirectly involve casualties provided there is sufficient documentation available. Measurable performance indicators can enhance follow- up and be used as a structured

  18. Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

    PubMed

    Pettai, Kristi; Milani, Lili; Tammiste, Anu; Võsa, Urmo; Kolde, Raivo; Eller, Triin; Nutt, David; Metspalu, Andres; Maron, Eduard

    2016-09-01

    The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further

  19. Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

    PubMed Central

    Dong, C; Maestre-Mesa, J; Licinio, J

    2009-01-01

    There are clinical parallels between the nature and course of depressive symptoms in major depressive disorder (MDD) and those of inflammatory disorders. However, the characterization of a possible immune system dysregulation in MDD has been challenging. Emerging data support the role of T-cell dysfunction. Here we report the association of MDD and antidepressant response to genes important in the modulation of the hypothalamic-pituitary-adrenal axis and immune functions in Mexican Americans with major depression. Specifically, single nucleotide polymorphisms (SNPs) in two genes critical for T-cell function are associated with susceptibility to MDD: PSMB4 (proteasome β4 subunit), important for antigen processing, and TBX21 (T bet), critical for differentiation. Our analyses revealed a significant combined allele dose-effect: individuals who had one, two and three risk alleles were 2.3, 3.2 and 9.8 times more likely to have the diagnosis of MDD, respectively. We found associations of several SNPs and antidepressant response; those genes support the role of T cell (CD3E, PRKCH, PSMD9 and STAT3) and hypothalamic-pituitary-adrenal axis (UCN3) functions in treatment response. We also describe in MDD increased levels of CXCL10/IP-10, which decreased in response to antidepressants. This further suggests predominance of type 1 T-cell activity in MDD. T-cell function variations that we describe here may account for 47.8% of the attributable risk in Mexican Americans with moderate MDD. Immune function genes are highly variable; therefore, different genes might be implicated in distinct population groups. PMID:18504423

  20. Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

    PubMed

    Pettai, Kristi; Milani, Lili; Tammiste, Anu; Võsa, Urmo; Kolde, Raivo; Eller, Triin; Nutt, David; Metspalu, Andres; Maron, Eduard

    2016-09-01

    The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further

  1. Molecular response of Escherichia coli adhering onto nanoscale topography

    PubMed Central

    2012-01-01

    Bacterial adhesion onto abiotic surfaces is an important issue in biology and medicine since understanding the bases of such interaction represents a crucial aspect in the design of safe implant devices with intrinsic antibacterial characteristics. In this framework, we investigated the effects of nanostructured metal substrates on Escherichia coli adhesion and adaptation in order to understand the bio-molecular dynamics ruling the interactions at the interface. In particular, we show how highly controlled nanostructured gold substrates impact the bacterial behavior in terms of morphological changes and lead to modifications in the expression profile of several genes, which are crucially involved in the stress response and fimbrial synthesis. These results mainly demonstrate that E. coli cells are able to sense even slight changes in surface nanotopography and to actively respond by activating stress-related pathways. At the same time, our findings highlight the possibility of designing nanoengineered substrates able to trigger specific bio-molecular effects, thus opening the perspective of smartly tuning bacterial behavior by biomaterial design. PMID:23078758

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

    PubMed

    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.

  3. A molecular simulation study on salt response of polyelectrolyte complexes

    NASA Astrophysics Data System (ADS)

    Antila, Hanne; van Tassel, Paul; Sammalkorpi, Maria

    2015-03-01

    In aqueous solutions, oppositely charged polymers, polyelectrolytes (PEs) form complexes which are known to be sensitive to added salt with responses ranging from shrinking to full destabilization of the complex. As a specific application of PE complexes, the complex formation of DNA with polycations has been demonstrated to be an effective means of transfecting genetic material in gene therapy. We use all-atom molecular dynamics and coarse-grained Monte Carlo simulations to investigate the effect of excess salt on DNA-polycation complex stability. The detailed all-atom simulations demonstrate the mechanism of polycation and ion species specific salt-driven dissociation involving charge reversal. More generally, other possible mechanisms of salt driven dissociation exist as well. The coarse grained approach, which describes the PE complex as oppositely charged, rigid rods and ions as hard spheres, provides a more complete understanding of PE interactions in salt, and suggests possible mechanisms leading to repulsion between the oppositely charged polyelectrolytes.

  4. Molecular Dynamics Simulation of Dynamic Response of Beryllium

    NASA Astrophysics Data System (ADS)

    Thompson, Aidan P.; Lane, J. Matthew D.; Baskes, Michael I.; Desjarlais, Michael P.

    2009-06-01

    The response of beryllium to dynamic loading has been extensively studied, both experimentally and theoretically, due to its importance in several technological areas. Compared to other metals, it is quite challenging to accurately represent the various anomalous behaviors of beryllium using classical interatomic potentials. The spherically-symmetric EAM potential can not reproduce the observed c/a ratio for α-Be under ambient conditions, which is significantly smaller than the ideal HCP value. The directional-dependence of the MEAM potential overcomes this problem, but introduces additional complexity. We will compare predictions of these classical potentials to experimental measurements of beryllium at ambient conditions, and also to theoretical calculations at high temperatures and pressures. Finally, we will present initial results from non-equilibrium molecular dynamics simulations of beryllium under dynamic loading. This work is supported by the Laboratory Directed Research and Development program at Sandia National Laboratories.

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

    PubMed Central

    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. Global Temperature Response to the Major Volcanic Eruptions in Multiple Reanalysis Datasets

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L. J.; Mitchell, D.; Anstey, J.

    2015-12-01

    Global temperature response to the eruptions of Mount Agung in 1963, El Chichón in 1982 and Mount Pinatubo in 1991 is investigated using nine reanalysis datasets (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 datasets) and 1958-2001 (for four reanalysis datasets), 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. In response to the Mount Pinatubo eruption, most reanalysis datasets show strong warming signals (up to 2-3 K for one-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 datasets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis datasets.

  7. The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

    PubMed

    Caudill, Marissa M; Hunter, Aimee M; Cook, Ian A; Leuchter, Andrew F

    2015-10-01

    Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.

  8. The alignment between phenotypic plasticity, the major axis of genetic variation and the response to selection

    PubMed Central

    Lind, Martin I.; Yarlett, Kylie; Reger, Julia; Carter, Mauricio J.; Beckerman, Andrew P.

    2015-01-01

    Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments. PMID:26423845

  9. Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils.

    PubMed

    Rasmussen-Torvik, Laura J; McAlpine, Donna D

    2007-01-01

    This article examines evidence for the potential benefit of genetic testing for SSRI response, as well as potential ethical and practical implications of the implementation of this test into standard psychiatric practice. We reviewed three areas of the literature: the burden of treatment-resistant and treatment-intolerant major depressive disorders, the evidence for the value of genetic testing to predict drug response, and the ethical and practical issues of genetic testing in usual care. Treatment resistance and treatment intolerance are common for persons treated with selective serotonin reuptake inhibitors (SSRIs) and are associated with both financial and quality-of-life costs. There is strong evidence from association studies that some polymorphisms are associated with SSRI response. However, no randomized trials have yet tested the efficacy of genetic tests to improve outcome in those with treatment resistance or treatment intolerance to SSRIs. Given the nonspecific nature of the test proposed, several ethical concerns are also involved with administering the genetic tests to patients. A randomized trial comparing response in those treated with standard psychiatric care and in those treated with psychiatric care tailored as a result of genetic test results should be completed before the implementation of these tests can be considered. Additionally, the ethical and practical questions concerning the tests must be addressed now, so that the potential impact of these tests on patient care can be well understood prior to adoption in standard practice.

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

    PubMed Central

    van der Meer, Esther; van Oers, Kees

    2015-01-01

    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. PMID:26011633

  11. A major thyroid hormone response element in the third intron of the rat growth hormone gene.

    PubMed Central

    Sap, J; de Magistris, L; Stunnenberg, H; Vennström, B

    1990-01-01

    The rat growth hormone (RGH) gene constitutes a well-documented model system for the direct regulation of transcription by thyroid hormones. In order to analyse its interaction with sequences in the RGH gene, we have overproduced the thyroid hormone receptor-alpha (c-erbA) protein using a vaccinia virus expression system. The expressed protein bound T3 and DNA-cellulose with expected affinities, and the major binding site for the receptor protein was found to be located in the third intron of the RGH gene. This site displayed significantly higher affinity for the receptor protein than a previously described thyroid hormone response element (TRE) in the promoter of this gene, and also conferred stronger hormone responsiveness in vivo to a heterologous promoter. The data suggest that this novel TRE plays a major role in the regulation of rat growth hormone gene expression by thyroid hormones. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2155782

  12. A Global Investigation of the Bacillus subtilis Iron-Sparing Response Identifies Major Changes in Metabolism

    PubMed Central

    Smaldone, Gregory T.; Revelles, Olga; Gaballa, Ahmed; Sauer, Uwe; Antelmann, Haike

    2012-01-01

    The Bacillus subtilis ferric uptake regulator (Fur) protein is the major sensor of cellular iron status. When iron is limiting for growth, derepression of the Fur regulon increases the cellular capacity for iron uptake and mobilizes an iron-sparing response mediated in large part by a small noncoding RNA named FsrA. FsrA functions, in collaboration with three small basic proteins (FbpABC), to repress many “low-priority” iron-containing enzymes. We have used transcriptome analyses to gain insights into the scope of the iron-sparing response and to define subsets of genes dependent for their repression on FsrA, FbpAB, and/or FbpC. Enzymes of the tricarboxylic acid (TCA) cycle, including aconitase and succinate dehydrogenase (SDH), are major targets of FsrA-mediated repression, and as a consequence, flux through this pathway is significantly decreased in a fur mutant. FsrA also represses the DctP dicarboxylate permease and the iron-sulfur-containing enzyme glutamate synthase (GltAB), which serves as a central link between carbon and nitrogen metabolism. Allele-specific suppression analysis was used to document a direct RNA-RNA interaction between the FsrA small RNA (sRNA) and the gltAB leader region. We further demonstrated that distinct regions of FsrA are required for the translational repression of the GltAB and SDH enzyme complexes. PMID:22389480

  13. Cathepsin L is crucial for a Th1-type immune response during Leishmania major infection.

    PubMed

    Onishi, Kotaro; Li, Yang; Ishii, Kazunari; Hisaeda, Hajime; Tang, Lijun; Duan, Xuefeng; Dainichi, Teruki; Maekawa, Yoichi; Katunuma, Nobuhiko; Himeno, Kunisuke

    2004-04-01

    Prior to the activation of CD4+ T cells, exogenous proteins are digested by endo/lysosomal enzymes in antigen-presenting cells (APCs) to produce antigenic peptides that are presented on MHC class II molecules. In the studies described here, the functional significance of cathepsin L for antigen processing and Th1/Th2 differentiation in experimental leishmaniasis was investigated. We first demonstrated that cathepsin L is one of the candidates for endo/lysosomal enzymes in the processing of soluble Leishmania antigen (SLA) by using CLIK148, a specific inhibitor of cathepsin L. Treatment of BALB/c or DBA/2 mice with CLIK148 exacerbated the disease by enhancing an SLA-specific Th2-type response such as IL-4 production. CLIK148 did not exert any direct influence on Leishmania major promastigotes themselves or on the course of L. major infection in SCID mice. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APCs, resulting in the potentiation of Th2-type immune responses and thus leading to exacerbation of the disease. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.

  14. Molecular characterization of major allergens Ara h 1, 2, 3 in peanut seed.

    PubMed

    Jiang, Shengjuan; Wang, Songhua; Sun, Yujun; Zhou, Zhengyi; Wang, Guiqin

    2011-06-01

    Peanut is among the most commonly used dietary seeds, but peanut allergens, especially Ara h 1 (Arachis hypogaea allergy 1), 2 and 3, can cause severe IgE-mediated reactions. In this study, the molecular characterization and expression pattern of three allergens in peanut LUHUA 8, the representative of the cultivated lines in China, are reported. In situ hybridization and real time PCR analysis revealed high expression levels and different tissue expression patterns of the three allergens, which might be connected with many aspects, such as the strong conservation of intron phase of the allergen genes, the low energy of the mRNA's regions, and the complicated post-translational modifications. Furthermore, the different sequences between the cloned allergens and the reported sequences previously involved the charged amino acids especially in IgE epitopes, which might alter specific physicochemical and physiological properties, and thus influence the immunity of the allergens. The identification of the specific features of the allergen genes would be of considerable importance to the basic understanding of the specific characteristics of peanut seed allergens.

  15. A broad molecular phylogeny of ciliates: identification of major evolutionary trends and radiations within the phylum.

    PubMed Central

    Baroin-Tourancheau, A; Delgado, P; Perasso, R; Adoutte, A

    1992-01-01

    The cellular architecture of ciliates is one of the most complex known within eukaryotes. Detailed systematic schemes have thus been constructed through extensive comparative morphological and ultrastructural analysis of the ciliature and of its internal cytoskeletal derivatives (the infraciliature), as well as of the architecture of the oral apparatus. In recent years, a consensus was reached in which the phylum was divided in eight classes as defined by Lynn and Corliss [Lynn, D. H. & Corliss, J. O. (1991) in Microscopic Anatomy of Invertebrates: Protozoa (Wiley-Liss, New York), Vol. 1, pp. 333-467]. By comparing partial sequences of the large subunit rRNA molecule, and by using both distance-matrix and maximum-parsimony-tree construction methods (checked by boot-strapping), we examine the phylogenetic relationships of 22 species belonging to seven of these eight classes. At low taxonomic levels, the traditional grouping of the species is generally confirmed. At higher taxonomic levels, the branching pattern of these seven classes is resolved in several deeply separated major branches. Surprisingly, the first emerging one contains the heterotrichs and is strongly associated with a karyorelictid but deeply separated from hypotrichs. The litostomes, the oligohymenophorans, and the hypotrichs separate later in a bush-like topology hindering the resolution of their order of diversification. These results show a much more ancient origin of heterotrichs than was classically assumed, indicating that asymmetric, abundantly ciliated oral apparatuses do not correspond to "highly evolved" traits as previously thought. They also suggest the occurrence of a major radiative explosion in the evolutionary history of the ciliates, yielding five of the eight classes of the phylum. These classes appear to differ essentially according to the cytoskeletal architecture used to shape and sustain the cellular cortex (a process of essential adaptative and morphogenetic importance in

  16. Global temperature response to the major volcanic eruptions in multiple reanalysis datasets

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L.; Mitchell, D.; Anstey, J.

    2015-05-01

    Global temperature response to the eruptions of Mount Agung in 1963, El Chichón in 1982 and Mount Pinatubo in 1991 is investigated using nine reanalysis datasets (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 datasets) and 1958-2001 (for four reanalysis datasets), 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. In response to the Mount Pinatubo eruption, most reanalysis datasets show strong warming signals (up to 2-3 K for one-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. The response to three other smaller-scale eruptions in the 1960s and 1970s is also investigated. Comparison of the results from several different reanalysis datasets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis datasets.

  17. Dissociable cortico-striatal connectivity abnormalities in major depression in response to monetary gains and penalties

    PubMed Central

    Admon, Roee; Nickerson, Lisa D.; Dillon, Daniel G.; Holmes, Avram J.; Bogdan, Ryan; Kumar, Poornima; Dougherty, Darin D.; Iosifescu, Dan V.; Mischoulon, David; Fava, Maurizio; Pizzagalli, Diego A.

    2014-01-01

    Background Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored. Methods In this study 26 unmedicated adults with MDD and 29 matched healthy controls completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psycho-physiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e., monetary gains and penalties). Results Relative to controls, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC sub-region in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with more symptoms improvement 12 weeks later. Conclusions These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action-outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD. PMID:25055809

  18. Molecular response of liver sinusoidal endothelial cells on hydrogels.

    PubMed

    Bartneck, Matthias; Topuz, Fuat; Tag, Carmen Gabriele; Sauer-Lehnen, Sibille; Warzecha, Klaudia Theresa; Trautwein, Christian; Weiskirchen, Ralf; Tacke, Frank

    2015-06-01

    There is a high demand for the isolation of primary endothelial cells for biomaterial endotheliazation studies, tissue engineering, and artificial organ development. Further, biomarkers for monitoring the response of endothelial cells in biomaterials science are required. We systematically compared two strategies for isolating liver sinusoidal endothelial cells (LSEC) from mouse liver. We demonstrate that fluorescence-activated cell sorting results in a considerably higher purity (~97%) compared to magnetic-assisted cell sorting (~80%), but is associated with a lower yield and recovery rate. Cell repellent polyethylene glycol (PEG) substrates affected the morphology of primary LSEC in culture and significantly downregulated the intracellular adhesion molecule (ICAM) and upregulated the vascular cell adhesion molecule (VCAM). This molecular response could partially be reverted by further modification with arginylglycylaspartic acid (RGD). Thus, usage of PEGylated materials may reduce, while applying RGD may support endotheliazation of materials, and we could relate LSEC attachment to their expression of ICAM and VCAM mRNA, suggesting their usage as biomarkers for endothelialization.

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

    PubMed

    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. PMID:22063648

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:23372772

  2. Molecular Epidemiology of Clostridium difficile Infection in a Major Chinese Hospital: an Underrecognized Problem in Asia?

    PubMed Central

    Marriott, Clare; Liu, Wen En; Jian, Zi Juan; Gao, Qian; Ling, Thomas Kin Wah; Chow, Viola; So, Erica; Chan, Raphael; Hardy, Katie; Xu, Li; Manzoor, Susan

    2013-01-01

    Clostridium difficile infection is almost unrecognized in mainland China. We have undertaken a study in a large Chinese teaching hospital in Changsha, Hunan, China, to identify cases of C. difficile, record patient characteristics, and define the molecular epidemiology with respect to ribotype distribution and cross-infection. Between April 2009 and February 2010, we examined fecal samples from 70 hospitalized patients with diarrhea who were receiving or had received antibiotics within the previous 6 weeks. Clinical information was collected and the samples were cultured for C. difficile retrospectively. Isolates were ribotyped, and multiple-locus variable-number tandem-repeat assay (MLVA) subtyping was performed on clusters of the same ribotype. The mean age of patients from whom C. difficile was cultured was 58 years, with only 4/21 patients aged >65 years. All patients, with a single exception, had received a third-generation cephalosporin and/or a quinolone antibiotic. Twenty-one isolates of C. difficile were recovered, and seven different ribotypes were identified, the dominant types being 017 (48%), 046 (14%), and 012 (14%). We identified two clusters of cross-infection with indistinguishable isolates of ribotype 017, with evidence of spread both within and between wards. We have identified C. difficile as a possibly significant problem, with cross-infection and a distinct ribotype distribution, in a large Chinese hospital. C. difficile may be underrecognized in China, and further epidemiological studies across the country together with the introduction of routine diagnostic testing are needed to ascertain the size of this potentially significant problem. PMID:23903542

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

    PubMed

    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.

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

    PubMed Central

    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

    2006-01-01

    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 ≈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. PMID:16585527

  5. T Helper 1 (Th1), Th2, and Th17 Responses to Leishmania major Lipophosphoglycan 3.

    PubMed

    Miahipour, Abolfazl; Haji-Fatahaliha, Mostafa; Keshavarz, Hossein; Gharavi, Mohammad Javad; Mohamadi, Hamed; Babaloo, Zohre; Rafati, Sima; Younesi, Vahid; Hosseini, Maryam; Yousefi, Mehdi

    2016-10-01

    Leishmania major is the main causal agent of cutaneous leishmaniasis (CL) that remains a serious public health concern in many tropical and subtropical countries. A long-lasting protective vaccine against leishmaniasis remains as a medical unmet need. Lipophosphoglycan 3 (LPG3) is one of the class II LPG genes from HSP90 family involved in the host immune responses. The aim of the present study is to investigate the capability of recombinant LPG3 (rLPG3) to induce Th1, Th2, Th17 responses. The results showed that rLPG3 in moderate and high concentrations significantly induced expression of Th1 lineage-specific transcription factor (T-bet) and cytokine (IFN-γ)(P < 0.05). Moreover, the Th1-stimulating effect of rLPG3 was confirmed by significant induction of IFN-γ secretion from treated T cells (P < 0.01). However, no significant effect of rLPG3 on Th2 and Th17 lineage cells was observed even in high concentration. Our findings demonstrate that rLPG3 induces Th1, but not Th2 and Th17, lineage responses. Further studies are needed to investigate adjuvant properties of rLPG3 for leishmania therapy. PMID:27611455

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

    PubMed

    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 PMID:27031606

  7. Deficits in the 30-Hz auditory steady-state response in patients with major depressive disorder.

    PubMed

    Chen, Jingjing; Gong, Qin; Wu, Fei

    2016-10-19

    The auditory steady-state response (ASSR) is an auditory evoked potential that occurs in response to periodically presented auditory stimuli. The ASSR has drawn attention as a biomarker of psychiatric disorders owing to its connection with neural oscillations as well as its easy and noninvasive recording. Abnormalities in the γ band ASSR have been found consistently in patients with schizophrenia and bipolar disorder. However, although major depressive disorder (MDD) is also part of the common psychiatric diseases, the relationship between the ASSR and MDD has not been characterized sufficiently. Thus, the aim of the present study was to examine the ASSRs from patients with MDD and compare them with those from healthy control (HC) participants. The experiment was designed to obtain the ASSRs elicited by 20-, 30-, and 40-Hz click trains. Patients and HCs were evaluated separately. The response power and phase synchronization were measured at each stimulation frequency. Patients with MDD showed significantly reduced ASSR power for 30-Hz stimuli compared with HC participants, whereas no significant differences in the power were observed at 20 and 40 Hz for patients with MDD. In addition, no significant difference in the phase synchronization was observed for 20-, 30-, and 40-Hz stimuli. Conclusively, patients with MDD were characterized by deficits in 30-Hz ASSR power, which may be associated with spontaneous γ activity dysfunction. The present findings suggest that ASSR could potentially be used as a biomarker for MDD. PMID:27563737

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

    NASA Astrophysics Data System (ADS)

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

    NASA Astrophysics Data System (ADS)

    Fujiwara, M.; Hibino, T.; Mehta, S. K.; Gray, L.; Mitchell, D.; Anstey, J.

    2015-12-01

    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 geoengineering by stratospheric

  10. Tracking molecular evolution of photosynthesis by characterization of a major photosynthesis gene cluster from Heliobacillus mobilis

    PubMed Central

    Xiong, Jin; Inoue, Kazuhito; Bauer, Carl E.

    1998-01-01

    A DNA sequence has been obtained for a 35.6-kb genomic segment from Heliobacillus mobilis that contains a major cluster of photosynthesis genes. A total of 30 ORFs were identified, 20 of which encode enzymes for bacteriochlorophyll and carotenoid biosynthesis, reaction-center (RC) apoprotein, and cytochromes for cyclic electron transport. Donor side electron-transfer components to the RC include a putative RC-associated cytochrome c553 and a unique four-large-subunit cytochrome bc complex consisting of Rieske Fe-S protein (encoded by petC), cytochrome b6 (petB), subunit IV (petD), and a diheme cytochrome c (petX). Phylogenetic analysis of various photosynthesis gene products indicates a consistent grouping of oxygenic lineages that are distinct and descendent from anoxygenic lineages. In addition, H. mobilis was placed as the closest relative to cyanobacteria, which form a monophyletic origin to chloroplast-based photosynthetic lineages. The consensus of the photosynthesis gene trees also indicates that purple bacteria are the earliest emerging photosynthetic lineage. Our analysis also indicates that an ancient gene-duplication event giving rise to the paralogous bchI and bchD genes predates the divergence of all photosynthetic groups. In addition, our analysis of gene duplication of the photosystem I and photosystem II core polypeptides supports a “heterologous fusion model” for the origin and evolution of oxygenic photosynthesis. PMID:9843979

  11. Molecular Cloning and Expression of a New Major Allergen, Ani s 14, from Anisakis simplex.

    PubMed

    Kobayashi, Yukihiro; Kakemoto, Seiko; Shimakura, Kuniyoshi; Shiomi, Kazuo

    2015-01-01

    The nematode Anisakis simplex is a representative parasite infecting marine animals. When third stage larvae of A. simplex infecting fish and squids are ingested by humans, individuals previously sensitized by this parasite may experience IgE-mediated allergic reactions. So far, as many as 13 kinds of proteins (Ani s 1-13) have been identified as A. simplex allergens but several more unknown allergens are suggested to exist. In this study, therefore, chemiluminescent immunoscreening of an expression cDNA library constructed from the third stage larvae was conducted to identify a new allergen. As a result, an IgE-positive clone coding for a 23.5 kDa protein (named Ani s 14) composed of 217 amino acid residues was isolated. The regions 4-147 and 34-123 of Ani s 14 share 31% identity with the region 796-940 of Ani s 7 and 32% identity with the region 2-91 of Ani s 12, respectively. Recombinant Ani s 14 was successfully expressed in Escherichia coli as a His-tagged protein and shown to be IgE reactive to 14 (54%) of 26 sera from Anisakis-allergic patients. In conclusion, Ani s 14 is a new major allergen of A. simplex that is specific to Anisakis-allergic patients.

  12. Major Intercontinentally Distributed Sequence Types of Kingella kingae and Development of a Rapid Molecular Typing Tool

    PubMed Central

    Basmaci, Romain; Bidet, Philippe; Yagupsky, Pablo; Muñoz-Almagro, Carmen; Balashova, Nataliya V.; Doit, Catherine

    2014-01-01

    Although Kingella kingae is the most common etiology of osteoarticular infections in young children, is a frequent cause of bacteremia in those younger than 4 years, and has been involved in clusters of invasive infections among daycare center attendees, the population structure of the species has not been systematically studied. Using multilocus sequence typing, we investigated the genetic diversity of the largest intercontinental collection of K. kingae strains to date. To facilitate typing of bacterial isolates, we developed a novel genotyping tool that targets the DNA uptake sequence (DUS). Among 324 strains isolated from asymptomatic carriers and patients from Israel, Europe, North America, and Australia with various invasive forms of the disease from 1960 to 2013, we identified 64 sequence types (STs) and 12 ST complexes (STcs). Five predominant STcs, comprising 72.2% of all strains, were distributed intercontinentally. ST-6 was the most frequent, showing a worldwide distribution, and appeared genotypically isolated by exhibiting few neighboring STs, suggesting an optimal fitness. ST-14 and ST-23 appeared to be the oldest groups of bacteria, while ST-25 probably emerged more recently from the highly evolutive ST-23. Using the DUS typing method, randomly chosen isolates were correctly classified to one of the major STcs. The comprehensive description of K. kingae evolution would help to detect new emerging clones and decipher virulence and fitness mechanisms. The rapid and reproducible DUS typing method may serve in the initial investigation of K. kingae outbreaks. PMID:25143574

  13. Isolation and molecular characterization of a major hemolymph serpin from the triatomine, Panstrongylus megistus

    PubMed Central

    2014-01-01

    Background Chagas disease kills 2.5 thousand people per year of 15 million persons infected in Latin America. The disease is caused by the protozoan, Trypanosome cruzi, and vectored by triatomine insects, including Panstrongylus megistus, an important vector in Brazil. Medicines treating Chagas disease have unpleasant side effects and may be ineffective, therefore, alternative control techniques are required. Knowledge of the T. cruzi interactions with the triatomine host needs extending and new targets/strategies for control identified. Serine and cysteine peptidases play vital roles in protozoan life cycles including invasion and entry of T. cruzi into host cells. Peptidase inhibitors are, therefore, promising targets for disease control. Methods SDS PAGE and chromatograpy detected and isolated a P. megistus serpin which was peptide sequenced by mass spectrometry. A full amino acid sequence was obtained from the cDNA and compared with other insect serpins. Reverse transcription PCR analysis measured serpin transcripts of P. megistus tissues with and without T. cruzi infection. Serpin homology modeling used the Swiss Model and Swiss-PDB viewer programmes. Results The P. megistus serpin (PMSRP1) has a ca. 40 kDa molecular mass with 404 amino acid residues. A reactive site loop contains a highly conserved hinge region but, based on sequence alignment, the normal cleavage site for serine proteases at P1-P1′ was translocated to the putative position P4′-P5′. A small peptide obtained corresponded to the C-terminal 40 amino acid region. The secondary structure of PMSRP1 indicated nine α-helices and three β-sheets, similar to other serpins. PMSRP1 transcripts occurred in all tested tissues but were highest in the fat body and hemocytes. Levels of mRNA encoding PMSRP1 were significantly modulated in the hemocytes and stomach by T. cruzi infection indicating a role for PMSRP1 in the parasite interactions with P. megistus. Conclusions For the first time, a

  14. pH response and molecular recognition in a low molecular weight peptide hydrogel.

    PubMed

    Lange, Stefanie C; Unsleber, Jan; Drücker, Patrick; Galla, Hans-Joachim; Waller, Mark P; Ravoo, Bart Jan

    2015-01-14

    In this article we report the preparation and characterization of a peptide-based hydrogel, which possesses characteristic rheological properties, is pH responsive and can be functionalized at its thiol function. The tripeptide N-(fluorenyl-9-methoxycarbonyl)-L-Cys(acetamidomethyl)-L-His-L-Cys-OH 1 forms stable supramolecular aggregates in water leading to hydrogels above 1.5 wt%. Rheological analysis of the hydrogel revealed visco-elastic and shear thinning properties of samples containing 1.5 wt% of peptide 1. The hydrogel reversibly responds to pH changes. Below and above pH 6, electrostatic repulsion of the peptide results in a weakening of the three-dimensional gel network. Based on atomic force microscopy, small angle X-ray scattering and molecular dynamics simulations, it is proposed that the peptide assembles into nanostructures that tend to entangle at higher concentrations in water. The development of functional materials based on the peptide assemblies was possible via thiol-ene-click chemistry of the free thiol function at the C-terminal cysteine unit. As a proof of concept, the functionalization with adamantyl units to give 1-Ad was shown by molecular recognition of β-cyclodextrin vesicles. These vesicles were used as supramolecular cross-linkers of the assemblies of peptide 1 mixed with peptide 1-Ad leading to gel networks at a reduced peptide concentration.

  15. Molecular Cytogenetics in Digenean Parasites: Linked and Unlinked Major and 5S rDNAs, B Chromosomes and Karyotype Diversification.

    PubMed

    García-Souto, Daniel; Pasantes, Juan J

    2015-01-01

    Digenetic trematodes are the largest group of internal metazoan parasites, but their chromosomes are poorly studied. Although chromosome numbers and/or karyotypes are known for about 300 of the 18,000 described species, molecular cytogenetic knowledge is mostly limited to the mapping of telomeric sequences and/or of major rDNA clusters in 9 species. In this work we mapped major and 5S rDNA clusters and telomeric sequences in chromosomes of Bucephalus minimus, B. australis, Prosorhynchoides carvajali (Bucephaloidea), Monascus filiformis (Gymnophalloidea), Parorchis acanthus (Echinostomatoidea), Cryptocotyle lingua (Opisthorchioidea), Cercaria longicaudata, Monorchis parvus (Monorchioidea), Diphterostomum brusinae, and Bacciger bacciger (Microphalloidea). Whilst single major and minor rDNA clusters were mapped to different chromosome pairs in B. minimus and P. acanthus, overlapping signals were detected on a single chromosome pair in the remaining taxa. FISH experiments using major rDNA and telomeric probes clearly demonstrated the presence of highly stretched NORs in most of the digenean taxa analyzed. B chromosomes were detected in the B. bacciger samples hosted by Ruditapes decussatus. Although the cercariae specimens obtained from Donax trunculus, Tellina tenuis, and R. decussatus were in agreement with B. bacciger, their karyotypes showed striking morphological differences in agreement with the proposed assignation of these cercariae to different species of the genus Bacciger. Results are discussed in comparison with previous data on digenean chromosomes. PMID:26680763

  16. Computing Molecular Devices in L.major through Transcriptome Analysis: Structured Simulation Approach.

    PubMed

    Bejugam, Pruthvi Raj; Singh, Shailza

    2016-01-01

    In the modern era of post genomics and transcriptomics, non-coding RNAs and non-coding regions of many RNAs are a big puzzle when we try deciphering their role in specific gene function. Gene function assessment is a main task wherein high throughput technologies provide an impressive body of data that enables the design of hypotheses linking genes to phenotypes. Gene knockdown technologies and RNA-dependent gene silencing are the most frequent approaches to assess the role of key effectors in a particular scenario. Ribozymes are effective modulators of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. In our study, after an extensive transcriptomic search of Leishmania major transcriptome we found a Putative ATP dependent DNA helicase (Lmjf_09_0590) 3' UTR which has a structural signature similar to well-known HDV hammerhead ribozyme, even though they have variable sequence motifs. Henceforth, to determine their structural stability and sustainability we analyzed our predicted structural model of this 3'UTR with a 30ns MD simulation, further confirmed with 100ns MD simulation in presence of 5mM MgCl2 ionic environment. In this environment, structural stability was significantly improved by bonded interactions between a RNA backbone and Mg2+ ions. These predictions were further validated in silico using RNA normal mode analysis and anisotropic network modelling (ANM) studies. The study may be significantly imparted to know the functional importance of many such 3'UTRs to predict their role in a mechanistic manner. PMID:26901858

  17. Computing Molecular Devices in L.major through Transcriptome Analysis: Structured Simulation Approach

    PubMed Central

    Bejugam, Pruthvi Raj; Singh, Shailza

    2016-01-01

    In the modern era of post genomics and transcriptomics, non-coding RNAs and non-coding regions of many RNAs are a big puzzle when we try deciphering their role in specific gene function. Gene function assessment is a main task wherein high throughput technologies provide an impressive body of data that enables the design of hypotheses linking genes to phenotypes. Gene knockdown technologies and RNA-dependent gene silencing are the most frequent approaches to assess the role of key effectors in a particular scenario. Ribozymes are effective modulators of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. In our study, after an extensive transcriptomic search of Leishmania major transcriptome we found a Putative ATP dependent DNA helicase (Lmjf_09_0590) 3’ UTR which has a structural signature similar to well-known HDV hammerhead ribozyme, even though they have variable sequence motifs. Henceforth, to determine their structural stability and sustainability we analyzed our predicted structural model of this 3’UTR with a 30ns MD simulation, further confirmed with 100ns MD simulation in presence of 5mM MgCl2 ionic environment. In this environment, structural stability was significantly improved by bonded interactions between a RNA backbone and Mg2+ ions. These predictions were further validated in silico using RNA normal mode analysis and anisotropic network modelling (ANM) studies. The study may be significantly imparted to know the functional importance of many such 3’UTRs to predict their role in a mechanistic manner. PMID:26901858

  18. Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Subjects with Major Depressive Disorder

    PubMed Central

    Pizzagalli, Diego A.; Holmes, Avram J.; Dillon, Daniel G.; Goetz, Elena L.; Birk, Jeffrey L.; Bogdan, Ryan; Dougherty, Darin D.; Iosifescu, Dan V.; Rauch, Scott L.; Fava, Maurizio

    2009-01-01

    Objective Major depressive disorder (MDD) is characterized by impaired reward processing, possibly due to dysfunction in the basal ganglia. However, few neuroimaging studies of depression have distinguished between anticipatory and consummatory phases of reward processing. Using functional magnetic resonance imaging (fMRI) and a task that dissociates anticipatory and consummatory phases of reward processing, the authors tested the hypothesis that MDD participants would show reduced reward-related responses in basal ganglia structures. Method A monetary incentive delay task was presented to 30 unmedicated MDD subjects and 31 healthy comparison subjects during fMRI scanning. Whole-brain analyses focused on neural responses to reward-predicting cues and rewarding outcomes (i.e., monetary gains). Secondary analyses focused on the relationship between anhedonic symptoms and basal ganglia volumes. Results Relative to comparison subjects, MDD participants showed significantly weaker responses to gains in the left nucleus accumbens and bilateral caudate. Group differences in these regions were specific to rewarding outcomes and did not generalize to neutral or negative outcomes, although relatively reduced responses to monetary penalties in MDD emerged in other caudate regions. By contrast, evidence for group differences during reward anticipation was weaker, although MDD subjects showed reduced activation to reward cues in a small sector of the left posterior putamen. Among MDD subjects, anhedonic symptoms and depression severity were associated with reduced bilateral caudate volume. Conclusions These results indicate that basal ganglia dysfunction in MDD may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in MDD is related to caudate volume. PMID:19411368

  19. Effects of Duloxetine Treatment on Brain Response to Painful Stimulation in Major Depressive Disorder

    PubMed Central

    López-Solà, Marina; Pujol, Jesus; Hernández-Ribas, Rosa; Harrison, Ben J; Contreras-Rodríguez, Oren; Soriano-Mas, Carles; Deus, Joan; Ortiz, Héctor; Menchón, José M; Vallejo, Julio; Cardoner, Narcís

    2010-01-01

    Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology. PMID:20668437

  20. Responses of plant seedlings to hypergravity: cellular and molecular aspects

    NASA Astrophysics Data System (ADS)

    Hoson, T.; Yoshioka, R.; Soga, K.; Wakabayashi, K.; Takeba, G.

    Hypergravity produced by centrifugation has been used to analyze the responses of plant seedlings to gravity stimulus. Elongation growth of stem organs is suppressed by hypergravity, which can be recognized as a way for plants to resist gravitational force. The mechanisms inducing growth suppression under hypergravity conditions were analyzed at cellular and molecular levels. When growth was suppressed by hypergravity, a decrease in the cell wall extensibility was brought about in various plants. Hypergravity also induced a cell wall thickening and an increase in the molecular mass of the certain hemicellulosic polysaccharides. Both a decrease in the activities hydrolyzing such polysaccharides and an increase in the apoplast pH were involved in such changes in the cell wall constituents. Thus, the cell wall metabolism is greatly modified under hypergravity conditions, which causes a decrease in the cell wall extensibility, thereby inhibiting elongation growth in stem organs. On the other hand, to identify genes involved in hypergravity-induced growth suppression, changes in gene expression by hypergravity treatment were analyzed in Arabidopsis hypocotyls by differential display method. Sixty-two genes were expressed differentially: expression levels of 39 genes increased, whereas those of 23 genes decreased under hypergravity conditions. The expression of these genes was further analyzed using RT-PCR. One of genes upregulated by hypergravity encoded hydroxymethylglutaryl-CoA reductase (HMGR), which catalyzes a reaction producing mevalonic acid, a key precursor of hormones such as gibberellic acid and abscisic acid. The expression of HMGR gene increased within several hours after hypergravity treatment. Also, compactin, an inhibitor of HMGR activity, prevented hypergravity-induced growth suppression, suggesting that HMGR is involved in suppression of Arabidopsis hypocotyl growth by hypergravity. In addition, hypergravity increased the expression levels of CCR1 and

  1. The domestication syndrome genes responsible for the major changes in plant form in the Triticeae crops.

    PubMed

    Sakuma, Shun; Salomon, Björn; Komatsuda, Takao

    2011-05-01

    The process of crop domestication began 10,000 years ago in the transition of early humans from hunter/gatherers to pastoralists/farmers. Recent research has revealed the identity of some of the main genes responsible for domestication. Two of the major domestication events in barley were (i) the failure of the spike to disarticulate and (ii) the six-rowed spike. The former mutation increased grain yield by preventing grain loss after maturity, while the latter resulted in an up to 3-fold increase in yield potential. Here we provide an overview of the disarticulation systems and inflorescence characteristics, along with the genes underlying these traits, occurring in the Triticeae tribe.

  2. The Domestication Syndrome Genes Responsible for the Major Changes in Plant Form in the Triticeae Crops

    PubMed Central

    Sakuma, Shun; Salomon, Björn; Komatsuda, Takao

    2011-01-01

    The process of crop domestication began 10,000 years ago in the transition of early humans from hunter/gatherers to pastoralists/farmers. Recent research has revealed the identity of some of the main genes responsible for domestication. Two of the major domestication events in barley were (i) the failure of the spike to disarticulate and (ii) the six-rowed spike. The former mutation increased grain yield by preventing grain loss after maturity, while the latter resulted in an up to 3-fold increase in yield potential. Here we provide an overview of the disarticulation systems and inflorescence characteristics, along with the genes underlying these traits, occurring in the Triticeae tribe. PMID:21389058

  3. Resting-state connectivity predictors of response to psychotherapy in major depressive disorder.

    PubMed

    Crowther, Andrew; Smoski, Moria J; Minkel, Jared; Moore, Tyler; Gibbs, Devin; Petty, Chris; Bizzell, Josh; Schiller, Crystal Edler; Sideris, John; Carl, Hannah; Dichter, Gabriel S

    2015-06-01

    Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment

  4. Quantitative Molecular Detection of 19 Major Pathogens in the Interdental Biofilm of Periodontally Healthy Young Adults

    PubMed Central

    Carrouel, Florence; Viennot, Stéphane; Santamaria, Julie; Veber, Philippe; Bourgeois, Denis

    2016-01-01

    In oral health, the interdental spaces are a real ecological niche for which the body has few or no alternative defenses and where the traditional daily methods for control by disrupting biofilm are not adequate. The interdental spaces are the source of many hypotheses regarding their potential associations with and/or causes of cardiovascular disease, diabetes, chronic kidney disease, degenerative disease, and depression. This PCR study is the first to describe the interdental microbiota in healthy adults aged 18–35 years-old with reference to the Socransky complexes. The complexes tended to reflect microbial succession events in developing dental biofilms. Early colonizers included members of the yellow, green, and purple complexes. The orange complex bacteria generally appear after the early colonizers and include many putative periodontal pathogens, such as Fusobacterium nucleatum. The red complex (Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) was considered the climax community and is on the list of putative periodontal pathogens. The 19 major periodontal pathogens tested were expressed at various levels. F. nucleatum was the most abundant species, and the least abundant were Actinomyces viscosus, P. gingivalis, and Aggregatibacter actinomycetemcomitans. The genome counts for Eikenella corrodens, Campylobacter concisus, Campylobacter rectus, T. denticola, and Tannerella forsythensis increased significantly with subject age. The study highlights the observation that bacteria from the yellow complex (Streptococcus spp., S. mitis), the green complex (E. corrodens, Campylobacter gracilis, Capnocytophaga ochracea, Capnocytophaga sputigena, A. actinomycetemcomitans), the purple complex (Veillonella parvula, Actinomyces odontolyticus) and the blue complex (A. viscosus) are correlated. Concerning the orange complex, F. nucleatum is the most abundant species in interdental biofilm. The red complex, which is recognized as the most important

  5. Quantitative Molecular Detection of 19 Major Pathogens in the Interdental Biofilm of Periodontally Healthy Young Adults.

    PubMed

    Carrouel, Florence; Viennot, Stéphane; Santamaria, Julie; Veber, Philippe; Bourgeois, Denis

    2016-01-01

    In oral health, the interdental spaces are a real ecological niche for which the body has few or no alternative defenses and where the traditional daily methods for control by disrupting biofilm are not adequate. The interdental spaces are the source of many hypotheses regarding their potential associations with and/or causes of cardiovascular disease, diabetes, chronic kidney disease, degenerative disease, and depression. This PCR study is the first to describe the interdental microbiota in healthy adults aged 18-35 years-old with reference to the Socransky complexes. The complexes tended to reflect microbial succession events in developing dental biofilms. Early colonizers included members of the yellow, green, and purple complexes. The orange complex bacteria generally appear after the early colonizers and include many putative periodontal pathogens, such as Fusobacterium nucleatum. The red complex (Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) was considered the climax community and is on the list of putative periodontal pathogens. The 19 major periodontal pathogens tested were expressed at various levels. F. nucleatum was the most abundant species, and the least abundant were Actinomyces viscosus, P. gingivalis, and Aggregatibacter actinomycetemcomitans. The genome counts for Eikenella corrodens, Campylobacter concisus, Campylobacter rectus, T. denticola, and Tannerella forsythensis increased significantly with subject age. The study highlights the observation that bacteria from the yellow complex (Streptococcus spp., S. mitis), the green complex (E. corrodens, Campylobacter gracilis, Capnocytophaga ochracea, Capnocytophaga sputigena, A. actinomycetemcomitans), the purple complex (Veillonella parvula, Actinomyces odontolyticus) and the blue complex (A. viscosus) are correlated. Concerning the orange complex, F. nucleatum is the most abundant species in interdental biofilm. The red complex, which is recognized as the most important

  6. Does Speciation between Arabidopsis halleri and Arabidopsis lyrata Coincide with Major Changes in a Molecular Target of Adaptation?

    PubMed Central

    Roux, Camille; Castric, Vincent; Pauwels, Maxime; Wright, Stephen I.; Saumitou-Laprade, Pierre; Vekemans, Xavier

    2011-01-01

    Ever since Darwin proposed natural selection as the driving force for the origin of species, the role of adaptive processes in speciation has remained controversial. In particular, a largely unsolved issue is whether key divergent ecological adaptations are associated with speciation events or evolve secondarily within sister species after the split. The plant Arabidopsis halleri is one of the few species able to colonize soils highly enriched in zinc and cadmium. Recent advances in the molecular genetics of adaptation show that the physiology of this derived ecological trait involves copy number expansions of the AhHMA4 gene, for which orthologs are found in single copy in the closely related A. lyrata and the outgroup A. thaliana. To gain insight into the speciation process, we ask whether adaptive molecular changes at this candidate gene were contemporary with important stages of the speciation process. We first inferred the scenario and timescale of speciation by comparing patterns of variation across the genomic backgrounds of A. halleri and A. lyrata. Then, we estimated the timing of the first duplication of AhHMA4 in A. halleri. Our analysis suggests that the historical split between the two species closely coincides with major changes in this molecular target of adaptation in the A. halleri lineage. These results clearly indicate that these changes evolved in A. halleri well before industrial activities fostered the spread of Zn- and Cd-polluted areas, and suggest that adaptive processes related to heavy-metal homeostasis played a major role in the speciation process. PMID:22069475

  7. The time-dependent dynamical response of the thermosphere to major geomagnetic disturbances

    NASA Technical Reports Server (NTRS)

    Rees, D.

    1986-01-01

    Several recent observations of thermospheric dynamics, made in the polar regions during extremely disturbed geomagnetic periods are reviewed. In general, the magnitude and the variability of winds in the thermospheric polar regions increases with magnetic activity, as measured by any of the conventional indices. However, none of the conventional indices is a particularly good aid to predicting wind magnitudes. In very general terms, two major factors may be considered in describing the wind system. The magnitude of the Interplanetary Magnetic Field (IMF) and, in particular, its southward component, determine the size of the auroral oval, and the strength of the cross-polar cap potential. This determines the size of the auroral oval, the magnitude of the sunward winds in the auroral oval and of those blowing anti-sunward over the polar cap, and is probably the major factor in determining the rate of geomagnetic energy deposition in the thermosphere. Superimposed on this enhanced polar circulation system are the effects of discrete auroral substorms. From a global view point, the effect of substorms is to generate a series of strong disturbances which propagate from their source region, usually near magnetic midnight in the auroral oval. The energy associated with discrete substorms is, however, usually a rather small proportion of the total global geomagnetic input during disturbed periods. These observations of thermospheric wind disturbances will be evaluated by comparison with global simulations of the thermospheric response to theoretical and semi-empirical models of the polar electric field, and of the effects of magnetospheric particle precipitation.

  8. Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E.

    PubMed

    Hansen, Scott G; Wu, Helen L; Burwitz, Benjamin J; Hughes, Colette M; Hammond, Katherine B; Ventura, Abigail B; Reed, Jason S; Gilbride, Roxanne M; Ainslie, Emily; Morrow, David W; Ford, Julia C; Selseth, Andrea N; Pathak, Reesab; Malouli, Daniel; Legasse, Alfred W; Axthelm, Michael K; Nelson, Jay A; Gillespie, Geraldine M; Walters, Lucy C; Brackenridge, Simon; Sharpe, Hannah R; López, César A; Früh, Klaus; Korber, Bette T; McMichael, Andrew J; Gnanakaran, S; Sacha, Jonah B; Picker, Louis J

    2016-02-12

    Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ(+) T cells, at ~4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8(+) T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy. PMID:26797147

  9. Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E

    DOE PAGESBeta

    Hansen, Scott G.; Wu, Helen L.; Burwits, Benjamin J.; Hughes, Colette M.; Hammond, Katherine B.; Ventura, Abigail B.; Reed, Jason S.; Gilbride, Roxanne M.; Ainslie, Emily; Morrow, David W.; et al

    2016-02-12

    Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, nonclassical, MHC-Ib molecule with limited polymorphism primarily involved in regulation of NK cell reactivity via interaction with NKG2/CD94 receptors. We found that vaccination of rhesus macaques with Rh157.5/.4 gene-deleted rhesus Cytomegalovirus (RhCMV) vectors uniquely diverts MHC-E function to presentation of highly diverse peptide epitopes to CD8α/β+ T cells, approximately 4 distinct epitopes per 100 amino acids, in all tested protein antigens. Computational structural analysis revealed that a relatively stable, open binding groove in MHC-E attains broad peptide binding specificity by imposing a similar backbone configuration on bound peptides with fewmore » restrictions based on amino acid side chains. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.« less

  10. Property-optimized Gaussian basis sets for molecular response calculations

    NASA Astrophysics Data System (ADS)

    Rappoport, Dmitrij; Furche, Filipp

    2010-10-01

    With recent advances in electronic structure methods, first-principles calculations of electronic response properties, such as linear and nonlinear polarizabilities, have become possible for molecules with more than 100 atoms. Basis set incompleteness is typically the main source of error in such calculations since traditional diffuse augmented basis sets are too costly to use or suffer from near linear dependence. To address this problem, we construct the first comprehensive set of property-optimized augmented basis sets for elements H-Rn except lanthanides. The new basis sets build on the Karlsruhe segmented contracted basis sets of split-valence to quadruple-zeta valence quality and add a small number of moderately diffuse basis functions. The exponents are determined variationally by maximization of atomic Hartree-Fock polarizabilities using analytical derivative methods. The performance of the resulting basis sets is assessed using a set of 313 molecular static Hartree-Fock polarizabilities. The mean absolute basis set errors are 3.6%, 1.1%, and 0.3% for property-optimized basis sets of split-valence, triple-zeta, and quadruple-zeta valence quality, respectively. Density functional and second-order Møller-Plesset polarizabilities show similar basis set convergence. We demonstrate the efficiency of our basis sets by computing static polarizabilities of icosahedral fullerenes up to C720 using hybrid density functional theory.

  11. A pH-responsive molecular switch with tricolor luminescence.

    PubMed

    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. PMID:25532587

  12. Mercury toxicity, molecular response and tolerance in higher plants.

    PubMed

    Chen, Jian; Yang, Zhi Min

    2012-10-01

    Mercury (Hg) contamination in soils has become a great concern as a result of its natural release and anthropogenic activities. This review presents broad aspects of our recent understanding of mercury contamination and toxicology in plants including source of Hg contamination, toxicology, tolerant regulation in plants, and minimization strategy. We first introduced the sources of mercury contamination in soils. Mercury exists in different forms, but ionic mercury (Hg(2+)) is the predominant form in soils and readily absorbed by plants. The second issue to be discussed is the uptake, transport, and localization of Hg(2+) in plants. Mercury accumulated in plants evokes severe phytotoxicity and impairs numerous metabolic processes including nutrient uptake, water status, and photosynthesis. The mechanisms of mercury-induced toxicology, molecular response and gene networks for regulating plant tolerance will be reviewed. In the case of Hg recent much progress has been made in profiling of transcriptome and more importantly, uncovering a group of small RNAs that potentially mediates plant tolerance to Hg. Several newly discovered signaling molecules such as nitric oxide and carbon monoxide have now been described as regulators of plant tolerance to Hg. A recently emerged strategy, namely selection and breeding of plant cultivars to minimize Hg (or other metals) accumulation will be discussed in the last part of the review.

  13. Response conflict and frontocingulate dysfunction in unmedicated participants with Major Depression

    PubMed Central

    Holmes, Avram J.; Pizzagalli, Diego A.

    2008-01-01

    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. PMID:18577391

  14. Numerical and Functional Responses of Forest Bats to a Major Insect Pest in Pine Plantations

    PubMed Central

    Charbonnier, Yohan; Barbaro, Luc; Theillout, Amandine; Jactel, Hervé

    2014-01-01

    Global change is expected to modify the frequency and magnitude of defoliating insect outbreaks in forest ecosystems. Bats are increasingly acknowledged as effective biocontrol agents for pest insect populations. However, a better understanding is required of whether and how bat communities contribute to the resilience of forests to man- and climate-driven biotic disturbances. We studied the responses of forest insectivorous bats to a major pine defoliator, the pine processionary moth pityocampa, which is currently expanding its range in response to global warming. We used pheromone traps and ultrasound bat recorders to estimate the abundance and activity of moths and predatory bats along the edge of infested pine stands. We used synthetic pheromone to evaluate the effects of experimentally increased moth availability on bat foraging activity. We also evaluated the top-down regulation of moth population by estimating T. pityocampa larval colonies abundance on the same edges the following winter. We observed a close spatio-temporal matching between emergent moths and foraging bats, with bat activity significantly increasing with moth abundance. The foraging activity of some bat species was significantly higher near pheromone lures, i.e. in areas of expected increased prey availability. Furthermore moth reproductive success significantly decreased with increasing bat activity during the flight period of adult moths. These findings suggest that bats, at least in condition of low prey density, exhibit numerical and functional responses to a specific and abundant prey, which may ultimately result in an effective top-down regulation of the population of the prey. These observations are consistent with bats being useful agents for the biocontrol of insect pest populations in plantation forests. PMID:25285523

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

    PubMed Central

    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

  16. Activation of Molecular Signatures for Antimicrobial and Innate Defense Responses in Skin with Transglutaminase 1 Deficiency.

    PubMed

    Haneda, Takashi; Imai, Yasutomo; Uchiyama, Ryosuke; Jitsukawa, Orie; Yamanishi, Kiyofumi

    2016-01-01

    Mutations of the transglutaminase 1 gene (TGM1) are a major cause of autosomal recessive congenital ichthyoses (ARCIs) that are associated with defects in skin barrier structure and function. However, the molecular processes induced by the transglutaminase 1 deficiency are not fully understood. The aim of the present study was to uncover those processes by analysis of cutaneous molecular signatures. Gene expression profiles of wild-type and Tgm1-/-epidermis were assessed using microarrays. Gene ontology analysis of the data showed that genes for innate defense responses were up-regulated in Tgm1-/-epidermis. Based on that result, the induction of Il1b and antimicrobial peptide genes, S100a8, S100a9, Defb14, Camp, Slpi, Lcn2, Ccl20 and Wfdc12, was confirmed by quantitative real-time PCR. A protein array revealed that levels of IL-1β, G-CSF, GM-CSF, CXCL1, CXCL2, CXCL9 and CCL2 were increased in Tgm1-/-skin. Epidermal growth factor receptor (EGFR) ligand genes, Hbegf, Areg and Ereg, were activated in Tgm1-/-epidermis. Furthermore, the antimicrobial activity of an epidermal extract from Tgm1-/-mice was significantly increased against both Escherichia coli and Staphylococcus aureus. In the epidermis of ichthyosiform skins from patients with TGM1 mutations, S100A8/9 was strongly positive. The expression of those antimicrobial and defense response genes was also increased in the lesional skin of an ARCI patient with TGM1 mutations. These results suggest that the up-regulation of molecular signatures for antimicrobial and innate defense responses is characteristic of skin with a transglutaminase 1 deficiency, and this autonomous process might be induced to reinforce the defective barrier function of the skin. PMID:27442430

  17. Activation of Molecular Signatures for Antimicrobial and Innate Defense Responses in Skin with Transglutaminase 1 Deficiency

    PubMed Central

    Uchiyama, Ryosuke; Jitsukawa, Orie; Yamanishi, Kiyofumi

    2016-01-01

    Mutations of the transglutaminase 1 gene (TGM1) are a major cause of autosomal recessive congenital ichthyoses (ARCIs) that are associated with defects in skin barrier structure and function. However, the molecular processes induced by the transglutaminase 1 deficiency are not fully understood. The aim of the present study was to uncover those processes by analysis of cutaneous molecular signatures. Gene expression profiles of wild-type and Tgm1–/–epidermis were assessed using microarrays. Gene ontology analysis of the data showed that genes for innate defense responses were up-regulated in Tgm1–/–epidermis. Based on that result, the induction of Il1b and antimicrobial peptide genes, S100a8, S100a9, Defb14, Camp, Slpi, Lcn2, Ccl20 and Wfdc12, was confirmed by quantitative real-time PCR. A protein array revealed that levels of IL-1β, G-CSF, GM-CSF, CXCL1, CXCL2, CXCL9 and CCL2 were increased in Tgm1–/–skin. Epidermal growth factor receptor (EGFR) ligand genes, Hbegf, Areg and Ereg, were activated in Tgm1–/–epidermis. Furthermore, the antimicrobial activity of an epidermal extract from Tgm1–/–mice was significantly increased against both Escherichia coli and Staphylococcus aureus. In the epidermis of ichthyosiform skins from patients with TGM1 mutations, S100A8/9 was strongly positive. The expression of those antimicrobial and defense response genes was also increased in the lesional skin of an ARCI patient with TGM1 mutations. These results suggest that the up-regulation of molecular signatures for antimicrobial and innate defense responses is characteristic of skin with a transglutaminase 1 deficiency, and this autonomous process might be induced to reinforce the defective barrier function of the skin. PMID:27442430

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

    PubMed

    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. PMID:25264343

  19. Health risk assessment of major accidents with toxic chemicals for disaster preparedness and response

    SciTech Connect

    Van der Torn, P.

    1991-01-01

    Health risks of major accidents with toxic chemicals need to be defined by: (i) nature, (ii) number and (iii) severity. (ad i) Health effects are conveniently categorized by nature into local (L)/systemic (S) and immediate (1)/delayed (2) (health effects). (ad ii) Derivation of population responses generally is unfeasible, instead exposure bands can be specified by effect-level. (ad iii) The continuum of health effects should be described in a global disability scale. The 4 D'-scale seems most appropriate: death (D{sub 1}), disability (D{sub 2}), discomfort (D{sub 3}), detectability (D{sub 4}). For use in disaster response health risk specifications should furthermore be: (1) transparent, (2) in line with the overall situational analysis and (3) congruent with mitigation. (-ad 1) Transparency can be improved by selecting one main sign/symptom by effect level for field instructions. (-ad 2) Situational analysis initially involves the source-area (what effect levels are found near the source ) and the outer limits of the effect area (feedback from telephone complaints mostly D{sub 4}). Otherwise, knowledge is needed of the ratio of exposures that lead to consecutive effect levels to assess the overall health impact by interpolation. Finally, the need to recognize high risk situations is emphasized: e.g. data bases with distributions of dispersion constraints (urban areas), penetration potentials into the housing-stock, concentrations of groups at high-risk (over time). (-ad 3) Mitigation is divided into: (a) protection of the public in a threatened area and (b) medical assistance.

  20. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

    PubMed Central

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-01-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935). PMID:23716542

  1. A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

    PubMed

    Shinohara, Yoshinori; Takahashi, Naoto; Nishiwaki, Kaichi; Hino, Masayuki; Kashimura, Makoto; Wakita, Hisashi; Hatano, Yoshiaki; Hirasawa, Akira; Nakagawa, Yasuaki; Itoh, Kuniaki; Masuoka, Hidekazu; Aotsuka, Nobuyuki; Matsuura, Yasuhiro; Takahara, Sinobu; Sano, Koji; Kuroki, Jun; Hata, Tomoko; Nakamae, Hirohisa; Mugitani, Atsuko; Nakane, Takahiko; Miyazaki, Yasushi; Niioka, Takenori; Miura, Masatomo; Sawada, Kenichi

    2013-09-01

    Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

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

    ERIC Educational Resources Information Center

    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…

  3. Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance

    PubMed Central

    Ozekes, Serhat; Gultekin, Selahattin; Tarhan, Nevzat; Hizli Sayar, Gokben; Bayram, Ali

    2015-01-01

    Objective The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN). Methods The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation. Results The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively. Conclusion Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values. PMID:25670947

  4. Identification of Major Active Ingredients Responsible for Burn Wound Healing of Centella asiatica Herbs.

    PubMed

    Wu, Fang; Bian, Difei; Xia, Yufeng; Gong, Zhunan; Tan, Qian; Chen, Jiaojiao; Dai, Yue

    2012-01-01

    Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β(1) levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057 for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).

  5. Carrington 2? Estimated response of the magnetosphere to a major outburst'

    NASA Astrophysics Data System (ADS)

    Bala, R.; Reiff, P. H.; Russell, C. T.

    2013-12-01

    On July 23, 2012, a major CME outburst on the far side of the Sun was observed by STEREO A [Russell et al, 2013]. Because of its intensity and by the fact that it included a significant flux of SEP's, it has been hailed as "Carrington 2" by some, warning that, had that CME been heading towards the Earth, it might have caused a major space weather event. We then used our neural network algorithm to use the solar wind and IMF parameters measured in situ by STEREO A to infer what the geoeffectiveness of that storm might have been. We presently show three of our neural network models on our realtime prediction site: http://mms.rice.edu/realtime/forecast.html. The three models use different base functions, trained by a solar cycle worth of solar wind input and geomagnetic response data. One model uses the "Boyle Index" (BI) as the base transfer function (which includes Bz and velocity but not density). The "Ram" function includes the Boyle Index plus a pressure term. The "Newell" function uses the Newell formula which does include density. Statistically, each of them is good for either a one-hour or three-hour prediction to better than one unit in Kp. (Another talk will show the relative success of each as a realtime predictor). STEREO density data were not available for this event, so we chose as a density proxy the density from a similar event in April 2001. Running this "C2" event through our neural network predictors showed that, in fact, this would have been an exceptional (but perhaps not devastating) event. The BI prediction resulted in a Kp of 8+, a Dst of less than -300 nT, but an AE index of only 1000 nT. Using the "Ram" code, the Kp prediction increased to almost 9+, with Dst again below -300 nT and AE of 1200 nT. Results of a range of possible assumptions about the density structure will be shown.

  6. Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

    PubMed Central

    Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

    2015-01-01

    In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

  7. Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses.

    PubMed

    Pereira, Wânia F; Ribeiro-Gomes, Flávia L; Guillermo, Landi V Costilla; Vellozo, Natália S; Montalvão, Fabrício; Dosreis, George A; Lopes, Marcela F

    2011-12-01

    Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation.

  8. Catechins are not major components responsible for anti-genotoxic effects of tea extracts against nitroarenes.

    PubMed

    Ohe, T; Marutani, K; Nakase, S

    2001-09-20

    The anti-genotoxic properties of tea leaf extracts were examined in a Salmonella umu-test. Seven non-fermented teas (green tea), one semi-fermented tea (oolong tea), two fermented teas (black tea and Chinese pu er tea) and two other teas were examined for their anti-genotoxic abilities and for their catechins contents. This was to study the relationship between catechins contents and anti-genotoxic activity of various tea leaf extracts. All types of tea extracts showed more potent suppressive effects against umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK 1002 induced by four nitroarenes (1-nitropyrene, 2-nitrofluorene, 3-nitrofluoranthene and a mixture of 1,6- and 1,8-dinitropyrene) rather than 4-NQO, AF-2 and MNNG. The anti-genotoxic effect of 12 tea leaf extracts on 1-NP, 2-NF, 3-NF and DNP decreased in the order: oolong tea (semi-fermented tea)>black tea (fermented tea)>sencha (non-fermented tea, an ordinary grade green tea)>tocyucya (other tea)>Chinese pu er tea (fermented tea). The amount of catechins (EGC, C, EGCG, EC and ECG) in various teas in decreasing order was non-fermented tea>semi-fermented tea>fermented tea>other tea. A remarkable feature was the effectiveness of black tea and Chinese pu er tea in suppressing the genotoxicity induced by nitroarenes, in spite of the fact that these fermented teas do not have high catechins contents. Statistical analysis showed that no significant (P<0.01) correlation was found between the anti-genotoxicity of tea extracts against nitroarenes and the catechins contents in tea leaf extracts. In further experiment, fractionation of sencha extract by HPLC revealed that anti-genotoxicity of the peak fraction corresponding to catechins accounted for <10% of the total anti-genotoxic activity of sencha extract against for 1-nitropyrene. These results suggest that catechins are not major components responsible for the anti-genotoxic effects of tea leaf extracts against direct-acting nitroarenes

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

    PubMed

    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.

  10. Molecular Detection of Leishmania major and L. turanica in Phlebotomus papatasi and First Natural Infection of P. salehi to L. major in North-East of Iran

    PubMed Central

    Rafizadeh, Sayena; Saraei, Mehrzad; Abaei, Mohammad Reza; Oshaghi, Mohammad Ali; Mohebali, Mehdi; Peymani, Amir; Naserpour-Farivar, Taghi; Bakhshi, Hassan; Rassi, Yavar

    2016-01-01

    Background: Leishmaniasis is an important public health disease in many developing countries as well in Iran. The main objective of this study was to investigate on leishmania infection of wild caught sand flies in an endemic focus of disease in Esfarayen district, north east of Iran. Methods: Sand flies were collected by sticky papers and mounted in a drop of Puri’s medium for species identification. Polymerase chain reaction techniques of kDNA, ITS1-rDNA, followed by restriction fragment length polymorphism were used for identification of DNA of Leishmania parasites within infected sand flies. Results: Among the collected female sand flies, two species of Phlebotomus papatasi and Phlebotomus salehi were found naturally infected with Leishmania major. Furthermore, mixed infection of Leishmania turanica and L. major was observed in one specimen of P. papatasi. Sequence analysis revealed two parasite ITS1 haplotypes including three L. major with accession numbers: KJ425408, KJ425407, KM056403 and one L. turanica. (KJ425406). The haplotype of L. major was identical (100%) to several L. major sequences deposited in GenBank, including isolates from Iran, (Gen Bank accession nos.AY573187, KC505421, KJ194178) and Uzbekistan (Accession no.FN677357). Conclusion: To our knowledge, this is the first detection of L. major within wild caught P. salehi in northeast of Iran. PMID:27308272

  11. Serum antibody response to recombinant major inner capsid protein following human infection with group B rotavirus.

    PubMed Central

    Eiden, J J; Mouzinho, A; Lindsay, D A; Glass, R I; Fang, Z Y; Taylor, J L

    1994-01-01

    Recombinant major inner capsid protein (VP6) of the IDIR strain of group B rotavirus (GBR) was incorporated in a solid-phase immunoassay to access antibody response to infection in humans. Expression of VP6 in insect cells permitted design of a highly sensitive assay that avoided the contaminants present in GBR antigens obtained from fecal specimens. Among patients infected with the ADRV strain of GBR in China, increased reactivity with recombinant VP6 was observed in convalescent-phase sera in comparison with sera obtained shortly after infection (P = 0.0084). Anti-VP6 antibodies were detectable as soon as 7 days after onset of gastrointestinal symptoms, and serum reactivity persisted in specimens drawn more than 1 year after infection. Solid-phase immunoassay with recombinant VP6 was next employed in order to assess anti-GBR antibody in 513 serum specimens obtained from 423 Maryland residents (ages, 7 months to 96 years; median age, 42 years). Four individuals (< 1%) exhibited serum antibodies directed against the recombinant VP6 (ages, 54 to 95 years; mean age, 77 years). Examination of 129 additional serum specimens including some from other geographic regions of the United States failed to reveal the presence of anti-GBR antibody. Anti-GBR antibody was also not detected in any of 131 serum specimens from 60 staff and residents of a nursing home in Switzerland. While infection of humans with GBR has been uncommon in these locations outside of China, the detection of serum antibodies in older individuals in the United States either indicated an unknown, age-related risk factor or may have indicated infection in the more distant past. The availability of these reagents should allow surveys for GBR infection among additional populations that have not previously been investigated. PMID:8077413

  12. On the composite response of the MLT to major sudden stratospheric warming events with elevated stratopause

    NASA Astrophysics Data System (ADS)

    Limpasuvan, Varavut; Orsolini, Yvan J.; Chandran, Amal; Garcia, Rolando R.; Smith, Anne K.

    2016-05-01

    Based on a climate-chemistry model (constrained by reanalyses below ~50 km), the zonal-mean composite response of the mesosphere and lower thermosphere (MLT) to major sudden stratospheric warming events with elevated stratopauses demonstrates the role of planetary waves (PWs) in driving the mean circulation in the presence of gravity waves (GWs), helping the polar vortex recover and communicating the sudden stratospheric warming (SSW) impact across the equator. With the SSW onset, strong westward PW drag appears above 80 km primarily from the dissipation of wave number 1 perturbations with westward period of 5-12 days, generated from below by the unstable westward polar stratospheric jet that develops as a result of the SSW. The filtering effect of this jet also allows eastward propagating GWs to saturate in the winter MLT, providing eastward drag that promotes winter polar mesospheric cooling. The dominant PW forcing translates to a net westward drag above the eastward mesospheric jet, which initiates downwelling over the winter pole. As the eastward polar stratospheric jet returns, this westward PW drag persists above 80 km and acts synergistically with the return of westward GW drag to drive a stronger polar downwelling that warms the pole adiabatically and helps reform the stratopause at an elevated altitude. With the polar wind reversal during the SSW onset, the westward drag by the quasi-stationary PW in the winter stratosphere drives an anomalous equatorial upwelling and cooling that enhance tropical stratospheric ozone. Along with equatorial wind anomalies, this ozone enhancement subsequently amplifies the migrating semidiurnal tide amplitude in the winter midlatitudes.

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

    PubMed

    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 (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA 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.

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

    PubMed

    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

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

    PubMed

    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

  16. USGS Emergency Response and the International Charter Space and Major Disasters

    NASA Astrophysics Data System (ADS)

    Jones, B. K.

    2009-12-01

    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. FEMA’s partnership with the USGS began in 1999 when the agency established USGS as its executive agent for the acquisition and coordination of aerial and satellite remote sensing data. Understanding the terrain affords FEMA the vital perspective needed to effectively respond to the devastation many disasters leave behind. 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 space agencies, to information on their methodology in disaster response, and to data from the satellites they operate. 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 over 75 images to the US in support of Hurricane

  17. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism

    PubMed Central

    Chua, Han Chow; Christensen, Emilie T. H.; Hoestgaard-Jensen, Kirsten; Hartiadi, Leonny Y.; Ramzan, Iqbal; Jensen, Anders A.; Absalom, Nathan L.; Chebib, Mary

    2016-01-01

    Extracts of the pepper plant kava (Piper methysticum) are effective in alleviating anxiety in clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s) of the pharmacologically active constituents, kavalactones have not been established. γ-Aminobutyric acid type A receptors (GABAARs) are assumed to be the in vivo molecular target of kavalactones based on data from binding assays, but evidence in support of a direct interaction between kavalactones and GABAARs is scarce and equivocal. In this study, we characterised the functional properties of the major anxiolytic kavalactone, kavain at human recombinant α1β2, β2γ2L, αxβ2γ2L (x = 1, 2, 3 and 5), α1βxγ2L (x = 1, 2 and 3) and α4β2δ GABAARs expressed in Xenopus oocytes using the two-electrode voltage clamp technique. We found that kavain positively modulated all receptors regardless of the subunit composition, but the degree of enhancement was greater at α4β2δ than at α1β2γ2L GABAARs. The modulatory effect of kavain was unaffected by flumazenil, indicating that kavain did not enhance GABAARs via the classical benzodiazepine binding site. The β3N265M point mutation which has been previously shown to profoundly decrease anaesthetic sensitivity, also diminished kavain-mediated potentiation. To our knowledge, this study is the first report of the functional characteristics of a single kavalactone at distinct GABAAR subtypes, and presents the first experimental evidence in support of a direct interaction between a kavalactone and GABAARs. PMID:27332705

  18. A mitochondrial genome phylogeny of termites (Blattodea: Termitoidae): robust support for interfamilial relationships and molecular synapomorphies define major clades.

    PubMed

    Cameron, Stephen L; Lo, Nathan; Bourguignon, Thomas; Svenson, Gavin J; Evans, Theodore A

    2012-10-01

    Despite their ecological significance as decomposers and their evolutionary significance as the most speciose eusocial insect group outside the Hymenoptera, termite (Blattodea: Termitoidae or Isoptera) evolutionary relationships have yet to be well resolved. Previous morphological and molecular analyses strongly conflict at the family level and are marked by poor support for backbone nodes. A mitochondrial (mt) genome phylogeny of termites was produced to test relationships between the recognised termite families, improve nodal support and test the phylogenetic utility of rare genomic changes found in the termite mt genome. Complete mt genomes were sequenced for 7 of the 9 extant termite families with additional representatives of each of the two most speciose families Rhinotermitidae (3 of 7 subfamilies) and Termitidae (3 of 8 subfamilies). The mt genome of the well supported sister-group of termites, the subsocial cockroach Cryptocercus, was also sequenced. A highly supported tree of termite relationships was produced by all analytical methods and data treatment approaches, however the relationship of the termites+Cryptocercus clade to other cockroach lineages was highly affected by the strong nucleotide compositional bias found in termites relative to other dictyopterans. The phylogeny supports previously proposed suprafamilial termite lineages, the Euisoptera and Neoisoptera, a later derived Kalotermitidae as sister group of the Neoisoptera and a monophyletic clade of dampwood (Stolotermitidae, Archotermopsidae) and harvester termites (Hodotermitidae). In contrast to previous termite phylogenetic studies, nodal supports were very high for family-level relationships within termites. Two rare genomic changes in the mt genome control region were found to be molecular synapomorphies for major clades. An elongated stem-loop structure defined the clade Polyphagidae + (Cryptocercus+termites), and a further series of compensatory base changes in this stem-loop is

  19. Noninvasive inference of the molecular chemotactic response using bacterial trajectories.

    PubMed

    Masson, Jean-Baptiste; Voisinne, Guillaume; Wong-Ng, Jerome; Celani, Antonio; Vergassola, Massimo

    2012-01-31

    The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of Escherichia coli to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reconstructed from its response function to an impulse, which then controls the efficiency of bacterial motility. We introduce a method for measuring the impulse response function based on coupling microfluidic experiments and inference methods: The response function is inferred using Bayesian methods from the observed trajectories of bacteria swimming in microfluidically controlled chemical fields. The notable advantages are that the method is based on the bacterial swimming response, it is noninvasive, without any genetic and/or mechanical preparation, and assays the behavior of the whole flagella bundle. We exploit the inference method to measure responses to aspartate and α-methylaspartate--measured previously by other methods--as well as glucose, leucine, and serine. The response to the attractant glucose is shown to be biphasic and perfectly adapted, as for aspartate. The response to the attractant serine is shown to be biphasic yet imperfectly adapted, that is, the response function has a nonzero (positive) integral. The adaptation of the response to the repellent leucine is also imperfect, with the sign of the two phases inverted with respect to serine. The diversity in the bacterial population of the response function and its dependency upon the background concentration are quantified. PMID:22307649

  20. Physiological, biochemical and molecular responses of the potato (Solanum tuberosum L.) plant to moderately elevated temperature.

    PubMed

    Hancock, Robert D; Morris, Wayne L; Ducreux, Laurence J M; Morris, Jenny A; Usman, Muhammad; Verrall, Susan R; Fuller, John; Simpson, Craig G; Zhang, Runxuan; Hedley, Pete E; Taylor, Mark A

    2014-02-01

    Although significant work has been undertaken regarding the response of model and crop plants to heat shock during the acclimatory phase, few studies have examined the steady-state response to the mild heat stress encountered in temperate agriculture. In the present work, we therefore exposed tuberizing potato plants to mildly elevated temperatures (30/20 °C, day/night) for up to 5 weeks and compared tuber yield, physiological and biochemical responses, and leaf and tuber metabolomes and transcriptomes with plants grown under optimal conditions (22/16 °C). Growth at elevated temperature reduced tuber yield despite an increase in net foliar photosynthesis. This was associated with major shifts in leaf and tuber metabolite profiles, a significant decrease in leaf glutathione redox state and decreased starch synthesis in tubers. Furthermore, growth at elevated temperature had a profound impact on leaf and tuber transcript expression with large numbers of transcripts displaying a rhythmic oscillation at the higher growth temperature. RT-PCR revealed perturbation in the expression of circadian clock transcripts including StSP6A, previously identified as a tuberization signal. Our data indicate that potato plants grown at moderately elevated temperatures do not exhibit classic symptoms of abiotic stress but that tuber development responds via a diversity of biochemical and molecular signals.

  1. Determining molecular responses to environmental change in soybeans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As the global climate changes, plants will be challenged by environmental stresses that are more extreme and more frequent. The average yield loss due to environmental stresses is currently estimated to be more than 50% for major crop species and is the major limitation to world food production. The...

  2. The major low-molecular-weight heat shock protein in chloroplasts shows antigenic conservation among diverse higher plant species.

    PubMed

    Vierling, E; Harris, L M; Chen, Q

    1989-02-01

    Several plant species are known to synthesize low-molecular-weight nucleus-encoded heat shock proteins (HSPs) which localize to chloroplasts. DNA sequence analysis of chloroplast HSP cDNAs from pea (Pisum sativum) and soybean (Glycine max) has shown that the carboxyl-terminal halves of these proteins are homologous to low-molecular-weight HSPs from a wide range of eucaryotes (E. Vierling, R. T. Nagao, A. E. DeRocher, and L. M. Harris, EMBO J. 7:575-581, 1988). We used a pea cDNA to construct fusion proteins containing either the carboxyl-terminal heat shock domain or the amino-terminal domain of the chloroplast HSP. The fusion proteins were overexpressed in Escherichia coli and used to produce choloroplast HSP-specific polyclonal antibodies. The carboxyl-terminal antibodies recognized chloroplast HSP precursor proteins from pea and from three divergent plant species, Arabidopsis thaliana, petunia (Petunia hybrida), and maize (Zea mays). The amino-terminal antibodies recognized effectively only the pea precursor. When intact plants of each species were subjected to a heat stress regime mimicking field growth conditions, significant levels of the mature forms of the chloroplast HSPs accumulated in pea, A. thaliana, and maize. The levels of accumulated HSPs remained unchanged for 12 h following the stress treatment. We conclude that the synthesis of chloroplast-localized HSPs is an important component of the stree response in all higher plants and that chloroplast HSPs from dicotyledonous and monocotyledonous plants have a conserved carboxyl-terminal domain.

  3. Maximizing the dielectric response of molecular thin films via quantum chemical design.

    PubMed

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

    2014-12-23

    Developing high-capacitance organic gate dielectrics is critical for advances in electronic circuitry based on unconventional semiconductors. While high-dielectric constant molecular substances are known, the mechanism of dielectric response and the fundamental chemical design principles are not well understood. Using a plane-wave density functional theory formalism, we show that it is possible to map the atomic-scale dielectric profiles of molecule-based materials while capturing important bulk characteristics. For molecular films, this approach reveals how basic materials properties such as surface coverage density, molecular tilt angle, and π-system planarity can dramatically influence dielectric response. Additionally, relatively modest molecular backbone and substituent variations can be employed to substantially enhance film dielectric response. For dense surface coverages and proper molecular alignment, conjugated hydrocarbon chains can achieve dielectric constants of >8.0, more than 3 times that of analogous saturated chains, ∼2.5. However, this conjugation-related dielectric enhancement depends on proper molecular orientation and planarization, with enhancements up to 60% for proper molecular alignment with the applied field and an additional 30% for conformations such as coplanarity in extended π-systems. Conjugation length is not the only determinant of dielectric response, and appended polarizable high-Z substituents can increase molecular film response more than 2-fold, affording estimated capacitances of >9.0 μF/cm2. However, in large π-systems, polar substituent effects are substantially attenuated.

  4. Development of SRAP, SNP and multiplexed SCAR molecular markers for the major seed coat color gene in Brassica rapa L.

    PubMed

    Rahman, Mukhlesur; McVetty, Peter B E; Li, Genyi

    2007-11-01

    Seed coat color inheritance in B. rapa was studied in F(1), F(2), F(3), and BC(1) progenies from a cross of a Canadian brown-seeded variety 'SPAN' and a Bangladeshi yellow sarson variety 'BARI-6'. A pollen effect was found when the yellow sarson line was used as the maternal parent. Seed coat color segregated into brown, yellow-brown and bright yellow classes. Segregation was under digenic control where the brown or yellow-brown color was dominant over bright yellow seed coat color. A sequence related amplified polymorphism (SRAP) marker linked closely to a major seed coat color gene (Br1/br1) was developed. This dominant SRAP molecular marker was successfully converted into single nucleotide polymorphism (SNP) markers and sequence characterized amplification region (SCAR) markers after the extended flanking sequence of the SRAP was obtained with chromosome walking. In total, 24 SNPs were identified with more than 2-kb sequence. A 12-bp deletion allowed the development of a SCAR marker linked closely to the Br1 gene. Using the five-fluorescence dye set supplied by ABI, four labeled M13 primers were integrated with different SCAR primers to increase the throughput of SCAR marker detection. Using multiplexed SCAR markers targeting insertions and deletions in a genome shows great potential for marker assisted selection in plant breeding.

  5. Genomic, RNAseq, and molecular modeling evidence suggests that the major allergen domain in insects evolved from a homodimeric origin.

    PubMed

    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.

  6. Major Variations in HIV-1 Capsid Assembly Morphologies Involve Minor Variations in Molecular Structures of Structurally Ordered Protein Segments.

    PubMed

    Lu, Jun-Xia; Bayro, Marvin J; Tycko, Robert

    2016-06-17

    We present the results of solid state nuclear magnetic resonance (NMR) experiments on HIV-1 capsid protein (CA) assemblies with three different morphologies, namely wild-type CA (WT-CA) tubes with 35-60 nm diameters, planar sheets formed by the Arg(18)-Leu mutant (R18L-CA), and R18L-CA spheres with 20-100 nm diameters. The experiments are intended to elucidate molecular structural variations that underlie these variations in CA assembly morphology. We find that multidimensional solid state NMR spectra of (15)N,(13)C-labeled CA assemblies are remarkably similar for the three morphologies, with only small differences in (15)N and (13)C chemical shifts, no significant differences in NMR line widths, and few differences in the number of detectable NMR cross-peaks. Thus, the pronounced differences in morphology do not involve major differences in the conformations and identities of structurally ordered protein segments. Instead, morphological variations are attributable to variations in conformational distributions within disordered segments, which do not contribute to the solid state NMR spectra. Variations in solid state NMR signals from certain amino acid side chains are also observed, suggesting differences in the intermolecular dimerization interface between curved and planar CA lattices, as well as possible differences in intramolecular helix-helix packing. PMID:27129282

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

    PubMed Central

    Bailo, Begoña; Aguilera, María; Fuentes, Isabel; Carmena, David

    2015-01-01

    Background 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. Methods 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. Principal findings 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

  8. Integrating responsible conduct of research education into undergraduate biochemistry and molecular biology laboratory curricula.

    PubMed

    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 agencies offer useful templates for the introduction of RCR materials into courses worldwide. Many academic programs already offer courses or workshops in RCR for their graduate students and for undergraduate science majors and/or researchers. Introducing RCR into undergraduate biochemistry and molecular biology laboratory curricula is another, highly practical way that students can be exposed to these important topics. In fact, a strong argument can be made for integrating RCR into laboratory courses because these classes often introduce students to a scientific environment like that they might encounter in their careers after graduation. This article focuses on general strategies for incorporating explicit RCR education into biochemistry and molecular biology laboratory coursework using the topics suggested by NIH as a starting point.

  9. Molecular responses to moderate endurance exercise in skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. Dealing with the Challenges of Teaching Molecular Biophysics to Biochemistry Majors through an Heuristics-Based Approach

    ERIC Educational Resources Information Center

    Castanho, Miguel A. R. B.

    2002-01-01

    The main distinction between the overlapping fields of molecular biophysics and biochemistry resides in their different approaches to the same problems. Molecular biophysics makes more use of physical techniques and focuses on quantitative data. This difference encounters two difficult pedagogical challenges when teaching molecular biophysics to…

  11. Molecular communications between plant heat shock responses and disease resistance.

    PubMed

    Lee, Jae-Hoon; Yun, Hye Sup; Kwon, Chian

    2012-08-01

    As sessile, plants are continuously exposed to potential dangers including various abiotic stresses and pathogen attack. Although most studies focus on plant responses under an ideal condition to a specific stimulus, plants in nature must cope with a variety of stimuli at the same time. This indicates that it is critical for plants to fine-control distinct signaling pathways temporally and spatially for simultaneous and effective responses to various stresses. Global warming is currently a big issue threatening the future of humans. Reponses to high temperature affect many physiological processes in plants including growth and disease resistance, resulting in decrease of crop yield. Although plant heat stress and defense responses share important mediators such as calcium ions and heat shock proteins, it is thought that high temperature generally suppresses plant immunity. We therefore specifically discuss on interactions between plant heat and defense responses in this review hopefully for an integrated understanding of these responses in plants.

  12. Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

    PubMed

    DeLong, G Robert; Ritch, Chad R; Burch, Sherri

    2002-10-01

    One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

  13. Qualitative differences in the early immune response to live and killed Leishmania major: Implications for vaccination strategies against Leishmaniasis.

    PubMed

    Okwor, Ifeoma; Liu, Dong; Uzonna, Jude

    2009-04-28

    Recovery from natural or deliberate infection with Leishmania major leads to the development of lifelong immunity against rechallenge infections. In contrast, vaccination with killed parasites or defined leishmanial antigens generally induces only short-term protection. The reasons for this difference are currently not known but may be related to differences in the quality of the early immune responses to live and killed parasites. Here, we report that live and killed L. major parasites elicit comparable early inflammatory response as evidenced by influx and/or proliferation of cells in the draining lymph nodes (dLNs). In contrast, the early cytokine responses were qualitatively different. Cells from mice inoculated with killed parasites produced significantly more antigen-specific IL-4 and less IFN-gamma than those from mice injected with live parasites. Inclusion of CpG ODN into killed parasite preparations changed the early response to killed parasites from IL-4 to a predominantly IFN-gamma response, resulting in better protection following secondary high dose virulent L. major challenge. Interestingly, CpG-mediated enhancement of killed parasites-induced protection was short-lived and waned after 12 weeks. Taken together, these results suggest that the nature of primary immunity induced by killed and live parasites are qualitatively different and that these differences may account for the differential protection seen in mice following vaccination with live and killed parasites. They further suggest that modulating the early response with an appropriate adjuvant could enhance efficacy of killed parasite vaccines.

  14. The role of membrane ERα signaling in bone and other major estrogen responsive tissues

    PubMed Central

    Gustafsson, K. L.; Farman, H.; Henning, P.; Lionikaite, V.; Movérare-Skrtic, S.; Wu, J.; Ryberg, H.; Koskela, A.; Gustafsson, J.-Å.; Tuukkanen, J.; Levin, E. R.; Ohlsson, C.; Lagerquist, M. K.

    2016-01-01

    Estrogen receptor α (ERα) signaling leads to cellular responses in several tissues and in addition to nuclear ERα-mediated effects, membrane ERα (mERα) signaling may be of importance. To elucidate the significance, in vivo, of mERα signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERα to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERα signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40–70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERα (<35% reduction in estrogen response in NOER mice). In conclusion, mERα signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ERα actions may provide means to develop new selective estrogen receptor modulators with improved profiles. PMID:27388455

  15. Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib.

    PubMed

    Hughes, Timothy P; Lipton, Jeffrey H; Spector, Nelson; Cervantes, Francisco; Pasquini, Ricardo; Clementino, Nelma Cristina D; Dorlhiac Llacer, Pedro Enrique; Schwarer, Anthony P; Mahon, Francois-Xavier; Rea, Delphine; Branford, Susan; Purkayastha, Das; Collins, LaTonya; Szczudlo, Tomasz; Leber, Brian

    2014-07-31

    Patients in complete cytogenetic response (CCyR) with detectable BCR-ABL1 after ≥2 years on imatinib were randomized to nilotinib (400 mg twice daily, n = 104) or continued imatinib (n = 103) in the Evaluating Nilotinib Efficacy and Safety in clinical Trials-Complete Molecular Response (ENESTcmr) trial. By 1 and 2 years, confirmed undetectable BCR-ABL1 was achieved by 12.5% vs 5.8% (P = .108) and 22.1% vs 8.7% of patients in the nilotinib and imatinib arms, respectively (P = .0087). Among patients without molecular response 4.5 (BCR-ABL1(IS) ≤0.0032%; MR(4.5)) and those without major molecular response at study start, MR(4.5) by 2 years was achieved by 42.9% vs 20.8% and 29.2% vs 3.6% of patients in the nilotinib and imatinib arms, respectively. No patient in the nilotinib arm lost CCyR, vs 3 in the imatinib arm. Adverse events were more common in the nilotinib arm, as expected with the introduction of a new drug vs remaining on a well-tolerated drug. The safety profile of nilotinib was consistent with other reported studies. In summary, switching to nilotinib enabled more patients with chronic myeloid leukemia in chronic phase (CML-CP) to sustain lower levels of disease burden vs remaining on imatinib. This trial was registered at www.clinicaltrials.gov as #NCT00760877.

  16. Growth Responses of Plantago major L. ssp. pleiosperma (Pilger) to Changes in Mineral Supply : Evidence for Regulation by Cytokinins.

    PubMed

    Kuiper, D

    1988-07-01

    Plants of an inbred line of Plantago major ssp. pleiosperma were subjected to an alteration in mineral supply. Observed responses of growth rate and shoot to root ratio are thought to be induced by changes in endogenous cytokinin concentration and not by mineral concentration in plant tissue.

  17. Molecular mechanisms involved in initiation of the DNA damage response

    PubMed Central

    Barnum, Kevin J; O’Connell, Matthew J

    2015-01-01

    DNA is subject to a wide variety of damage. In order to maintain genomic integrity, cells must respond to this damage by activating repair and cell cycle checkpoint pathways. The initiating events in the DNA damage response entail recognition of the lesion and the assembly of DNA damage response complexes at the DNA. Here, we review what is known about these processes for various DNA damage pathways. PMID:27308403

  18. Abnormal loading of the major joints in knee osteoarthritis and the response to knee replacement.

    PubMed

    Metcalfe, Andrew; Stewart, Caroline; Postans, Neil; Barlow, David; Dodds, Alexander; Holt, Cathy; Whatling, Gemma; Roberts, Andrew

    2013-01-01

    Knee osteoarthritis is common and patients frequently complain that they are 'overloading' the joints of the opposite leg when they walk. However, it is unknown whether moments or co-contractions are abnormal in the unaffected joints of patients with single joint knee osteoarthritis, or how they change following treatment of the affected knee. Twenty patients with single joint medial compartment knee osteoarthritis were compared to 20 asymptomatic control subjects. Gait analysis was performed for normal level gait and surface EMG recordings of the medial and lateral quadriceps and hamstrings were used to investigate co-contraction. Patients were followed up 12 months post-operatively and the analysis was repeated. Results are presented for the first 14 patients who have attended follow-up. Pre-operatively, adduction moment impulses were elevated at both knees and the contra-lateral hip compared to controls. Co-contraction of hamstrings and quadriceps was elevated bilaterally. Post-operatively, moment waveforms returned to near-normal levels at the affected knee and co-contraction fell in the majority of patients. However, abnormalities persisted in the contra-lateral limb with partial or no recovery of both moment waveforms and co-contraction in the majority. Patients with knee osteoarthritis do experience abnormal loads of their major weight bearing joints bilaterally, and abnormalities persist despite treatment of the affected limb. Further treatment may be required if we are to protect the other major joints following joint arthroplasty.

  19. Molecular mechanisms responsible for hydrate anti-agglomerant performance.

    PubMed

    Phan, Anh; Bui, Tai; Acosta, Erick; Krishnamurthy, Pushkala; Striolo, Alberto

    2016-09-28

    Steered and equilibrium molecular dynamics simulations were employed to study the coalescence of a sI hydrate particle and a water droplet within a hydrocarbon mixture. The size of both the hydrate particle and the water droplet is comparable to that of the aqueous core in reverse micelles. The simulations were repeated in the presence of various quaternary ammonium chloride surfactants. We investigated the effects due to different groups on the quaternary head group (e.g. methyl vs. butyl groups), as well as different hydrophobic tail lengths (e.g. n-hexadecyl vs. n-dodecyl tails) on the surfactants' ability to prevent coalescence. Visual inspection of sequences of simulation snapshots indicates that when the water droplet is not covered by surfactants it is more likely to approach the hydrate particle, penetrate the protective surfactant film, reach the hydrate surface, and coalesce with the hydrate than when surfactants are present on both surfaces. Force-distance profiles obtained from steered molecular dynamics simulations and free energy profiles obtained from umbrella sampling suggest that surfactants with butyl tripods on the quaternary head group and hydrophobic tails with size similar to the solvent molecules can act as effective anti-agglomerants. These results qualitatively agree with macroscopic experimental observations. The simulation results provide additional insights, which could be useful in flow assurance applications: the butyl tripod provides adhesion between surfactants and hydrates; when the length of the surfactant tail is compatible with that of the hydrocarbon in the liquid phase a protective film can form on the hydrate; however, once a molecularly thin chain of water molecules forms through the anti-agglomerant film, connecting the water droplet and the hydrate, water flows to the hydrate and coalescence is inevitable. PMID:27436688

  20. Genetic variability and molecular responses of root penetration in cotton.

    PubMed

    Klueva; Joshi; Joshi; Wester; Zartman; Cantrell; Nguyen

    2000-06-12

    Compacted soils restrict root penetration hindering productivity. In this paper, genetic variability of cotton (Gossipium spp.) root capacity to penetrate hard soil layers and the patterns of gene expression during penetration event were investigated. To mimic hard soil layers, wax-petrolatum mixtures were used. Genetic variability among 27 cotton genotypes for the root capacity to penetrate wax-petrolatum disks of 500-700 g wax/kg of mixture was high indicating that breeding efforts targeted to improve this trait can be successful. In the root tips of a cotton strain with high root penetrating ability (G. hirsutum HS 200) which penetrated through wax-petrolatum disks (P), quantity of four polypeptides with molecular weights 35-66 kDa increased compared to those root tips which grew in the absence of mechanical impedance (NP). Differential display showed significant differences in the sets of mRNA expressed in P and NP roots. Out of a total of 917 cDNAs scored in the differential display experiment, 118 cDNAs, or 13%, were specific to P roots and hence could be associated with the root penetration event. Further detailed study of gene expression in penetrated roots will pinpoint molecular factors involved in root penetration ability in cotton. PMID:10773338

  1. Genetic variability and molecular responses of root penetration in cotton.

    PubMed

    Klueva; Joshi; Joshi; Wester; Zartman; Cantrell; Nguyen

    2000-06-12

    Compacted soils restrict root penetration hindering productivity. In this paper, genetic variability of cotton (Gossipium spp.) root capacity to penetrate hard soil layers and the patterns of gene expression during penetration event were investigated. To mimic hard soil layers, wax-petrolatum mixtures were used. Genetic variability among 27 cotton genotypes for the root capacity to penetrate wax-petrolatum disks of 500-700 g wax/kg of mixture was high indicating that breeding efforts targeted to improve this trait can be successful. In the root tips of a cotton strain with high root penetrating ability (G. hirsutum HS 200) which penetrated through wax-petrolatum disks (P), quantity of four polypeptides with molecular weights 35-66 kDa increased compared to those root tips which grew in the absence of mechanical impedance (NP). Differential display showed significant differences in the sets of mRNA expressed in P and NP roots. Out of a total of 917 cDNAs scored in the differential display experiment, 118 cDNAs, or 13%, were specific to P roots and hence could be associated with the root penetration event. Further detailed study of gene expression in penetrated roots will pinpoint molecular factors involved in root penetration ability in cotton.

  2. Molecular analyses of the principal components of response strength.

    PubMed Central

    Killeen, Peter R; Hall, Scott S; Reilly, Mark P; Kettle, Lauren C

    2002-01-01

    Killeen and Hall (2001) showed that a common factor called strength underlies the key dependent variables of response probability, latency, and rate, and that overall response rate is a good predictor of strength. In a search for the mechanisms that underlie those correlations, this article shows that (a) the probability of responding on a trial is a two-state Markov process; (b) latency and rate of responding can be described in terms of the probability and period of stochastic machines called clocked Bernoulli modules, and (c) one such machine, the refractory Poisson process, provides a functional relation between the probability of observing a response during any epoch and the rate of responding. This relation is one of proportionality at low rates and curvilinearity at higher rates. PMID:12216975

  3. Can we eliminate major tornadoes in Tornado Alley? — Response to the Comments

    NASA Astrophysics Data System (ADS)

    Tao, R.

    2014-11-01

    Dahl and Markowski are wrong and misleading to claim that the major tornadoes in USA Tornado Alley are not related to the collisions between northbound warm air flow and southbound cold air flow. In addition, they use incompressible and inviscid fluid model for atmosphere in their simulations about the interaction between air wind and the wall. Such approach ignores the basic physics and thus cannot reach any meaningful results. As air is compressible, the collision between the wind and wall will compress air, eventually lead the air density to decrease fast with the height and make the air flow stratified. The viscosity will produce wind shear, turbulent eddies and greatly reduce the wind's forwarding speed. Laboratory experiments and the Nature have all shown that hills with height about 300 m will not block winds completely to change the climate, but can effectively reduce the wind speed, weaken the air mass collisions and eliminate the major tornadoes. All these strongly support the theory that building east-west ranged walls of 300 m high and 50 m wide will eliminate major tornado threat in Tornado Alley.

  4. Responsive supramolecular gels constructed by crown ether based molecular recognition.

    PubMed

    Ge, Zhishen; Hu, Jinming; Huang, Feihe; Liu, Shiyong

    2009-01-01

    Responsive supramolecular gels were constructed from crown ether terminated four-arm star poly(epsilon-caprolactone) (PCL-DB24C8) and dibenzylammonium-terminated two-arm PCL-DBAS (see scheme), exploiting the formation of pseudorotaxane linkages between crown ether and ammonium moieties. The resultant supramolecular gels exhibit thermo- and pH-induced reversible gel-sol transition.

  5. Nuclear Cytoplasmic Trafficking of Proteins is a Major Response of Human Fibroblasts to Oxidative Stress

    PubMed Central

    Baqader, Noor O.; Radulovic, Marko; Crawford, Mark; Stoeber, Kai; Godovac-Zimmermann, Jasminka

    2014-01-01

    We have used a subcellular spatial razor approach based on LC–MS/MS-based proteomics with SILAC isotope labeling to determine changes in protein abundances in the nuclear and cytoplasmic compartments of human IMR90 fibroblasts subjected to mild oxidative stress. We show that response to mild tert-butyl hydrogen peroxide treatment includes redistribution between the nucleus and cytoplasm of numerous proteins not previously associated with oxidative stress. The 121 proteins with the most significant changes encompass proteins with known functions in a wide variety of subcellular locations and of cellular functional processes (transcription, signal transduction, autophagy, iron metabolism, TCA cycle, ATP synthesis) and are consistent with functional networks that are spatially dispersed across the cell. Both nuclear respiratory factor 2 and the proline regulatory axis appear to contribute to the cellular metabolic response. Proteins involved in iron metabolism or with iron/heme as a cofactor as well as mitochondrial proteins are prominent in the response. Evidence suggesting that nuclear import/export and vesicle-mediated protein transport contribute to the cellular response was obtained. We suggest that measurements of global changes in total cellular protein abundances need to be complemented with measurements of the dynamic subcellular spatial redistribution of proteins to obtain comprehensive pictures of cellular function. PMID:25133973

  6. A molecular pathway for CO₂ response in Arabidopsis guard cells.

    PubMed

    Tian, Wang; Hou, Congcong; Ren, Zhijie; Pan, Yajun; Jia, Jinjin; Zhang, Haiwen; Bai, Fenglin; Zhang, Peng; Zhu, Huifen; He, Yikun; Luo, Shenglian; Li, Legong; Luan, Sheng

    2015-01-20

    Increasing carbon dioxide (CO₂) levels in the atmosphere have caused global metabolic changes in diverse plant species. CO₂ is not only a carbon donor for photosynthesis but also an environmental signal that regulates stomatal movements and thereby controls plant-water relationships and carbon metabolism. However, the mechanism underlying CO₂ sensing in stomatal guard cells remains unclear. Here we report characterization of Arabidopsis RESISTANT TO HIGH CO₂ (RHC1), a MATE-type transporter that links elevated CO₂ concentration to repression of HT1, a protein kinase that negatively regulates CO₂-induced stomatal closing. We also show that HT1 phosphorylates and inactivates OST1, a kinase which is essential for the activation of the SLAC1 anion channel and stomatal closing. Combining genetic, biochemical and electrophysiological evidence, we reconstituted the molecular relay from CO₂ to SLAC1 activation, thus establishing a core pathway for CO₂ signalling in plant guard cells.

  7. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  8. Molecular identification, polymorphism, and expression analysis of major histocompatibility complex class IIA and B genes of turbot (Scophthalmus maximus).

    PubMed

    Zhang, Yu-Xi; Chen, Song-Lin

    2006-01-01

    Major histocompatibility complex (MHC) class II has a central role in the adaptive immune system by presenting foreign peptides to the T-cell receptor. The full lengths of MHC class II A and B cDNA were cloned from turbot by homology cloning and rapid amplification of cDNA ends polymerase chain reaction (RACE PCR), and genomic organization, molecular polymorphism, and expression of turbot class IIB gene were examined to study the function of class IIB gene in fish. The deduced amino acid sequence of turbot class II A (GenBank accession no.DQ001730) and turbot class IIB (GenBank accession no. DQ094170) had 69.8%, 67.6%, 65.5%, 59.2%, 54.5%, 52.8%, 46.2%, 46.6%, 28.3%, 28.5%, 22.2% identity and 71.5%, 70.7%, 67.1%, 68.4%, 46.7%, 53.5%, 46.7%, 50.0%, 25.2%, 29.2%, 27.6% identity with those of Japanese flounder, striped sea bass, red sea bream, cichlid, rainbow trout, Atlantic salmon, carp, zebrafish, nurse shark, mouse and human, respectively. Eleven class IIB alleles were identified from three turbot individuals. The amino acid sequence of turbot class IIB designated as Scma-DAB*0101 had 86.9%, 88.6%, 88.6%, 89.4%, 87.8%, 86.9%, 84.1%, 86.5%, 87.3%, 77.1%, and 86.9% identity with those of turbot class IIB 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (Scma-DAB*0201- Scma-DAB*1201), respectively. Six different class IIB alleles observed in a single individual may infer the existence of three loci at least. Semiquantitative reverse transcriptase PCR (RT-PCR) demonstrated that turbot class IIA and B were ubiquitously expressed in normal tissues. Challenge of turbot with pathogenic bacteria, Vibrio anguillarum, resulted in a significant decrease in the expression of MHC class IIB mRNA from 24 h to 48 h after infection in liver and head kidney, and a significant decrease from 24 h to 72 h after infection in spleen, followed by an increase after 96 h, respectively.

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

    NASA Astrophysics Data System (ADS)

    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.

  10. A 37-kilodalton glycoprotein of Babesia divergens is a major component of a protective fraction containing low-molecular-mass culture-derived exoantigens.

    PubMed

    Carcy, B; Precigout, E; Valentin, A; Gorenflot, A; Schrevel, J

    1995-03-01

    The supernatants of in vitro cultures of Babesia divergens Rouen 1987 in human erythrocytes, obtained by using a semidefined medium based on human high-density lipoproteins, were fractionated by gel filtration chromatography into four fractions, F1 to F4. The crude supernatant as well as each fraction adjuvanted with Quil-A protected gerbils from mortality due to a homologous infectious challenge. Analysis of the humoral response of the 10 protected gerbils with fraction F4, containing major proteins with molecular masses lower than 50 kDa, showed that a few antigens (from 50 to 17 kDa) could be important candidates for an improved vaccine against B. divergens babesiosis. As an immunodominant response was directed against the 37-kDa antigen (Bd37) in two different B. divergens strains tested, a polyclonal antibody directed against Bd37 was produced in a rabbit. In an immunofluorescence assay, the anti-Bd37 antiserum strongly labelled small internal vesicles of the merozoites and the cell surface was diffusely labelled after fixation, whereas on live merozoites, this labelling was not observed. [3H]glucosamine-radiolabelling experiments demonstrate that Bd37 is a glycoprotein. The Bd37 protein can also be labelled with [14C]palmitate but not with [3H]myristic acid. In Triton X-114 temperature phase partitioning of B. divergens-infected erythrocyte extracts, Bd37 was exclusively found into the detergent phase, indicating that the palmitoylated Bd37 protein was in the membrane fraction. In the in vitro supernatant, the glycoprotein Bd37 was found in a nonpalmitoylated form, indicating excretion and/or release of the glycoprotein from the merozoite.

  11. Molecular and biochemical responses of Volvox carteri to oxidative stress

    NASA Astrophysics Data System (ADS)

    Lingappa, U.; Rankin-Gee, E. K.; Lera, M.; Bebour, B.; Marcu, O.

    2014-03-01

    Understanding the intracellular response to environmental stresses is a key aspect to understanding the limits of habitability for life as we know it. A wide range of relevant stressors, from heat shock to radiation, result in the intracellular production of reactive oxygen species (ROS). ROS are used physiologically as signaling molecules to cause changes in gene expression and metabolism. However, ROS, including superoxide (O2-) and peroxides, are also highly reactive molecules that cause oxidative damage to proteins, lipids and DNA. Here we studied stress response in the multicellular, eukaryotic green alga Volvox carteri, after exposure to heat shock conditions. We show that the ROS response to heat stress is paralleled by changes in photosynthetic metabolism, antioxidant enzyme activity and gene expression, and fluctuations in the elemental composition of cells. Metabolism, as measured by pulse amplitude modulated (PAM) fluorometry over two hours of heat stress, showed a linear decrease in the photosynthetic efficiency of Volvox. ROS quantification uncovered an increase in ROS in the culture medium, paralleled by a decrease in ROS within the Volvox colonies, suggesting an export mechanism is utilized to mitigate stress. Enzyme kinetics indicated an increase in superoxide dismutase (SOD) activity over the heat stress timecourse. Using X-ray fluorescence (XRF) at the Stanford Synchrotron Radiation Lightsource, we show that these changes coincide with cell-specific import/export and intracellular redistribution of transition elements and halides, suggesting that the cellular metallome is also engaged in mediating oxidative stress in Volvox.

  12. Shared and novel molecular responses of mandarin to drought.

    PubMed

    Gimeno, Jacinta; Gadea, José; Forment, Javier; Pérez-Valle, Jorge; Santiago, Julia; Martínez-Godoy, María A; Yenush, Lynne; Bellés, José M; Brumós, Javier; Colmenero-Flores, José M; Talón, Manuel; Serrano, Ramón

    2009-07-01

    Drought is the most important stress experienced by citrus crops. A citrus cDNA microarray of about 6.000 genes has been utilized to identify transcriptomic responses of mandarin to water stress. As observed in other plant species challenged with drought stress, key genes for lysine catabolism, proline and raffinose synthesis, hydrogen peroxide reduction, vacuolar malate transport, RCI2 proteolipids and defence proteins such as osmotin, dehydrins and heat-shock proteins are induced in mandarin. Also, some aquaporin genes are repressed. The osmolyte raffinose could be detected in stressed roots while the dehydrin COR15 protein only accumulated in stressed leaves but not in roots. Novel drought responses in mandarin include the induction of genes encoding a new miraculin isoform, chloroplast beta-carotene hydroxylase, oleoyl desaturase, ribosomal protein RPS13A and protein kinase CTR1. These results suggest that drought tolerance in citrus may benefit from inhibition of proteolysis, activation of zeaxanthin and linolenoyl synthesis, reinforcement of ribosomal structure and down-regulation of the ethylene response. PMID:19290483

  13. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs. PMID:23965842

  14. Functional responses and molecular mechanisms involved in histone-mediated platelet activation.

    PubMed

    Carestia, A; Rivadeneyra, L; Romaniuk, M A; Fondevila, C; Negrotto, S; Schattner, M

    2013-11-01

    Histones are highly alkaline proteins found in cell nuclei and they can be released by either dying or inflammatory cells. The recent observations that histones are major components of neutrophil extracellular traps and promote platelet aggregation and platelet-dependent thrombin generation have shown that these proteins are potent prothrombotic molecules. Because the mechanism(s) of platelet activation by histones are not completely understood, we explored the ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to induce platelet activation as well as the possible molecular mechanisms involved. All histones were substrates for platelet adhesion and spreading and triggered fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and phosphatidylserine (PS) exposure and the formation of platelet-leukocyte aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding, P-selectin and PS exposure and the formation of mixed aggregates were potentiated by thrombin. Histones induced the activation of ERK, Akt, p38 and NFκB. Accordingly, histone-induced platelet activation was significantly impaired by pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002), p38 (SB 203580) and NFκB (BAY 11-7082 and Ro 106-9920). Preincubation of platelets with either aspirin or dexamethasone markedly decreased fibrinogen binding and the adhesion mediated by histones without affecting P-selectin exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and H2B, were partially mediated through interaction with Toll-like receptors -2 and -4. Our data identify histones as important triggers of haemostatic and proinflammatory platelet responses, and only haemostatic responses are partially inhibited by anti-inflammatory drugs.

  15. [Regulation of Yersinia pseudotuberculosis major porin expression in response to antibiotic stress].

    PubMed

    Bystritskaia, E P; Stenkova, A M; Portniagina, O Iu; Rakin, A V; Rasskazov, V A; Isaeva, M P

    2014-01-01

    The OmpF porin gene expression in Yersinia pseudotuberculosis in response to antibiotics of two different classes (kanamycin and nalidixic acid) was analyzed using quantitative PCR and a fluorescence reporter system. Both antibiotics downregulated the expression of the ompF gene. The nalidixic acid significantly reduced ompF expression, while kanamycin, for which porins are considered to be an alternative transport route, only slightly reduced the ompF level.

  16. [Regulation of Yersinia pseudotuberculosis major porin expression in response to antibiotic stress].

    PubMed

    Bystritskaia, E P; Stenkova, A M; Portniagina, O Iu; Rakin, A V; Rasskazov, V A; Isaeva, M P

    2014-01-01

    The OmpF porin gene expression in Yersinia pseudotuberculosis in response to antibiotics of two different classes (kanamycin and nalidixic acid) was analyzed using quantitative PCR and a fluorescence reporter system. Both antibiotics downregulated the expression of the ompF gene. The nalidixic acid significantly reduced ompF expression, while kanamycin, for which porins are considered to be an alternative transport route, only slightly reduced the ompF level. PMID:25080814

  17. Regulatory coordination between two major intracellular homeostatic systems: heat shock response and autophagy.

    PubMed

    Dokladny, Karol; Zuhl, Micah Nathaniel; Mandell, Michael; Bhattacharya, Dhruva; Schneider, Suzanne; Deretic, Vojo; Moseley, Pope Lloyd

    2013-05-24

    The eukaryotic cell depends on multitiered homeostatic systems ensuring maintenance of proteostasis, organellar integrity, function and turnover, and overall cellular viability. At the two opposite ends of the homeostatic system spectrum are heat shock response and autophagy. Here, we tested whether there are interactions between these homeostatic systems, one universally operational in all prokaryotic and eukaryotic cells, and the other one (autophagy) is limited to eukaryotes. We found that heat shock response regulates autophagy. The interaction between the two systems was demonstrated by testing the role of HSF-1, the central regulator of heat shock gene expression. Knockdown of HSF-1 increased the LC3 lipidation associated with formation of autophagosomal organelles, whereas depletion of HSF-1 potentiated both starvation- and rapamycin-induced autophagy. HSP70 expression but not expression of its ATPase mutant inhibited starvation or rapamycin-induced autophagy. We also show that exercise induces autophagy in humans. As predicted by our in vitro studies, glutamine supplementation as a conditioning stimulus prior to exercise significantly increased HSP70 protein expression and prevented the expected exercise induction of autophagy. Our data demonstrate for the first time that heat shock response, from the top of its regulatory cascade (HSF-1) down to the execution stages delivered by HSP70, controls autophagy thus connecting and coordinating the two extreme ends of the homeostatic systems in the eukaryotic cell. PMID:23576438

  18. Exercise under hot conditions: a major threat to the immune response?

    PubMed

    Shephard, R J

    2002-09-01

    It seems likely that the disturbances of immune response induced by prolonged competitive exercise are exacerbated if athletes also face the stress of hot environmental conditions. We have investigated this question by manipulating the exercise-induced increases of body temperature in a climatic chamber and by submersion of exercisers in a large water-bath. Hot conditions increase the stress of a given bout of exercise, as assessed by personal perceptions, objective (heart rate variability) measures of autonomic nerve balance, and the secretion of "stress" hormones, with a parallel increase in effects upon critical lymphocyte subsets. Changes in the immune response show substantial correlations with plasma concentrations not only of epinephrine (which modulates the adhesiveness of peripherally sequestered lymphocytes), but also with norepinephrine. The latter hormone may mobilize leukocytes from the spleen and lymph glands, or it may act by increasing cardiac output and thus intravascular shear forces. Given the cumulative impact of various environmental stressors upon the immune system, every effort should be made to minimize the athlete's exposure to stresses other than the exercise to be performed. In some circumstances, the use of medications to reduce the overall stress response may also be warranted. PMID:12094129

  19. The host response and molecular pathogenesis associated with respiratory syncytial virus infection

    PubMed Central

    Oshansky, Christine M; Zhang, Wenliang; Moore, Elizabeth; Tripp, Ralph A

    2009-01-01

    Since the isolation of respiratory syncytial virus (RSV) in 1956, its significance as an important human pathogen in infants, the elderly and the immunocompromised has been established. Many important mechanisms contributing to RSV infection, replication and disease pathogenesis have been uncovered; however, there is still insufficient knowledge in these and related areas, which must be addressed to facilitate the development of safe and effective vaccines and therapeutic treatments. A better understanding of the molecular pathogenesis of RSV infection, particularly the host-cell response and transcription profiles to RSV infection, is required to advance disease intervention strategies. Substantial information is accumulating regarding how RSV proteins modulate molecular signaling and regulation of cytokine and chemokine responses to infection, molecular signals regulating programmed cell death, and innate and adaptive immune responses to infection. This review discusses RSV manipulation of the host response to infection and related disease pathogenesis. PMID:19327115

  20. The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness.

    PubMed

    Ouni, M; Belot, M P; Castell, A L; Fradin, D; Bougnères, P

    2016-02-01

    Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration. For example, variability in CG-137 methylation contributes 25% to variance of growth response to GH. Methylation of CGs in the P2 promoter is negatively associated with the increased transcriptional activity of P2 promoter in patients' mononuclear blood cells following GH administration. Our observation indicates that epigenetics is a major determinant of GH signaling (physiology) and of individual responsiveness to GH treatment (pharmacoepigenetics). PMID:25869012

  1. Characterizations of Three Major Cysteine Sensors of Keap1 in Stress Response.

    PubMed

    Saito, Ryota; Suzuki, Takafumi; Hiramoto, Keiichiro; Asami, Soichiro; Naganuma, Eriko; Suda, Hiromi; Iso, Tatsuro; Yamamoto, Hirotaka; Morita, Masanobu; Baird, Liam; Furusawa, Yuki; Negishi, Takaaki; Ichinose, Masakazu; Yamamoto, Masayuki

    2015-11-02

    The Keap1-Nrf2 system plays a central role in cytoprotection against electrophilic/oxidative stresses. Although Cys151, Cys273, and Cys288 of Keap1 are major sensor cysteine residues for detecting these stresses, it has not been technically feasible to evaluate the functionality of Cys273 or Cys288, since Keap1 mutants that harbor substitutions in these residues and maintain the ability to repress Nrf2 accumulation do not exist. To overcome this problem, we systematically introduced amino acid substitutions into Cys273/Cys288 and finally identified Cys273Trp and Cys288Glu mutations that do not affect Keap1's ability to repress Nrf2 accumulation. Utilizing these Keap1 mutants, we generated stable murine embryonic fibroblast (MEF) cell lines and knock-in mouse lines. Our analyses with the MEFs and peritoneal macrophages from the knock-in mice revealed that three major cysteine residues, Cys151, Cys273, and Cys288, individually and/or redundantly act as sensors. Based on the functional necessity of these three cysteine residues, we categorized chemical inducers of Nrf2 into four classes. Class I and II utilizes Cys151 and Cys288, respectively, while class III requires all three residues (Cys151/Cys273/Cys288), while class IV inducers function independently of all three of these cysteine residues. This study thus demonstrates that Keap1 utilizes multiple cysteine residues specifically and/or collaboratively as sensors for the detection of a wide range of environmental stresses.

  2. River responses to the 2010 major eruption of the Merapi volcano, central Java, Indonesia

    NASA Astrophysics Data System (ADS)

    Gob, Frédéric; Gautier, Emmanuèle; Virmoux, Clément; Grancher, Delphine; Tamisier, Vincent; Primanda, Kiki Widyaputra; Wibowo, Sandy Budi; Sarrazin, Caroline; de Belizal, Edouard; Ville, Anouk; Lavigne, Franck

    2016-11-01

    This study examines the fluvial readjustment of a Javanese river impacted by the major eruption of the Merapi volcano (Indonesia) in October and November 2010. The basin of the Opak River, located on the southern flank of the Merapi, was subject to substantial sediment input related to massive pyroclastic deposits that were remobilized by numerous lahars during the year after the eruption. Two study sites were equipped in order to evaluate the morphodynamic evolution of the riverbed of the Opak River. Topographic surveys, bedload particle marking, and suspended sediment sampling revealed an important sediment mobilization during efficient flash floods. Surprisingly, no bed aggradation related to the progradation of a sediment wave was observed. Two years after the eruptive event, marked bed incision was observed. The Opak River readjustment differs from that of other fluvial systems affected by massive eruptions in two ways. Firstly, local population extracted the sand and blocks injected by the eruption as they represent a valuable economic resource. Secondly, several dams trapped the major part of the sediment load remobilized by lahars.

  3. Personality disorder comorbidity with major depression and response to treatment with sertraline or citalopram.

    PubMed

    Ekselius, L; von Knorring, L

    1998-09-01

    The purpose of this study was to investigate the frequency of DSM-III-R personality disorders in depressed patients treated in primary care, and to examine the effect of sertraline or citalopram on the diagnosis of personality disorders. A total of 308 patients with a major depressive disorder were assessed with the Swedish version of the Structured Clinical Interview for Personality Disorders (SCID) screen questionnaire, before and after 24 weeks double-blind treatment with sertraline (50-150 mg/day) or citalopram (20-60 mg/day). Following treatment, significant reductions in the frequency of paranoid, borderline, avoidant and dependent personality disorder diagnoses were seen in both treatment groups. When the personality disorders were analysed as continuous, dimensional personality traits significant reductions were seen for most personality categories. To elucidate if the observed reductions in personality disorder criteria could be explained by the improvement in depressive symptomatology, a series of multiple regressions were made. Reduction of depression scores was of some importance for the changes in most personality disorders. However, the multiple R never exceeded 0.24 (cluster C). Type of drug was of importance only as concerns obsessive-compulsive personality disorder. Overall, the results suggest that sertraline and citalopram may be beneficial in the treatment of certain personality disorder traits in patients with major depressive disorders.

  4. Decipher the Molecular Response of Plant Single Cell Types to Environmental Stresses

    SciTech Connect

    Nourbakhsh-Rey, Mehrnoush; Libault, Marc

    2016-01-01

    The analysis of the molecular response of entire plants or organs to environmental stresses suffers from the cellular complexity of the samples used. Specifically, this cellular complexity masks cell-specific responses to environmental stresses and logically leads to the dilution of the molecular changes occurring in each cell type composing the tissue/organ/plant in response to the stress. Therefore, to generate a more accurate picture of these responses, scientists are focusing on plant single cell type approaches. Several cell types are now considered as models such as the pollen, the trichomes, the cotton fiber, various root cell types including the root hair cell, and the guard cell of stomata. Among them, several have been used to characterize plant response to abiotic and biotic stresses. Lastly, in this review, we are describing the various -omic studies performed on these different plant single cell type models to better understand plant cell response to biotic and abiotic stresses.

  5. Decipher the Molecular Response of Plant Single Cell Types to Environmental Stresses

    PubMed Central

    2016-01-01

    The analysis of the molecular response of entire plants or organs to environmental stresses suffers from the cellular complexity of the samples used. Specifically, this cellular complexity masks cell-specific responses to environmental stresses and logically leads to the dilution of the molecular changes occurring in each cell type composing the tissue/organ/plant in response to the stress. Therefore, to generate a more accurate picture of these responses, scientists are focusing on plant single cell type approaches. Several cell types are now considered as models such as the pollen, the trichomes, the cotton fiber, various root cell types including the root hair cell, and the guard cell of stomata. Among them, several have been used to characterize plant response to abiotic and biotic stresses. In this review, we are describing the various -omic studies performed on these different plant single cell type models to better understand plant cell response to biotic and abiotic stresses. PMID:27088086

  6. Decipher the Molecular Response of Plant Single Cell Types to Environmental Stresses.

    PubMed

    Nourbakhsh-Rey, Mehrnoush; Libault, Marc

    2016-01-01

    The analysis of the molecular response of entire plants or organs to environmental stresses suffers from the cellular complexity of the samples used. Specifically, this cellular complexity masks cell-specific responses to environmental stresses and logically leads to the dilution of the molecular changes occurring in each cell type composing the tissue/organ/plant in response to the stress. Therefore, to generate a more accurate picture of these responses, scientists are focusing on plant single cell type approaches. Several cell types are now considered as models such as the pollen, the trichomes, the cotton fiber, various root cell types including the root hair cell, and the guard cell of stomata. Among them, several have been used to characterize plant response to abiotic and biotic stresses. In this review, we are describing the various -omic studies performed on these different plant single cell type models to better understand plant cell response to biotic and abiotic stresses. PMID:27088086

  7. A Molecular Framework for Tunable Functional Response of Programmable Polyesters

    NASA Astrophysics Data System (ADS)

    Jha, Kshitij C.; Joy, Abraham; Tsige, Mesfin

    All-atom molecular dynamics (MD) simulations, using the OPLS force field, were carried out on a library of multifunctional polyesters with peptide-like functional pendant groups. The polyesters are structural peptidomimetics and can be utilized for applications in sensing, and separation, and as biomedical scaffolds. The modular design of the polyesters affords a range of hydrophilic and hydrophobic behavior. We used MD to quantify the hydrogen bond dynamics, end-to-end distance, and radii of gyration with changes in side group functionality, concentration, and temperature. We discerned trends for the physical behavior of polyesters with change in nature and ratio of the side groups. We also observed functional assembly for dissimilar polyesters, and correlated the assembly to the affinity of side groups. The trends in physical behavior and dissimilar assembly can be mined for iterative design towards programmatic assembly of the modular multifunctional polyesters under study. This work was made possible by funding from the ACS Petroleum Research Fund (ACS PRF 54801- ND5).

  8. Acoustic response of cemented granular sedimentary rocks: molecular dynamics modeling.

    PubMed

    García, Xavier; Medina, Ernesto

    2007-06-01

    The effect of cementation processes on the acoustical properties of sands is studied via molecular dynamics simulation methods. We propose numerical methods where the initial uncemented sand is built by simulating the settling process of sediments. Uncemented samples of different porosity are considered by emulating natural mechanical compaction of sediments due to overburden. Cementation is considered through a particle-based model that captures the underlying physics behind the process. In our simulations, we consider samples with different degrees of compaction and cementing materials with distinct elastic properties. The microstructure of cemented sands is taken into account while adding cement at specific locations within the pores, such as grain-to-grain contacts. Results show that the acoustical properties of cemented sands are strongly dependent on the amount of cement, its stiffness relative to the hosting medium, and its location within the pores. Simulation results are in good correspondence with available experimental data and compare favorably with some theoretical predictions for the sound velocity within a range of cement saturation, porosity, and confining pressure.

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

    PubMed Central

    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

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

    PubMed Central

    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.

    2015-01-01

    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 may affect a woman's reproductive health, including her risk of acquiring HIV. PMID:25992865

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

    SciTech Connect

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

    1985-10-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Molecular signatures in response to Isoliquiritigenin in lymphoblastoid cell lines

    SciTech Connect

    Lee, Jae-Eun; Hong, Eun-Jung; Nam, Hye-Young; Hwang, Meeyul; Kim, Ji-Hyun; Han, Bok-Ghee; Jeon, Jae-Pil

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer We identified the inhibitory effect of ISL on cell proliferation of LCLs. Black-Right-Pointing-Pointer We found ISL-induced genes and miRNAs through microarray approach. Black-Right-Pointing-Pointer ISL-treated LCLs represented gene expression changes in cell cycle and p53 pathway. Black-Right-Pointing-Pointer We revealed 12 putative mRNA-miRNA functional pairs associated with ISL effect. -- Abstract: Isoliquiritigenin (ISL) has been known to induce cell cycle arrest and apoptosis of various cancer cells. However, genetic factors regulating ISL effects remain unclear. The aim of this study was to identify the molecular signatures involved in ISL-induced cell death of EBV-transformed lymphoblastoid cell lines (LCLs) using microarray analyses. For gene expression and microRNA (miRNA) microarray experiments, each of 12 LCL strains was independently treated with ISL or DMSO as a vehicle control for a day prior to total RNA extraction. ISL treatment inhibited cell proliferation of LCLs in a dose-dependent manner. Microarray analysis showed that ISL-treated LCLs represented gene expression changes in cell cycle and p53 signaling pathway, having a potential as regulators in LCL survival and sensitivity to ISL-induced cytotoxicity. In addition, 36 miRNAs including five miRNAs with unknown functions were differentially expressed in ISL-treated LCLs. The integrative analysis of miRNA and gene expression profiles revealed 12 putative mRNA-miRNA functional pairs. Among them, miR-1207-5p and miR-575 were negatively correlated with p53 pathway- and cell cycle-associated genes, respectively. In conclusion, our study suggests that miRNAs play an important role in ISL-induced cytotoxicity in LCLs by targeting signaling pathways including p53 pathway and cell cycle.

  14. Marine molluscs in environmental monitoring. I. Cellular and molecular responses

    NASA Astrophysics Data System (ADS)

    Bresler, Vladimir; Abelson, Avigdor; Fishelson, Lev; Feldstein, Tamar; Rosenfeld, Michael; Mokady, Ofer

    2003-10-01

    levels of biological organization—the molecular and cellular level—the parameters measured may have the capacity not only for biomonitoring environmental quality, but also for early warning.

  15. p38MAPK: stress responses from molecular mechanisms to therapeutics

    PubMed Central

    Coulthard, Lydia R.; White, Danielle E.; Jones, Dominic L.; McDermott, Michael F.; Burchill, Susan A.

    2010-01-01

    The p38MAPK protein kinases affect a variety of intracellular responses, with well-recognized roles in inflammation, cell-cycle regulation, cell death, development, differentiation, senescence and tumorigenesis. In this review, we examine the regulatory and effector components of this pathway, focusing on their emerging roles in biological processes involved in different pathologies. We summarize how this pathway has been exploited for the development of therapeutics and discuss the potential obstacles of targeting this promiscuous protein kinase pathway for the treatment of different diseases. Furthermore, we discuss how the p38MAPK pathway might be best exploited for the development of more effective therapeutics with minimal side effects in a range of specific disease settings. PMID:19665431

  16. Chiral Molecular Optical Response to Nano-Shaped Light

    NASA Astrophysics Data System (ADS)

    Saurabh, Prasoon; Chernyak, Vladimir; Rouxel, Jeremy; Mukamel, Shaul

    Chiral linear optical signals are an important spectroscopic tool for biomolecules and chemical sensing applications. Exact expressions are derived which express these signals as a convolution of a non-local linear susceptibility of matter with a non-local intrinsic property of the electric field. The chiral response can be enhanced and optimized using nano-optical fields with strong spatial variation. The approach is based on a gauge invariant calculation using the minimal coupling Hamiltonian. The multipolar expansion is avoided and all multipoles are naturally incorporated. We apply these expression to achiral (planar) and chiral (dihedral angle of 45°) bi-phenyl as a physically intuitive illustration. The support of National Science Foundation (Grant No. CHE-1361516) and the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U.S. Dept. of Energy (award # DE-FG02-4ER15571).

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

    SciTech Connect

    Hoover, W.G.

    1980-05-28

    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.

  18. T cell proliferative responses to molecular fractions of periodontopathic bacteria.

    PubMed Central

    Ivanyi, L; Newman, H N; Marsh, P D

    1991-01-01

    Soluble antigenic preparations of Veillonella parvula and Bacteroides gingivalis were separated by SDS-PAGE and used after electroblotting and solubilization for in vitro lymphocyte stimulation in 13 patients with severe periodontitis and 12 controls. The cellular responses of controls and patients to V. parvula antigens were represented by four main proliferation-inducing fractions with 74-66, 52-46, 22-19 and 12 kD mol. wt. These fractions induced slightly enhanced DNA synthesis in lymphocytes from eight patients who failed to respond to whole antigenic extract. Lymphocyte samples from Veillonella whole extract unresponsive patients were also examined for in vitro proliferation by B. gingivalis fractions. Almost all stimulatory activities could be classified into five regions of 84-74, 35-31, 28-25, 17-15 and 12 kD. PMID:1988218

  19. Molecular Structure of Physiologically-Responsive Hydrogels Controls Diffusive Behavior

    PubMed Central

    Carr, Daniel A.; Peppas, Nicholas A.

    2011-01-01

    Summary Polymeric networks and the ensuing hydrogels of methacrylic acid and N-vinyl pyrrolidone were successfully synthesized using a UV-initiated free radical polymerization and characterized to assess their applicability as carriers for directed drug delivery. FT-IR spectroscopy revealed shifts in peak absorbances that indicated the presence of hydrogen bonding complexes between functional groups, while SEM imaging showed that the different comonomers affect the surface morphology of the microparticles. Dynamic pH swelling studies demonstrated the pH responsiveness of the carriers in gastric and intestinal conditions and revealed that systems containing higher concentrations of methacrylic acid experienced the highest degree of hydrogen bonding complexation in gastric conditions. The presence of NVP in the systems enhanced swelling. Equilibrium swelling studies revealed that the mesh size was sufficiently large to allow drug diffusion across the networks. PMID:19016502

  20. Multifaceted responses to two major parasites in the honey bee (Apis mellifera).

    PubMed

    Wagoner, Kaira M; Boncristiani, Humberto F; Rueppell, Olav

    2013-01-01

    The recent declines in managed honey bee populations are of scientific, ecological and economic concern, and are partially attributed to honey bee parasites and related disease. McDonnell et al. investigate behavioral, chemical and neurogenomic effects of parasitization by the ectoparasite Varroa destructor and the endoparasite Nosema ceranae. The study reveals important links between underlying mechanisms of immunity and parasitization in social insects by demonstrating that chemical signals and neurogenomic states are significantly different between parasitized and non-parasitized honey bees, and that neurogenomic states are partially conserved between bees infected with distinct parasites. However the study does not reveal whether differences measured are primarily the result of adaptive host responses or of manipulation of the honey bee host by the parasites and/or confounding viral loads of parasitized individuals. Questions answered and raised by McDonnell et al. will lead to an improved understanding of honey bee health and, more generally, host-parasite interactions.

  1. Evaluation of severe accident risks: Quantification of major input parameters. Experts` determination of structural response issues

    SciTech Connect

    Breeding, R.J.; Harper, F.T.; Brown, T.D.; Gregory, J.J.; Payne, A.C.; Gorham, E.D.; Murfin, W.; Amos, C.N.

    1992-03-01

    In support of the Nuclear Regulatory Commission`s (NRC`s) assessment of the risk from severe accidents at commercial nuclear power plants in the US reported in NUREG-1150, the Severe Accident Risk Reduction Program (SAARP) has completed a revised calculation of the risk to the general public from severe accidents at five nuclear power plants: Surry, Sequoyah, Zion, Peach Bottom, and Grand Gulf. The emphasis in this risk analysis was not on determining a ``so-called`` point estimate of risk. Rather, it was to determine the distribution of risk, and to discover the uncertainties that account for the breadth of this distribution. Off-site risk initiation by events, both internal to the power station and external to the power station were assessed. Much of the important input to the logic models was generated by expert panels. This document presents the distributions and the rationale supporting the distributions for the questions posed to the Structural Response Panel.

  2. Multifaceted responses to two major parasites in the honey bee (Apis mellifera)

    PubMed Central

    2013-01-01

    The recent declines in managed honey bee populations are of scientific, ecological and economic concern, and are partially attributed to honey bee parasites and related disease. McDonnell et al. investigate behavioral, chemical and neurogenomic effects of parasitization by the ectoparasite Varroa destructor and the endoparasite Nosema ceranae. The study reveals important links between underlying mechanisms of immunity and parasitization in social insects by demonstrating that chemical signals and neurogenomic states are significantly different between parasitized and non-parasitized honey bees, and that neurogenomic states are partially conserved between bees infected with distinct parasites. However the study does not reveal whether differences measured are primarily the result of adaptive host responses or of manipulation of the honey bee host by the parasites and/or confounding viral loads of parasitized individuals. Questions answered and raised by McDonnell et al. will lead to an improved understanding of honey bee health and, more generally, host-parasite interactions. PMID:23870063

  3. The FLC-like gene BvFL1 is not a major regulator of vernalization response in biennial beets

    PubMed Central

    Vogt, Sebastian H.; Weyens, Guy; Lefèbvre, Marc; Bork, Bettina; Schechert, Axel; Müller, Andreas E.

    2014-01-01

    Many plant species in temperate climate regions require vernalization over winter to initiate flowering. Flowering Locus C (FLC) and FLC-like genes are key regulators of vernalization requirement and growth habit in winter-annual and perennial Brassicaceae. In the biennial crop species Beta vulgaris ssp. vulgaris in the evolutionarily distant Caryophyllales clade of core eudicots growth habit and bolting time are controlled by the vernalization and photoperiod response gene BTC1 and the downstream BvFT1-BvFT2 module. B. vulgaris also contains a vernalization-responsive FLC homolog (BvFL1). Here, to further elucidate the regulation of vernalization response and growth habit in beet, we functionally characterized BvFL1 by RNAi and over-expression in transgenic plants. BvFL1 RNAi neither eliminated the requirement for vernalization of biennial beets nor had a major effect on bolting time after vernalization. Over-expression of BvFL1 resulted in a moderate late-bolting phenotype, with bolting after vernalization being delayed by approximately 1 week. By contrast, RNAi-induced down-regulation of the BvFT1-BvFT2 module led to a strong delay in bolting after vernalization by several weeks. The data demonstrate for the first time that an FLC homolog does not play a major role in the control of vernalization response in a dicot species outside the Brassicaceae. PMID:24782884

  4. Heterogeneity of Amygdala Response in Major Depressive Disorder: The Impact of Lifetime Sub-Threshold Mania

    PubMed Central

    Fournier, Jay C.; Keener, Matthew T.; Mullin, Benjamin C.; Hafeman, Danella M.; LaBarbara, Edmund J.; Stiffler, Richelle S.; Almeida, Jorge; Kronhaus, Dina M.; Frank, Ellen; Phillips, Mary L.

    2013-01-01

    Background Patients with major depressive disorder (MDD) present with highly heterogeneous symptom profiles. We aimed to examine whether individual differences in amygdala activity to emotionally-salient stimuli were related to heterogeneity in lifetime levels of depressive and sub-threshold manic symptoms among adults with MDD. Methods We compared age- and gender-matched adults with MDD (N=26) with healthy controls (HC, N=28). While undergoing fMRI, participants performed an implicit emotional faces task: they labeled a color flash superimposed upon initially neutral faces that dynamically morphed into one of four emotions (angry, fearful, sad, happy). Region of interest analyses examined group differences in amygdala activity. For conditions in which adults with MDD displayed abnormal amygdala activity versus HC, within-group analyses examined amygdala activity as a function of scores on a continuous measure of lifetime depression-related and mania-related pathology. Results Adults with MDD showed significantly greater right-sided amygdala activity to angry and happy conditions than HC (p<0.05, corrected). Multiple regression analyses revealed that greater right amygdala activity to the happy condition in adults with MDD was associated with higher levels of sub-threshold manic symptoms experienced across the lifespan (p=0.002). Conclusions Among depressed adults with MDD, lifetime features of sub-threshold mania were associated with abnormally elevated amygdala activity to emerging happy faces. These findings are a first step toward identifying biomarkers that reflect individual differences in neural mechanisms in MDD, and challenge conventional mood disorder diagnostic boundaries by suggesting that some adults with MDD are characterized by pathophysiologic processes that overlap with bipolar disorder. PMID:22571805

  5. Testing the estimated hypothetical response of the magnetosphere to a major space weather event

    NASA Astrophysics Data System (ADS)

    Bala, R.; Reiff, P. H.

    2014-12-01

    The high-speed CME, ejected on 23 July 2012, observed by STEREO A on the same day as the leading edge of the CME arrived at 1AU was unique in respect to the observed plasma and magnetic structure. STEREO A also observed large Solar Energetic Particle (SEP) flux increase prior to the CME onset. Because of its similarity in intensity to the great Carrington storm of 1859, it is referred to as "Carrington 2" event. Fortunately, the Earth was not on the path of the CME, otherwise it might have caused a major space weather event. We used the Rice Artificial Neural Network (ANN) algorithms with the solar wind and IMF parameters measured in situ by STEREO A as inputs to infer what the "geoeffectiveness" of that storm might have been. We are presently running our neural network models of Kp, Dst and AE on our realtime prediction site at http://mms.rice.edu/realtime/forecast.html. We modeled this event using our ANN-based Kp and Dst prediction algorithms to observe that, in fact, this would have been an extremely powerful geomagnetic storm. Our results show a prediction resulting in a Kp value of almost 9 and Dst of nearly -300 nT. However, when assumptions about Earth's dipole angle tilt (please see figure) and solar wind densities are made, predictions resulting in Kp of 9+ and Dst below -800 nT are found. Additionally, we also considered the effects of SEP flux, using STEREO A measurements, in our models. In doing so, the final Kp and Dst values rose further, with Kp reaching 10 and Dst dipping below -920 nT respectively.

  6. Linear sea-level response to abrupt ocean warming of major West Antarctic ice basin

    NASA Astrophysics Data System (ADS)

    Mengel, M.; Feldmann, J.; Levermann, A.

    2016-01-01

    Antarctica's contribution to global sea-level rise has recently been increasing. Whether its ice discharge will become unstable and decouple from anthropogenic forcing or increase linearly with the warming of the surrounding ocean is of fundamental importance. Under unabated greenhouse-gas emissions, ocean models indicate an abrupt intrusion of warm circumpolar deep water into the cavity below West Antarctica's Filchner-Ronne ice shelf within the next two centuries. The ice basin's retrograde bed slope would allow for an unstable ice-sheet retreat, but the buttressing of the large ice shelf and the narrow glacier troughs tend to inhibit such instability. It is unclear whether future ice loss will be dominated by ice instability or anthropogenic forcing. Here we show in regional and continental-scale ice-sheet simulations, which are capable of resolving unstable grounding-line retreat, that the sea-level response of the Filchner-Ronne ice basin is not dominated by ice instability and follows the strength of the forcing quasi-linearly. We find that the ice loss reduces after each pulse of projected warm water intrusion. The long-term sea-level contribution is approximately proportional to the total shelf-ice melt. Although the local instabilities might dominate the ice loss for weak oceanic warming, we find that the upper limit of ice discharge from the region is determined by the forcing and not by the marine ice-sheet instability.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection

    PubMed Central

    Gonzalez-Leal, Iris J.; Röger, Bianca; Schwarz, Angela; Schirmeister, Tanja; Reinheckel, Thomas; Lutz, Manfred B.; Moll, Heidrun

    2014-01-01

    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. PMID:25255101

  9. Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice

    PubMed Central

    1992-01-01

    Murine T cell responses to human class II major histocompatibility complex (MHC) molecules were shown to be a minimum of 20-70-fold lower than responses to allogeneic molecules. Transgenic mice expressing slightly below normal (75-95%) or very high (250-380%) cell surface levels of human CD4 were utilized to determine whether this was due to a species-specific interaction between murine CD4 and class II molecules. Human CD4 was shown to function in signal transduction events in murine T cells based on the ability of anti-human CD4 antibody to synergize with suboptimal doses of anti-murine CD3 antibody in stimulating T cell proliferation. In mice expressing lower levels of human CD4, T cell responses to human class II molecules were enhanced up to threefold, whereas allogeneic responses were unaltered. In mice expressing high levels of human CD4, responses to human class II molecules were enhanced at least 10-fold, whereas allogeneic responses were between one and three times the level of normal responses. The relatively greater enhancement of the response to human class II molecules in both lines argues for a preferential interaction between human CD4 and human class II molecules. In mice expressing lower levels of human CD4, responses to human class II molecules were blocked by antibodies to CD4 of either species, indicating participation by both molecules. In mice expressing high levels of human CD4, responses to both human and murine class II molecules were almost completely blocked with anti-human CD4 antibody, whereas anti-murine CD4 antibody had no effect. However, anti-murine CD4 continued to synergize with anti-CD3 in stimulating T cell proliferation in these mice. Thus, overexpression of human CD4 selectively impaired the ability of murine CD4 to assist in the process of antigen recognition. The ability of human CD4 to support a strong allogeneic response under these conditions indicates that this molecule can interact with murine class II molecules to a

  10. Transcriptomic insights into the molecular response of Saccharomyces cerevisiae to linoleic acid hydroperoxide.

    PubMed

    O'Doherty, P J; Lyons, V; Higgins, V J; Rogers, P J; Bailey, T D; Wu, M J

    2013-12-01

    Eukaryotic microorganisms are constantly challenged by reactive oxygen species derived endogenously or encountered in their environment. Such adversity is particularly applied to Saccharomyces cerevisiae under harsh industrial conditions. One of the major oxidants to challenge S. cerevisiae is linoleic acid hydroperoxide (LoaOOH). This study, which used genome-wide microarray analysis in conjunction with deletion mutant screening, uncovered the molecular pathways of S. cerevisiae that were altered by an arresting concentration of LoaOOH (75 μM). The oxidative stress response, iron homeostasis, detoxification through PDR transport and direct lipid β-oxidation were evident through the induction of the genes encoding for peroxiredoxins (GPX2, TSA2), the NADPH:oxidoreductase (OYE3), iron uptake (FIT2, ARN2, FET3), PDR transporters (PDR5, PDR15, SNQ2) and β-oxidation machinery (FAA2, POX1). Further, we discovered that Gpx3p, the dual redox sensor and peroxidase, is required for protection against LoaOOH, indicated by the sensitivity of gpx3Δ to a mild dose of LoaOOH (37.5 μM). Deletion of GPX3 conferred a greater sensitivity to LoaOOH than the loss of its signalling partner YAP1. Deletion of either of the iron homeostasis regulators AFT1 or AFT2 also resulted in sensitivity to LoaOOH. These novel findings for Gpx3p, Aft1p and Aft2p point to their distinct roles in response to the lipid peroxide. Finally, the expression of 89 previously uncharacterised genes was significantly altered against LoaOOH, which will contribute to their eventual annotation. PMID:24074273

  11. Major Barriers Responsible for Malnutrition in Hemodialysis Patients: Challenges to Optimal Nutrition

    PubMed Central

    Ekramzadeh, Maryam; Mazloom, Zohreh; Jafari, Peyman; Ayatollahi, Maryam; Sagheb, Mohammad Mahdi

    2014-01-01

    Background: Nutritional barriers may contribute to malnutrition in hemodialysis (HD) patients. Higher rates of morbidity and mortality rates have been reported in malnourished HD patients. These patients are faced with different challenges affecting their nutritional status. Objectives: The aim of this cross-sectional study was to identify most important barriers responsible for malnutrition in HD patients. Patients and Methods: We randomly selected 255 of 800 stable HD patients from three HD centers with an age range of 18-85 years, who had been on hemodialysis for at least three months without any acute illness. Each patient was interviewed to evaluate malnutrition [subjective global assessment (SGA), malnutrition inflammation score (MIS)], and potential medical, behavioral and socioeconomic barriers. Body composition of patients was checked through bioelectrical impedance analysis (BIA). Routine clinical markers of malnutrition such as serum albumin and total protein were measured using standard automated techniques. Binary logistic regression model was used to find the association between nutritional markers and potential barriers. Results: Patients with higher SGA had lower knowledge about general nutrition [odds ratio (OR), 1.3], potassium (OR, 1.89), difficulty chewing (OR, 1.16), and shopping (OR, 1.16). Those with greater MIS scores had poor appetite (OR, 1.3), depression (OR, 1.21), and difficulty with cooking (OR, 1.15). Lower BCM (body cell mass) was associated with poor appetite (OR, 0.92) and needed help for cooking (OR, 0.88). Patients with higher BFMI (body fat mass index) had insufficient general nutrition (OR, 1.15), and protein (OR, 1.27) knowledge, and needed help for shopping (OR, 1.14). Moreover, patients with higher SGA scores were those with older age and longer duration of HD. Conclusions: Three medical barriers (poor appetite, depression and difficulty chewing), one behavioral barrier (poor total nutrition, protein, and potassium knowledge

  12. HMGI-C rearrangements as the molecular basis for the majority of pulmonary chondroid hamartomas: a survey of 30 tumors.

    PubMed

    Kazmierczak, B; Rosigkeit, J; Wanschura, S; Meyer-Bolte, K; Van de Ven, W J; Kayser, K; Krieghoff, B; Kastendiek, H; Bartnitzke, S; Bullerdiek, J

    1996-02-01

    Pulmonary chondroid hamartomas (PCH) are benign tumors of the lung characterized by a more or less high degree of mesenchymal metaplasia. In our series we investigated 30 PCH by a combination of cytogenetic and molecular methods. 18 tumors (60%) had cytogenetically detectable aberrations involving either 12q14-15 or 6p21 with a clear predominance of chromosomal abnormalities involving 12q14-15 (15 tumors). As in subgroups of pleomorphic adenomas of the salivary glands, leiomyomas of the uterus, and lipomas with 12q14-15 abnormalities the HMGI-C gene is frequently rearranged we tested PCH with either 12q14-15 abnormalities or normal karyotype by FISH and 3' RACE experiments for rearrangements of HMGI-C. Rearrangements were found in all cases with chromosomal 12q14-15 abnormalities and further six cases with an apparently normal karyotype. By the combination of cytogenetics with molecular techniques the percentage of cases with intragenic rearrangements of HMGI-C or rearrangements of its immediate surrounding was thus increased to 70% (21/30 cases). Considering all types of aberrations within this series 80% (24/30) of all PCH were aberrant. This is the first report on a combined molecular and cytogenetic analysis of a large series of pulmonary chondroid hamartomas indicating that rearrangements of HMGI-C, a member of the high mobility group protein gene family, are the leading molecular events in the genesis of PCH.

  13. Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

    PubMed Central

    Hammer, Christian; Begemann, Martin; McLaren, Paul J.; Bartha, István; Michel, Angelika; Klose, Beate; Schmitt, Corinna; Waterboer, Tim; Pawlita, Michael; Schulz, Thomas F.; Ehrenreich, Hannelore; Fellay, Jacques

    2015-01-01

    The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans. PMID:26456283

  14. Growth hormone response to catecholamine depletion in unmedicated, remitted subjects with major depressive disorder and healthy controls.

    PubMed

    Homan, Philipp; Drevets, Wayne C; Hasler, Gregor

    2013-10-01

    We investigated whether the human growth hormone (HGH) response to catecholamine depletion differs between fully remitted patients with major depressive disorder and healthy control subjects. Fourteen unmedicated subjects with remitted major depressive disorder (RMDD) and 11 healthy control subjects underwent catecholamine depletion with oral α-methylparatyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the serum level of HGH. The diagnosis × drug interaction for HGH serum concentration was significant (F₁,₂₃ = 7.66, P < 0.02). This interaction was attributable to the HGH level increasing after AMPT administration in the RMDD subjects but not in the healthy subjects. In the RMDD sample, the AMPT-induced increase in HGH concentration correlated inversely with AMPT-induced anxiety symptoms as assessed using the Beck Anxiety Inventory (r = -0.63, P < 0.02). There was a trend toward an inverse correlation of the AMPT-induced HGH concentration changes with AMPT-induced depressive symptoms as measured by the BDI (r = -0.53, P = 0.05). Following catecholamine depletion, the RMDD subjects were differentiated from control subjects by their HGH responses. This finding, together with the negative correlation between HGH response and AMPT-induced anxiety symptoms in RMDD subjects, suggests that AMPT administration results in a deeper nadir in central catecholaminergic transmission, as reflected by a greater disinhibition of HGH secretion, in RMDD subjects versus control subjects.

  15. Major latex protein-like protein 43 (MLP43) functions as a positive regulator during abscisic acid responses and confers drought tolerance in Arabidopsis thaliana

    PubMed Central

    Wang, Yanping; Yang, Li; Chen, Xi; Ye, Tiantian; Zhong, Bao; Liu, Ruijie; Wu, Yan; Chan, Zhulong

    2016-01-01

    Drought stress is one of the disadvantageous environmental conditions for plant growth and reproduction. Given the importance of abscisic acid (ABA) to plant growth and abiotic stress responses, identification of novel components involved in ABA signalling transduction is critical. In this study, we screened numerous Arabidopsis thaliana mutants by seed germination assay and identified a mutant mlp43 (major latex protein-like 43) with decreased ABA sensitivity in seed germination. The mlp43 mutant was sensitive to drought stress while the MLP43-overexpressed transgenic plants were drought tolerant. The tissue-specific expression pattern analysis showed that MLP43 was predominantly expressed in cotyledons, primary roots and apical meristems, and a subcellular localization study indicated that MLP43 was localized in the nucleus and cytoplasm. Physiological and biochemical analyses indicated that MLP43 functioned as a positive regulator in ABA- and drought-stress responses in Arabidopsis through regulating water loss efficiency, electrolyte leakage, ROS levels, and as well as ABA-responsive gene expression. Moreover, metabolite profiling analysis indicated that MLP43 could modulate the production of primary metabolites under drought stress conditions. Reconstitution of ABA signalling components in Arabidopsis protoplasts indicated that MLP43 was involved in ABA signalling transduction and acted upstream of SnRK2s by directly interacting with SnRK2.6 and ABF1 in a yeast two-hybrid assay. Moreover, ABA and drought stress down-regulated MLP43 expression as a negative feedback loop regulation to the performance of MLP43 in ABA and drought stress responses. Therefore, this study provided new insights for interpretation of physiological and molecular mechanisms of Arabidopsis MLP43 mediating ABA signalling transduction and drought stress responses. PMID:26512059

  16. Major latex protein-like protein 43 (MLP43) functions as a positive regulator during abscisic acid responses and confers drought tolerance in Arabidopsis thaliana.

    PubMed

    Wang, Yanping; Yang, Li; Chen, Xi; Ye, Tiantian; Zhong, Bao; Liu, Ruijie; Wu, Yan; Chan, Zhulong

    2016-01-01

    Drought stress is one of the disadvantageous environmental conditions for plant growth and reproduction. Given the importance of abscisic acid (ABA) to plant growth and abiotic stress responses, identification of novel components involved in ABA signalling transduction is critical. In this study, we screened numerous Arabidopsis thaliana mutants by seed germination assay and identified a mutant mlp43 (major latex protein-like 43) with decreased ABA sensitivity in seed germination. The mlp43 mutant was sensitive to drought stress while the MLP43-overexpressed transgenic plants were drought tolerant. The tissue-specific expression pattern analysis showed that MLP43 was predominantly expressed in cotyledons, primary roots and apical meristems, and a subcellular localization study indicated that MLP43 was localized in the nucleus and cytoplasm. Physiological and biochemical analyses indicated that MLP43 functioned as a positive regulator in ABA- and drought-stress responses in Arabidopsis through regulating water loss efficiency, electrolyte leakage, ROS levels, and as well as ABA-responsive gene expression. Moreover, metabolite profiling analysis indicated that MLP43 could modulate the production of primary metabolites under drought stress conditions. Reconstitution of ABA signalling components in Arabidopsis protoplasts indicated that MLP43 was involved in ABA signalling transduction and acted upstream of SnRK2s by directly interacting with SnRK2.6 and ABF1 in a yeast two-hybrid assay. Moreover, ABA and drought stress down-regulated MLP43 expression as a negative feedback loop regulation to the performance of MLP43 in ABA and drought stress responses. Therefore, this study provided new insights for interpretation of physiological and molecular mechanisms of Arabidopsis MLP43 mediating ABA signalling transduction and drought stress responses.

  17. Genome-wide association studies identifies seven major regions responsible for iron deficiency chlorosis in soybean (Glycine max).

    PubMed

    Mamidi, Sujan; Lee, Rian K; Goos, Jay R; McClean, Phillip E

    2014-01-01

    Iron deficiency chlorosis (IDC) is a yield limiting problem in soybean (Glycine max (L.) Merr) production regions with calcareous soils. Genome-wide association study (GWAS) was performed using a high density SNP map to discover significant markers, QTL and candidate genes associated with IDC trait variation. A stepwise regression model included eight markers after considering LD between markers, and identified seven major effect QTL on seven chromosomes. Twelve candidate genes known to be associated with iron metabolism mapped near these QTL supporting the polygenic nature of IDC. A non-synonymous substitution with the highest significance in a major QTL region suggests soybean orthologs of FRE1 on Gm03 is a major gene responsible for trait variation. NAS3, a gene that encodes the enzyme nicotianamine synthase which synthesizes the iron chelator nicotianamine also maps to the same QTL region. Disease resistant genes also map to the major QTL, supporting the hypothesis that pathogens compete with the plant for Fe and increase iron deficiency. The markers and the allelic combinations identified here can be further used for marker assisted selection.

  18. Genome-Wide Association Studies Identifies Seven Major Regions Responsible for Iron Deficiency Chlorosis in Soybean (Glycine max)

    PubMed Central

    Mamidi, Sujan; Lee, Rian K.; Goos, Jay R.; McClean, Phillip E.

    2014-01-01

    Iron deficiency chlorosis (IDC) is a yield limiting problem in soybean (Glycine max (L.) Merr) production regions with calcareous soils. Genome-wide association study (GWAS) was performed using a high density SNP map to discover significant markers, QTL and candidate genes associated with IDC trait variation. A stepwise regression model included eight markers after considering LD between markers, and identified seven major effect QTL on seven chromosomes. Twelve candidate genes known to be associated with iron metabolism mapped near these QTL supporting the polygenic nature of IDC. A non-synonymous substitution with the highest significance in a major QTL region suggests soybean orthologs of FRE1 on Gm03 is a major gene responsible for trait variation. NAS3, a gene that encodes the enzyme nicotianamine synthase which synthesizes the iron chelator nicotianamine also maps to the same QTL region. Disease resistant genes also map to the major QTL, supporting the hypothesis that pathogens compete with the plant for Fe and increase iron deficiency. The markers and the allelic combinations identified here can be further used for marker assisted selection. PMID:25225893

  19. Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

    PubMed Central

    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

  20. Similarities in acute phase protein response during hibernation in black bears and major depression in humans: A response to underlying metabolic depression?

    USGS Publications Warehouse

    Tsiouris, J.A.; Chauhan, V.P.S.; Sheikh, A.M.; Chauhan, A.; Malik, M.; Vaughan, M.R.

    2004-01-01

    This study investigated the effects of hibernation with mild hypothermia and the stress of captivity on levels of six acute-phase proteins (APPs) in serial samples of serum from 11 wild and 6 captive black bears (Ursus americanus Pallas, 1780) during active and hibernating states. We hypothesize that during hibernation with mild hypothermia, bears would show an APP response similar to that observed in major depression. Enzyme-linked immunoabsorbent assay was used to measure alpha2-macroglobulin and C-reactive protein, and a nephelometer to measure alpha1-antitrypsin, haptoglobin, ceruloplasmin, and transferrin. Levels of all other proteins except ceruloplasmin were significantly elevated during hibernation in both wild and captive bears at the p < 0.05 to p < 0.001 level. Alpha 2-macroglobulin and C-reactive-protein levels were increased in captive versus wild bears in both active and hibernating states at the p < 0.01 to p < 0.0001 level. During hibernation with mild hypothermia, black bears do not show immunosuppression, but show an increased APP response similar to that in patients with major depression. This APP response is explained as an adaptive response to the underlying metabolic depression in both conditions. Metabolic depression in hibernating bears is suggested as a natural model for research to explain the neurobiology of depression.

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

    PubMed

    Williams, Casey B; McMahon, Caitlin; Ali, Siraj M; Abramovitz, Mark; Williams, Kirstin A; Klein, Jessica; McKean, Heidi; Yelensky, Roman; George, Thomas J; Elvin, Julia A; Soman, Salil; Lipson, Doron; Chmielecki, Juliann; Morosini, Deborah; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Leyland-Jones, Brian

    2015-01-01

    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. PMID:26664139

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

    PubMed Central

    Williams, Casey B; McMahon, Caitlin; Ali, Siraj M; Abramovitz, Mark; Williams, Kirstin A; Klein, Jessica; McKean, Heidi; Yelensky, Roman; George, Thomas J; Elvin, Julia A; Soman, Salil; Lipson, Doron; Chmielecki, Juliann; Morosini, Deborah; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Leyland-Jones, Brian

    2015-01-01

    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. PMID:26664139

  3. Molecular monitoring 101: helping your patients with chronic myeloid leukemia to understand the meaning of molecular response.

    PubMed

    Jabbour, Elias J; Quintás-Cardama, Alfonso

    2012-08-01

    For patients with chronic myeloid leukemia (CML), measurement of molecular response (i.e. the level of BCR-ABL1 transcripts) is firmly established as a key element of disease monitoring. Assessment of BCR-ABL1 levels may help to identify early signs of resistance to treatment and enable a timely switch to alternative therapies. Hence, regular and accurate monitoring of BCR-ABL1 transcripts helps to maximize the chance of successful outcomes in CML. Because the incidence of CML is relatively low, many community oncologists encounter only a limited number of cases; measuring and interpreting BCR-ABL1 measurements in a clinically relevant fashion may be challenging. The team at our institution often encounters questions regarding real-time quantitative polymerase chain reaction assessments of BCR-ABL1 levels, International Scale standardization, the implications of achieving or losing molecular responses and mutation monitoring. The aim of this article is to provide practical advice for effective long-term monitoring of patients with CML by addressing frequently asked questions and common case scenarios using guideline- and evidence-based approaches. PMID:22273251

  4. Different Morphologies of Leishmania major Amastigotes with No Molecular Diversity in a Neglected Endemic Area of Zoonotic Cutaneous Leishmaniasis in Iran

    PubMed Central

    Spotin, Adel; Rouhani, Soheila; Ghaemmaghami, Parnazsadat; Haghighi, Ali; Zolfaghari, Mohammad Reza; Amirkhani, Aref; Farahmand, Mahin; Bordbar, Ali; Parvizi, Parviz

    2015-01-01

    Background: Molecular diversity of Leishmania major and its morphological changes have become a controversial issue among researchers. Some aspects of polymorphic shapes of amastigotes in clinical manifestations along with molecular variation were evaluated among suspected patients of some exceptional zoonotic cutaneous leishmaniasis locations in Northern Khuzestan, Southwestern Iran. Methods: Suspected patients (n = 165) were sampled in zoonotic cutaneous leishmaniasis foci over two consecutive years during 2012-2014. Prepared smears were stained, scaled and measured by ocular micrometer. DNA was extracted from smears; ITS-rDNA and Cytochrome b (Cyt b) markers were amplified, and PCR products were digested by BsuR1 restriction enzyme. Then the RFLP and sequencing were employed. Results: Only L. major was identified in patients containing regular amastigotes' shapes (oval or round) with a size of 2-4 µm in each of classical wet, dry, mixed lesions. Meanwhile, irregular shapes (spindle, pear, or cigarette) were observed separately in non-classical wet lesions with more than 4 µm. Interestingly, a few amastigotes with an external flagellum were observed in some lesions. All sequenced ITS-rDNA and Cyt b genes of L. major did not show any molecular variation (χ 2 P > 0.05), including only one common haplotype (GenBank access no. EF413075). Conclusion: Findings proved that unlike other endemic foci, there is not a meaningful correlation between phenotypic and genotypic features of L. major isolates. This study is considered as the first comprehensive report to incriminate morphometric shapes of L. major amastigotes, which enhances our knowledge concerning their relevance with various clinical appearances and genotypic traits. PMID:26081070

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

    PubMed

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

    PubMed

    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

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

    EPA Science Inventory

    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. Condensed-to-atoms hardness kernel from the response of molecular fragment approach

    NASA Astrophysics Data System (ADS)

    Miranda-Quintana, Ramón Alain

    2016-08-01

    Condensed reactivity descriptors obtained from the response of molecular fragment (RMF) approach are analyzed within the variational formulation of conceptual density functional theory. It is shown that this approach can serve as the basis of a coherent formulation of the hardness kernel.

  9. Inherent insulin sensitivity is a major determinant of multimeric adiponectin responsiveness to short-term weight loss in extreme obesity

    PubMed Central

    Mai, Stefania; Walker, Gillian E.; Brunani, Amelia; Guzzaloni, Gabriele; Grossi, Glenda; Oldani, Alberto; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

    2014-01-01

    High molecular weight (HMW-A) adiponectin levels mirror alterations in glucose homeostasis better than medium (MMW-A) and low molecular weight (LMW-A) components. In 25 patients with wide-range extreme obesity (BMI 40-77 kg/m2), we aimed to explore if improvements of multimeric adiponectin following 4-wk weight loss reflect baseline OGTT-derived insulin sensitivity (ISIOGTT) and disposition index (DIOGTT). Compared to 40 lean controls, adiponectin oligomers were lower in extreme obesity (p < 0.001) and, within this group, HMW-A levels were higher in insulin-sensitive (p < 0.05) than -resistant patients. In obese patients, short-term weight loss did not change total adiponectin levels and insulin resistance, while the distribution pattern of adiponectin oligomers changed due to significant increment of HMW-A (p < 0.01) and reduction of MMW-A (p < 0.05). By multivariate analysis, final HMW-A levels were significantly related to baseline ISIOGTT and final body weight (adjusted R2 = 0.41). Our data suggest that HMW adiponectin may reflect baseline insulin sensitivity appropriately in the context of extreme obesity. Especially, we documented that HMW-A is promptly responsive to short-term weight loss prior to changes in insulin resistance, by a magnitude that is proportioned to whole body insulin sensitivity. This may suggest an insulin sensitivity-dependent control operated by HMW-A on metabolic dynamics of patients with extreme obesity. PMID:25056918

  10. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study.

    PubMed

    Miller, Jeffrey Morris; Schneck, Noam; Siegle, Greg J; Chen, Yakuan; Ogden, R Todd; Kikuchi, Toshiaki; Oquendo, Maria A; Mann, J John; Parsey, Ramin V

    2013-12-30

    Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial.

  11. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study

    PubMed Central

    Miller, Jeffrey Morris; Schneck, Noam; Siegle, Greg J.; Chen, Yakuan; Ogden, R. Todd; Kikuchi, Toshiaki; Oquendo, Maria A.; Mann, J. John; Parsey, Ramin V.

    2013-01-01

    Clinically useful predictors of treatment outcome in major depressive disorder (MDD) remain elusive. We examined associations between functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal during active negative word processing and subsequent selective serotonin reuptake inhibitor (SSRI) treatment outcome in MDD. Unmedicated MDD subjects (n=17) performed an emotional word processing fMRI task, and then received eight weeks of standardized antidepressant treatment with escitalopram. Lower pre-treatment BOLD responses to negative words in midbrain, dorsolateral prefrontal cortex, paracingulate, anterior cingulate, thalamus and caudate nuclei correlated significantly with greater improvement following escitalopram treatment. Activation of these regions in response to negative words correlated significantly with reaction time for rating word relevance. Maximally predictive clusters of voxels identified using a cross-validation approach predicted 48% of the variance in response to treatment. This study provides preliminary evidence that SSRIs may be most beneficial in patients who are less able to engage cognitive control networks while processing negative stimuli. Differences between these findings and previous fMRI studies of SSRI treatment outcome may relate to differences in task design. Regional BOLD responses to negative words predictive of SSRI outcome in this study were both overlapping and distinct from those predictive of outcome with cognitive behavioral therapy (CBT) in previous studies using the same task. Future studies may examine prediction of differential outcome across treatments in the context of a randomized controlled trial. PMID:24446548

  12. Bacteroides fragilis in biopsies of patients with major abscesses and diabetic foot infections: direct molecular versus culture-based detection.

    PubMed

    Stappers, Mark H T; Hagen, Ferry; Reimnitz, Peter; Mouton, Johan W; Meis, Jacques F; Gyssens, Inge C

    2016-06-01

    Direct determination by pathogen-specific real-time PCR assay for Bacteroides fragilis was compared to culture in major abscess and diabetic foot infection biopsy samples. Real-time PCR resulted in an increased detection rate of 12% for B. fragilis and could improve the detection of B. fragilis in clinical samples. PMID:27112830

  13. Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

    PubMed Central

    Hoyo-Becerra, Carolina; Erim, Yesim; Kis, Bernhard; Wang, Bo; Scherbaum, Norbert; Gerken, Guido

    2012-01-01

    Background Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood. Methods 50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed. Results IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients. Conclusions Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders. PMID:22701688

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Molecular targeting of CSN5 in human hepatocellular carcinoma: a mechanism of therapeutic response

    PubMed Central

    Lee, Y-H; Judge, AD; Seo, D; Kitade, M; Gómez-Quiroz, LE; Ishikawa, T; Andersen, JB; Kim, B-K; Marquardt, JU; Raggi, C; Avital, I; Conner, EA; MacLachlan, I; Factor, VM; Thorgeirsson, SS

    2011-01-01

    Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared to dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. Our results show that CSN5 knockdown by small interfering (si) RNA caused a strong induction of apoptosis and inhibition of cell cycle progression in HCC cells in vitro. The downregulation of CSN5 was sufficient to interfere with CSN function as evidenced by the accumulation of neddylated Cullin1 and changes in the protein levels of CSN controlled substrates SKP2, p53, p27 and NF-kB, albeit to a different degree depending on the HCC cell line, which could account for the CSN5 knockdown phenotype. The transcriptomic analysis of CSN5 knockdown signature showed that the anti-proliferative effect was driven by a common subset of molecular alterations including downregulation of CDK6 and ITGB1, which were functionally interconnected with key oncogenic regulators MYC and TGFβ1 involved in the control of proliferation, apoptotic cell death and HCC progression. Consistent with microarray analysis, western blotting revealed that CSN5 depletion increased phosphorylation of Smad 2/3, key mediators of TGFβ1 signaling, decreased the protein levels of ITGB1, CDK6, and cyclin D1 and caused reduced expression of anti-apoptotic Bcl-2 while elevating the levels of pro-apoptotic Bak. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid-particles (SNALP) significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 plays a pivotal role in HCC pathogenesis and maybe an attractive molecular

  16. Phe362Tyr in AChE: A Major Factor Responsible for Azamethiphos Resistance in Lepeophtheirus salmonis in Norway

    PubMed Central

    Kaur, Kiranpreet; Jansen, Peder Andreas; Aspehaug, Vidar Teis; Horsberg, Tor Einar

    2016-01-01

    Organophosphates (OP) are one of the major treatments used against the salmon louse (Lepeophtherius salmonis) in Norwegian salmonid aquaculture. The use of OP since the late 1970s has resulted in widespread resistant parasites. Recently, we reported a single mutation (Phe362Tyr) in acetylcholinesterase (AChE) as the major mechanism behind resistance in salmon louse towards OP. The present study was carried out to validate this mechanism at the field level. A total of 6658 salmon louse samples were enrolled from 56 different fish farms across the Norwegian coast, from Vest Agder in the south to Finnmark in the north. All the samples were genotyped using a TaqMan probe assay for the Phe362Tyr mutation. A strong association was observed between areas with frequent use of the OP (azamethiphos) and the Phe362Tyr mutation. This was confirmed at 15 sites where results from independently conducted bioassays and genotyping of parasites correlated well. Furthermore, genotyping of surviving and moribund parasites from six bioassay experiments demonstrated a highly significant negative correlation between the frequency of resistance alleles and the probability of dying when exposed to azamethiphos in a bioassay. Based on these observations, we could strongly conclude that the Phe362Tyr mutation is a major factor responsible for OP resistance in salmon louse on Norwegian fish farms. PMID:26882536

  17. Phe362Tyr in AChE: A Major Factor Responsible for Azamethiphos Resistance in Lepeophtheirus salmonis in Norway.

    PubMed

    Kaur, Kiranpreet; Jansen, Peder Andreas; Aspehaug, Vidar Teis; Horsberg, Tor Einar

    2016-01-01

    Organophosphates (OP) are one of the major treatments used against the salmon louse (Lepeophtherius salmonis) in Norwegian salmonid aquaculture. The use of OP since the late 1970s has resulted in widespread resistant parasites. Recently, we reported a single mutation (Phe362Tyr) in acetylcholinesterase (AChE) as the major mechanism behind resistance in salmon louse towards OP. The present study was carried out to validate this mechanism at the field level. A total of 6658 salmon louse samples were enrolled from 56 different fish farms across the Norwegian coast, from Vest Agder in the south to Finnmark in the north. All the samples were genotyped using a TaqMan probe assay for the Phe362Tyr mutation. A strong association was observed between areas with frequent use of the OP (azamethiphos) and the Phe362Tyr mutation. This was confirmed at 15 sites where results from independently conducted bioassays and genotyping of parasites correlated well. Furthermore, genotyping of surviving and moribund parasites from six bioassay experiments demonstrated a highly significant negative correlation between the frequency of resistance alleles and the probability of dying when exposed to azamethiphos in a bioassay. Based on these observations, we could strongly conclude that the Phe362Tyr mutation is a major factor responsible for OP resistance in salmon louse on Norwegian fish farms. PMID:26882536

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

    PubMed

    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

    2012-02-01

    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.

  19. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response. PMID:27622047

  20. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response.

  1. Adaptive responses and disruptive effects: how major wildfire influences kinship-based social interactions in a forest marsupial.

    PubMed

    Banks, Sam C; Blyton, Michaela D J; Blair, David; McBurney, Lachlan; Lindenmayer, David B

    2012-02-01

    Environmental disturbance is predicted to play a key role in the evolution of animal social behaviour. This is because disturbance affects key factors underlying social systems, such as demography, resource availability and genetic structure. However, because natural disturbances are unpredictable there is little information on their effects on social behaviour in wild populations. Here, we investigated how a major wildfire affected cooperation (sharing of hollow trees) by a hollow-dependent marsupial. We based two alternative social predictions on the impacts of fire on population density, genetic structure and resources. We predicted an adaptive social response from previous work showing that kin selection in den-sharing develops as competition for den resources increases. Thus, kin selection should occur in burnt areas because the fire caused loss of the majority of hollow-bearing trees, but no detectable mortality. Alternatively, fire may have a disruptive social effect, whereby postfire home range-shifts 'neutralize' fine-scale genetic structure, thereby removing opportunities for kin selection between neighbours. Both predictions occurred: the disruptive social effect in burnt habitat and the adaptive social response in adjacent unburnt habitat. The latter followed a massive demographic influx to unburnt 'refuge' habitat that increased competition for dens, leading to a density-related kin selection response. Our results show remarkable short-term plasticity of animal social behaviour and demonstrate how the social effects of disturbance extend into undisturbed habitat owing to landscape-scale demographic shifts. We predicted long-term changes in kinship-based cooperative behaviour resulting from the genetic and resource impacts of forecast changes to fire regimes in these forests.

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

    PubMed Central

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

    2016-01-01

    Objective 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. Setting Early prehospital phase of a major incident. Design 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. Results 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. Conclusions 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. Trial registration number CRD42013004473. PMID:26861938

  3. Dominance Is the Major Genetic Basis of Heterosis in Rice as Revealed by Qtl Analysis Using Molecular Markers

    PubMed Central

    Xiao, J.; Li, J.; Yuan, L.; Tanksley, S. D.

    1995-01-01

    A set of 194 F(7) lines derived from a subspecific rice cross showing strong F(1) heterosis was backcrossed to the two parents. The materials (388 BC(1)F(7) lines, 194 F(8) lines, two parents, F(1)) were phenotyped for 12 quantitative traits. A total of 37 significant QTLs (LOD >/= 2.0) was detected through 141 RFLP markers in the BC(1)F(7) populations. Twenty-seven (73%) quantitative trait loci (QTLs) were detected in only one of the BC(1)F(7) populations. In 82% of these cases, the heterozygotes were superior to the respective homozygotes. The remaining 10 (27%) QTLs were detected in both BC(1)F(7) populations, and the heterozygote had a phenotype falling between those of the two homozygotes and in no instances were the heterozygotes found to be superior to both homozygotes. These results suggest that dominance complementation is the major genetic basis of heterosis in rice. This conclusion was strengthened by the finding that there was no correlation between most traits and overall genome heterozygosity and that there were some recombinant inbred lines in the F(8) population having phenotypic values superior to the F(1) for all of the traits evaluated--a result not expected if overdominance was a major contributor to heterosis. Digenic epistasis was not evident. PMID:7498751

  4. Molecular response properties from a Hermitian eigenvalue equation for a time-periodic Hamiltonian

    NASA Astrophysics Data System (ADS)

    Pawłowski, Filip; Olsen, Jeppe; Jørgensen, Poul

    2015-03-01

    The time-dependent Schrödinger equation for a time-periodic perturbation is recasted into a Hermitian eigenvalue equation, where the quasi-energy is an eigenvalue and the time-periodic regular wave function an eigenstate. From this Hermitian eigenvalue equation, a rigorous and transparent formulation of response function theory is developed where (i) molecular properties are defined as derivatives of the quasi-energy with respect to perturbation strengths, (ii) the quasi-energy can be determined from the time-periodic regular wave function using a variational principle or via projection, and (iii) the parametrization of the unperturbed state can differ from the parametrization of the time evolution of this state. This development brings the definition of molecular properties and their determination on par for static and time-periodic perturbations and removes inaccuracies and inconsistencies of previous response function theory formulations. The development where the parametrization of the unperturbed state and its time evolution may differ also extends the range of the wave function models for which response functions can be determined. The simplicity and universality of the presented formulation is illustrated by applying it to the configuration interaction (CI) and the coupled cluster (CC) wave function models and by introducing a new model—the coupled cluster configuration interaction (CC-CI) model—where a coupled cluster exponential parametrization is used for the unperturbed state and a linear parametrization for its time evolution. For static perturbations, the CC-CI response functions are shown to be the analytical analogues of the static molecular properties obtained from finite field equation-of-motion coupled cluster (EOMCC) energy calculations. The structural similarities and differences between the CI, CC, and CC-CI response functions are also discussed with emphasis on linear versus non-linear parametrizations and the size-extensivity of the

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

    PubMed

    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

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

    PubMed

    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

  7. Decipher the Molecular Response of Plant Single Cell Types to Environmental Stresses

    DOE PAGESBeta

    Nourbakhsh-Rey, Mehrnoush; Libault, Marc

    2016-01-01

    The analysis of the molecular response of entire plants or organs to environmental stresses suffers from the cellular complexity of the samples used. Specifically, this cellular complexity masks cell-specific responses to environmental stresses and logically leads to the dilution of the molecular changes occurring in each cell type composing the tissue/organ/plant in response to the stress. Therefore, to generate a more accurate picture of these responses, scientists are focusing on plant single cell type approaches. Several cell types are now considered as models such as the pollen, the trichomes, the cotton fiber, various root cell types including the root hairmore » cell, and the guard cell of stomata. Among them, several have been used to characterize plant response to abiotic and biotic stresses. Lastly, in this review, we are describing the various -omic studies performed on these different plant single cell type models to better understand plant cell response to biotic and abiotic stresses.« less

  8. Molecular and immunological characterization of the first allergenic lipocalin in hamster: the major allergen from Siberian hamster (Phodopus sungorus).

    PubMed

    Torres, José Alberto; de Las Heras, Manuel; Maroto, Aroa Sanz; Vivanco, Fernando; Sastre, Joaquín; Pastor-Vargas, Carlos

    2014-08-22

    The most frequent pet allergy is to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is more prevalent. The list of new pets includes hamsters, and one of the most popular hamsters is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve the specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine, and salivary glands of four hamster species (European, golden, Siberian, and Roborovski). IgE-binding proteins were detected by immunoblotting and identified by mass spectrometry. The recombinant protein was produced in Escherichia coli and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting, and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obtained from Siberian hamster hair, urine, and salivary glands. All proteins corresponded to the same protein, which was identified as a lipocalin. This lipocalin had no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to Siberian hamster protein extracts. Also, the recombinant allergen was capable of producing biological activation in vivo. The major Siberian hamster allergen was cloned, and allergenic properties were characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.

  9. Molecular and immunological characterization and IgE epitope mapping of Pen n 18, a major allergen of Penicillium notatum.

    PubMed Central

    Yu, Chia-Jung; Chen, Yen-Ming; Su, Song-Nan; Forouhar, Farhad; Lee, Shu-Hua; Chow, Lu-Ping

    2002-01-01

    The mould genus, Penicillium, is a significant source of environmental aero-allergens. A major allergen from Penicillium notatum, Pen n 18, was identified by two-dimensional immunoblotting using monoclonal antibody G11A10, raised against the vacuolar serine protease of Penicillium citrinum, followed by matrix-assisted laser-desorption ionization-time-of-flight MS analysis of the peptide digest. Pen n 18 was then cloned and the amino acid sequence deduced from the cDNA sequence. The cDNA encoded a 494 amino acid protein, considerably larger than mature Pen n 18, the differences being due to the N- and C-terminal prosequences. The deduced amino acid sequence showed extensive similarity with those of vacuolar serine proteases from various fungi. The Pen n 18 coding sequence was expressed in Escherichia coli as a His-tagged fusion protein and purified by Ni(2+)-chelate affinity chromatography. On immunoblots, the purified recombinant protein specifically bound IgE from mould-allergic patients, and cross-inhibition assays demonstrated the presence of common IgE-binding epitopes on Pen n 18 and a major allergen of P. citrinum, Pen c 18. When mapping of the allergenic epitopes was performed, at least nine different linear IgE-binding epitopes, located throughout the Pen n 18 protein, were identified. Of these, peptide C12, located in the N-terminal region of the molecule, was recognized by serum from 75% of the patients tested and therefore appears to be an immunodominant IgE-binding epitope. PMID:11964171

  10. Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

    PubMed Central

    Xu, Hongyan; Lam, Siew Hong; Shen, Yuan; Gong, Zhiyuan

    2013-01-01

    Inorganic arsenic is a worldwide metalloid pollutant in environment. Although extensive studies on arsenic-induced toxicity have been conducted using in vivo and in vitro models, the exact molecular mechanism of arsenate toxicity remains elusive. Here, the RNA-SAGE (serial analysis of gene expression) sequencing technology was used to analyse hepatic response to arsenic exposure at the transcriptome level. Based on more than 12 million SAGE tags mapped to zebrafish genes, 1,444 differentially expressed genes (750 up-regulated and 694 down-regulated) were identified from a relatively abundant transcripts (>10 TPM [transcripts per million]) based on minimal two-fold change. By gene ontology analyses, these differentially expressed genes were significantly enriched in several major biological processes including oxidation reduction, translation, iron ion transport, cell redox, homeostasis, etc. Accordingly, the main pathways disturbed include metabolic pathways, proteasome, oxidative phosphorylation, cancer, etc. Ingenity Pathway Analysis further revealed a network with four important upstream factors or hub genes, including Jun, Kras, APoE and Nr2f2. The network indicated apparent molecular events involved in oxidative stress, carcinogenesis, and metabolism. In order to identify potential biomarker genes for arsenic exposure, 27 out of 29 up-regulated transcripts were validated by RT-qPCR analysis in pooled RNA samples. Among these, 14 transcripts were further confirmed for up-regulation by a lower dosage of arsenic in majority of individual zebrafish. Finally, at least four of these genes, frh3 (ferrintin H3), mgst1 (microsomal glutathione S-transferase-like), cmbl (carboxymethylenebutenolidase homolog) and slc40a1 (solute carrier family 40 [iron-regulated transporter], member 1) could be confirmed in individual medaka fish similarly treated by arsenic; thus, these four genes might be robust arsenic biomarkers across species. Thus, our work represents the first

  11. Tea consumption and the risk of five major cancers: a dose–response meta-analysis of prospective studies

    PubMed Central

    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. Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation[S

    PubMed Central

    Jarrar, Yazun Bashir; Cha, Eun-Young; Seo, Kyung-Ah; Ghim, Jong-Lyul; Kim, Hyo-Ji; Kim, Dong-Hyun; Lee, Su-Jun; Shin, Jae-Gook

    2014-01-01

    The compound 20-HETE is involved in numerous physiological functions, including blood pressure and platelet aggregation. Glucuronidation of 20-HETE by UDP-glucuronosyltransferases (UGTs) is thought to be a primary pathway of 20-HETE elimination in humans. The present study identified major UGT enzymes responsible for 20-HETE glucuronidation and investigated their genetic influence on the glucuronidation reaction using human livers (n = 44). Twelve recombinant UGTs were screened to identify major contributors to 20-HETE glucuronidation. Based on these results, UGT2B7, UGT1A9, and UGT1A3 exhibited as major contributors to 20-HETE glucuronidation. The Km values of 20-HETE glucuronidation by UGT1A3, UGT1A9, and UGT2B7 were 78.4, 22.2, and 14.8 μM, respectively, while Vmax values were 1.33, 1.78, and 1.62 nmol/min/mg protein, respectively. Protein expression levels and genetic variants of UGT1A3, UGT1A9, and UGT2B7 were analyzed in human livers using Western blotting and genotyping, respectively. Glucuronidation of 20-HETE was significantly correlated with the protein levels of UGT2B7 (r2 = 0.33, P < 0.001) and UGT1A9 (r2 = 0.31, P < 0.001), but not UGT1A3 (r2 = 0.02, P > 0.05). A correlation between genotype and 20-HETE glucuronidation revealed that UGT2B7 802C>T, UGT1A9 −118T9>T10, and UGT1A9 1399T>C significantly altered 20-HETE glucuronide formation (P < 0.05–0.001). Increased levels of 20-HETE comprise a risk factor for cardiovascular diseases, and the present data may increase our understanding of 20-HETE metabolism and cardiovascular complications. PMID:25249502

  13. Protective vaccination with promastigote surface antigen 2 from Leishmania major is mediated by a TH1 type of immune response.

    PubMed

    Handman, E; Symons, F M; Baldwin, T M; Curtis, J M; Scheerlinck, J P

    1995-11-01

    Leishmania major promastigote surface antigen-2 complex (PSA-2) comprises a family of three similar but distinct polypeptides. The three PSA-2 polypeptides were purified from cultured promastigotes by a combination of detergent phase separation and monoclonal antibody affinity chromatography. Intraperitoneal vaccination of C3H/He mice with PSA-2 with Corynebacterium parvum as an adjuvant resulted in complete protection from lesion development after challenge infection with virulent L. major. Significant protection was also obtained in the genetically susceptible BALB/cH-2k and BALB/c mice. One of the PSA-2 genes was cloned and expressed in both Escherichia coli and Leishmania mexicana promastigotes. Vaccination with the recombinant PSA-2 purified from E. coli did not confer protection, in contrast to the L. mexicana-derived recombinant PSA-2, which provided excellent protection. CD4+ T cells isolated from the spleens of vaccinated mice produced large amounts of gamma interferon but no detectable interleukin 4 upon stimulation with PSA-2 in vitro. Limiting dilution analysis showed a marked increase in the precursor frequency of PSA-2-specific gamma interferon-secreting CD4+ T cells. No substantial change in precursor frequency was observed for interleukin 4-secreting T cells in the vaccinated mice. A CD4+ PSA-2 specific T-cell line generated from splenocytes of a vaccinated mouse produces a cytokine pattern consistent with a TH1 phenotype. Intravenous injection of this line into naive mice reduced significantly the parasite burden upon challenge infection. Taken together, the data suggest that vaccination with PSA-2 induces a TH1 type of immune response which protects mice from L. major infection. Moreover, a single recombinant PSA-2 polypeptide derived from a genomic clone can also vaccinate, provided that the structural form of the antigen is near native. PMID:7591056

  14. Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways

    PubMed Central

    Morgan, Meredith A.; Lawrence, Theodore S.

    2015-01-01

    DNA double-strand breaks are the critical lesions responsible for the majority of ionizing radiation-induced cell killing. Thus, the ability of tumor cells to elicit a DNA damage response following radiation, via activation of DNA repair and cell cycle checkpoints, promotes radiation resistance and tumor cell survival. Consequently, agents which target these DNA damage response pathways are being developed to overcome radiation resistance. Overall, these agents are effective radiosensitizers; however, their mechanisms of tumor cell selectivity are not fully elucidated. In this review, we will focus on the crucial radiation-induced DNA damage responses as well as clinical and translational advances with agents designed to inhibit these responses. Importantly, we describe how synthetic lethality can provide tumor cell selective radiosensitization by these agents and expand the therapeutic window for DNA damage response-targeted agents used in combination with radiation therapy. PMID:26133775

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

    PubMed

    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.

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

    PubMed

    Lin, Ya-Fen; Aarts, Mark G M

    2012-10-01

    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 metal-hypertolerant hyperaccumulator species, each having different molecular mechanisms to accomplish their resistance/tolerance to metal stress or reduce the negative consequences of metal toxicity. Plant responses to heavy metals are molecularly regulated in a process called metal homeostasis, which also includes regulation of the metal-induced reactive oxygen species (ROS) signaling pathway. ROS generation and signaling plays an important duel role in heavy metal detoxification and tolerance. In this review, we will compare the different molecular mechanisms of nutritional (Zn) and non-nutritional (Cd) metal homeostasis between metal-sensitive and metal-adapted species. We will also include the role of metal-induced ROS signal transduction in this comparison, with the aim to provide a comprehensive overview on how plants cope with Zn/Cd stress at the molecular level. PMID:22903262

  17. Real-time molecular monitoring of chemical environment in obligate anaerobes during oxygen adaptive response

    PubMed Central

    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.

    2009-01-01

    Determining the transient chemical properties of the intracellular environment can elucidate the paths through which a biological system adapts to changes in its environment, for example, the mechanisms that 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 bond structures in their cellular water. We observed a sequence of well orchestrated 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. PMID:19541631

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

    SciTech Connect

    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.

  19. A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum

    PubMed Central

    Zhu, Fang; Parthasarathy, R.; Bai, Hua; Woithe, Katharina; Kaussmann, Martin; Nauen, Ralf; Harrison, Douglas A.; Palli, Subba R.

    2010-01-01

    Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared with its expression in the deltamethrin-susceptible Lab-S strain. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6BQ9 and transgenic expression of CYP6BQ9 in Drosophila melanogaster showed that CYP6BQ9 confers deltamethrin resistance. Furthermore, CYP6BQ9 enzyme expressed in baculovirus metabolizes deltamethrin to 4-hydroxy deltamethrin. Strikingly, we also found that unlike many P450 genes involved in insecticide resistance that were reported previously, CYP6BQ9 is predominantly expressed in the brain, a part of the central nervous system (CNS) containing voltage-gated sodium channels targeted by deltamethrin. Taken together, the current studies on the brain-specific insect P450 involved in deltamethrin resistance shed new light on the understanding of the molecular basis and evolution of insecticide resistance. PMID:20410462

  20. A brain-specific cytochrome P450 responsible for the majority of deltamethrin resistance in the QTC279 strain of Tribolium castaneum.

    PubMed

    Zhu, Fang; Parthasarathy, R; Bai, Hua; Woithe, Katharina; Kaussmann, Martin; Nauen, Ralf; Harrison, Douglas A; Palli, Subba R

    2010-05-11

    Cytochrome P450-mediated detoxification is one of the most important mechanisms involved in insecticide resistance. However, the molecular basis of this mechanism and the physiological functions of P450s associated with insecticide resistance remain largely unknown. Here, we exploited the functional genomics and reverse genetic approaches to identify and characterize a P450 gene responsible for the majority of deltamethrin resistance observed in the QTC279 strain of Tribolium castaneum. We used recently completed whole-genome sequence of T. castaneum to prepare custom microarrays and identified a P450 gene, CYP6BQ9, which showed more than a 200-fold higher expression in the deltamethrin-resistant QTC279 strain when compared with its expression in the deltamethrin-susceptible Lab-S strain. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression of CYP6BQ9 and transgenic expression of CYP6BQ9 in Drosophila melanogaster showed that CYP6BQ9 confers deltamethrin resistance. Furthermore, CYP6BQ9 enzyme expressed in baculovirus metabolizes deltamethrin to 4-hydroxy deltamethrin. Strikingly, we also found that unlike many P450 genes involved in insecticide resistance that were reported previously, CYP6BQ9 is predominantly expressed in the brain, a part of the central nervous system (CNS) containing voltage-gated sodium channels targeted by deltamethrin. Taken together, the current studies on the brain-specific insect P450 involved in deltamethrin resistance shed new light on the understanding of the molecular basis and evolution of insecticide resistance.

  1. Plasmin Is the Major Protease Responsible for Processing PDGF-C in the Vitreous of Patients with Proliferative Vitreoretinopathy

    PubMed Central

    Lei, Hetian; Velez, Gisela; Hovland, Peter; Hirose, Tatsuo; Kazlauskas, Andrius

    2011-01-01

    Purpose Proliferative vitreoretinopathy (PVR) is the primary cause of failure of retinal reattachment surgery. Growth factors such as platelet-derived growth factor (PDGF) are strongly associated with PVR. Of the five PDGF family members, PDGF-C predominates in the vitreous of experimental and clinical PVR. PDGF-C is secreted as a latent protein that requires proteolytic processing for activation. Although tissue plasminogen activator (tPA) is primarily responsible for processing PDGF-C in cultured cells, it constitutes a minority of the processing activity in the vitreous of experimental animals and in patients with PVR. Identifying the major PDGF-C processing protease was the purpose of this study. Methods The presence of serum proteins in the vitreous was detected by Coomassie blue staining and Western blotting. PDGF-C processing activity was detected in an in vitro processing assay using either native or recombinant PDGF-C as the substrate. Plasmin activity was blocked using α2-plasmin inhibitor. Phosphorylation of the PDGF receptor (PDGFR) was monitored by antiphosphotyrosine Western blotting. Vitreous specimens were collected from experimental rabbits or from patients undergoing vitrectomy to repair retinal detachment or for other reasons. Results A number of prominent serum proteins (albumin and IgG) were detected in the vitreous of all patients undergoing retinal surgery. The level of these proteins markedly increased in the vitreous of rabbits as they developed PVR. These observations suggested that serum-borne proteases are also likely to be present in the vitreous. Indeed, plasmin (a protease capable of processing PDGF-C) was present in the vitreous from PVR rabbits and retinal surgery patients. Plasmin was dramatically more effective than tPA in processing PDGF-C in an in vitro assay. Blocking plasmin activity eliminated most of the processing activity in the vitreous of patients and rabbits with PVR. Conclusions Plasmin was the major PDGF-C processing

  2. Association of ARRB1 polymorphisms with the risk of major depressive disorder and with treatment response to mirtazapine.

    PubMed

    Chang, Hun Soo; Won, Eun Soo; Lee, Hwa-Young; Ham, Byung-Joo; Kim, Yong-Gu; Lee, Min-Soo

    2015-05-01

    β-Arrestin 1 is known to be involved in the pathophysiology of major depressive disorder (MDD) and in the underlying mechanism of action of antidepressant therapies. After we screened 39 ARRB1 polymorphisms, we investigated the associations of seven ARRB1 single-nucleotide polymorphisms (SNPs) with the risk of MDD in 270 patients with MDD and 204 normal subjects, and with mirtazapine treatment response in patients with MDD. The genotype distributions of -132C>T and IVS1+85T>C showed significant deviations from Hardy-Weinberg equilibrium in patients with MDD but not in normal subjects. After four and 12 weeks of mirtazapine treatment, the proportion of haplotype 1 (ht1) carriers was significantly higher in remitters than in non-remitters after corrections for multiple comparisons (corrected p=0.006 and 0.014 at four and 12 weeks, respectively). After eight and 12 weeks of treatment, scores on the 21-item Hamilton Depression Rating Scale (HAMD21) were significantly lower in patients with MDD with ARRB1 ht1 than in those without ht1. Similarly, after 8 and 12 weeks of treatment, the percent reduction in HAMD21 scores was significantly higher in patients with MDD with ARRB1 ht1 than in those without ht1. The ARRB1 polymorphisms represent promising genetic markers for the prediction of treatment responses to mirtazapine. PMID:25294870

  3. Association Study of Genotype by Depressive Response during Acute Tryptophan Depletion in Subjects Recovered from Major Depression

    PubMed Central

    Moreno, Francisco A.; Erickson, Robert P.; Garriock, Holly A.; Gelernter, Joel; Mintz, Jim; Oas-Terpstra, Jennifer; Davies, Marilyn A.; Delgado, Pedro L.

    2015-01-01

    Purpose To study the brief and reversible mood response to acute tryptophan depletion (ATD) as a trait marker in subjects considered at risk for major depressive disorder (MDD). Procedures ATD was administered to 64 subjects (54 European-Americans and 10 from other races) with a personal and family history of MDD. They were in remission and had been medication-free for at least 3 months. Subjects were randomly assignment to an active or sham condition in a double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models. Results Compared to the sham controls, active ATD caused modest depressive changes showing significant main effects of test condition (χ2 = 5.14, d.f. = 1, p = 0.023) and time (χ2 = 12.22, d.f. = 3, p = 0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with the HTR2A rs6313 CC genotype had significantly higher HDRS scores during ATD (χ2 = 11.72, d.f. = 1, p = 0.0006). Conclusions ATD may help identifying the biological subtypes of MDD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes. PMID:26528486

  4. Relation between relative growth rate, endogenous gibberellins, and the response to applied gibberellic acid for Plantago major.

    PubMed

    Dijkstra, P; Reegen, H; Kuiper, P J

    1990-08-01

    Relationships between relative growth rate (RGR), endogenous gibberellin (GA) concentration and the response to application of gibberellic acid (GA(3) ) were studied for two inbred lines of Plantago major L., which differed in RGR. A4, the fast-growing inbred line, had a higher free GA concentration than the slow-growing W9, as analyzed by enzyme immunoassay. GA(3) application increased total plant weight and RGR(3) particularly for the slow-growing line. Chlorophyll a content and photosynthetic activity per unit leaf area were decreased, while transpiration rate was unaffected by GA(3) application. The increase in RGR by GA(3) application was associated with an increased leaf weight ratio; specific leaf area and percentage of dry matter in the leaves were only temporarily affected. Root respiration rate per unit dry weight was unaffected. The correlation between low RGR, low GA concentration and high responsiveness to applied GA(3) supports the contention that gibberellins are involved in the regulation of RGR. However, the transient influence of GA(3) application on some growth components suggests the involvement of other regulatory factors in addition to GA.

  5. Presence and molecular characterization of the major serovars of Listeria monocytogenes in ten Sardinian fermented sausage processing plants.

    PubMed

    Meloni, Domenico; Consolati, Simonetta Gianna; Mazza, Roberta; Mureddu, Anna; Fois, Federica; Piras, Francesca; Mazzette, Rina

    2014-08-01

    The aim of the present study was to investigate the occurrence of Listeria monocytogenes in ten Sardinian fermented sausage processing plants. A total of 230 samples were collected and 40 L. monocytogenes isolates were obtained and subjected to serotyping and investigated for the presence of ten virulence-associated genes using multiplex PCR assays. The isolates were further subjected to PFGE and investigated for their adhesion abilities in polystyrene microtiter plates. L. monocytogenes was found in 6% of food contact surfaces, in sausages at the end of acidification (3%) and ripening (8%). Serotyping revealed the presence of four serovars: 1/2c (37.5%), 1/2b (27.5%), 4b (22.5%) and 1/2a (12.5%). All virulence-associated genes were detected in 67.5% of the isolates. Isolates from processing environment, semi-processed and finished products showed high pulsotype diversity and the majority of isolates presented weak adhesion capability. The detection of the pathogen in fermented sausages confirms the ability of L. monocytogenes to overcome the hurdles of the manufacturing process. PMID:24769142

  6. Presence and molecular characterization of the major serovars of Listeria monocytogenes in ten Sardinian fermented sausage processing plants.

    PubMed

    Meloni, Domenico; Consolati, Simonetta Gianna; Mazza, Roberta; Mureddu, Anna; Fois, Federica; Piras, Francesca; Mazzette, Rina

    2014-08-01

    The aim of the present study was to investigate the occurrence of Listeria monocytogenes in ten Sardinian fermented sausage processing plants. A total of 230 samples were collected and 40 L. monocytogenes isolates were obtained and subjected to serotyping and investigated for the presence of ten virulence-associated genes using multiplex PCR assays. The isolates were further subjected to PFGE and investigated for their adhesion abilities in polystyrene microtiter plates. L. monocytogenes was found in 6% of food contact surfaces, in sausages at the end of acidification (3%) and ripening (8%). Serotyping revealed the presence of four serovars: 1/2c (37.5%), 1/2b (27.5%), 4b (22.5%) and 1/2a (12.5%). All virulence-associated genes were detected in 67.5% of the isolates. Isolates from processing environment, semi-processed and finished products showed high pulsotype diversity and the majority of isolates presented weak adhesion capability. The detection of the pathogen in fermented sausages confirms the ability of L. monocytogenes to overcome the hurdles of the manufacturing process.

  7. Identification and molecular analysis of a multigene family encoding calliphorin, the major larval serum protein of Calliphora vicina

    PubMed Central

    Schenkel, Heide; Kejzlarová-Lepesant, Jana; Berreur, Paul; Moreau, Jacques; Scheller, Klaus; Brègègére, François; Lepesant, Jean-Antoine

    1985-01-01

    A library of Calliphora vicina genomic DNA was constructed in the λEMBL3 vector and screened for recombinant phages containing chromosomal segments encoding calliphorin, the major larval serum protein (LSP) of Calliphora. A large series of recombinants hybridizing with in vitro labelled poly(A)+ RNA from Calliphora larval fat bodies and with specific probes derived from the LSP-1 genes of Drosophila melanogaster was isolated. Five of these phages, chosen at random, were shown by hybrid selection to retain calliphorin mRNA specifically. Eleven calliphorin mRNA-homologous regions were located on restriction maps of these phages by hybridization with 5' end-labelled poly(A)+ RNA from Calliphora larval fat bodies. Each phage contains at least two calliphorin genes arranged in direct repeat orientation and seperated by 3.5–5 kb intergenic regions. The genes display similar but not identical restriction patterns. Filter hybridization and heteroduplex analysis indicate that they share a detectable homology with the LSP-1β gene of D. melanogaster. Whole genome Southern analysis showed that these genes belong to a large family of closely related calliphorin genes which were found by in situ hybridization to polytene chromosomes of trichogen cells to be clustered in region 4a of chromosome 2 of Calliphora vicina. ImagesFig. 1.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8. PMID:16453643

  8. Spectroscopic studies on chemical- and photo-responsive molecular machines and their bio-applications

    NASA Astrophysics Data System (ADS)

    Lau, Yuen Agnes

    2011-07-01

    The four chapters presented in this dissertation describe how various spectroscopic techniques are used: 1) to study the operation of molecular machines in solution, 2) to track the operation of molecular machines inside a single cell, and 3) to investigate the photo-decomposition pathway of a biological chromophore. Recent advances in nanotechnology have enriched the development of nano-scale molecular assemblies to be used as delivery platforms for biologically relevant molecules. Among all the molecular assemblies, molecular machines that are incorporated onto various domains of mesoporous silica nanoparticles (MSN) hold considerable potential as a reliable delivery system. Because the ease of functionalization enables chemical or photo-responsive molecular moieties to be covalently attached to the silica framework, these molecular assemblies, with defined mechanized properties, can perform specific functions under external stimuli (pH, redox, or light). While the primary function of these molecular machines is to deliver stored cargo molecules, the means of activation and the motif in which they operate are different. In the first and second chapters of this dissertation, two types of molecular machines, nanovalves and nanoimpellers, and their operations are studied. The ability to continuously monitor and image progression of molecular-based biological events in real-time can enhance our understanding of intracellular processes upon drug, protein and nucleic acid delivery. Using the photo-activated nanoimpeller described in the second chapter, the third chapter explores how it can be used to transport a nuclear staining agent, PI, inside a single cell. Nanoimpellers are made by functionalizing azobenzene molecules to the internal pore surface of MSN. The continuous cis/trans isomerizations are set in motion upon laser illumination at optimal wavelength(s), which facilitate cargo molecules to be expelled from the pores to the surrounding medium. By refining a

  9. A Molecular Profile of the Endothelial Cell Response to Ionizing Radiation.

    PubMed

    Himburg, Heather A; Sasine, Joshua; Yan, Xiao; Kan, Jenny; Dressman, Holly; Chute, John P

    2016-08-01

    Ionizing radiation exposure can cause acute radiation sickness (ARS) by damaging the hematopoietic compartment. Radiation damages quiescent hematopoietic stem cells (HSCs) and proliferating hematopoietic cells, resulting in neutropenia, thrombocytopenia and increased risk for long-term hematopoietic dysfunction and myelodysplasia. While some aspects of the hematopoietic response to radiation injury are intrinsic to hematopoietic cells, the recovery of the HSC pool and overall hematopoiesis is also dependent on signals from bone marrow endothelial cells (BM ECs) within the HSC vascular niche. The precise mechanisms through which BM ECs regulate HSC regeneration remain unclear. Characterization of the altered EC gene expression that occurs in response to radiation could provide a roadmap to the discovery of EC-derived mechanisms that regulate hematopoietic regeneration. Here, we show that 5 Gy total-body irradiation substantially alters the expression of numerous genes in BM ECs within 24 h and this molecular response largely resolves by day 14 postirradiation. Several unique and nonannotated genes, which encode secreted proteins were upregulated and downregulated in ECs in response to radiation. These results highlight the complexity of the molecular response of BM ECs to ionizing radiation and identify several candidate mechanisms that should be prioritized for functional analysis in models of hematopoietic injury and regeneration. PMID:27387861

  10. Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia

    PubMed Central

    SASSI, A; LOUZIR, H; BEN SALAH, A; MOKNI, M; BEN OSMAN, A; DELLAGI, K

    1999-01-01

    Resistance to Leishmania parasite infection requires the development of a cellular immune response that activates macrophage leishmanicidal activity. In this study we have investigated the lymphoproliferative responses and in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from individuals living in an endemic area for L. major infection in Tunisia. The results were compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven individuals were included in the study: 22 persons (age range 9–60 years) who developed, 2 years before the present study, a parasitologically confirmed localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45 individuals (age range 18–20 years) born and living in the same area, with no previous history of LCL. LST was positive (skin induration ≥ 5 mm) in 20/22 cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+ individuals expressed vigorous Leishmania-specific lymphoproliferative responses associated with in vitro production of interferon-gamma (IFN-γ) but not IL-4. Interestingly, IL-10 was detected in parallel with the highest levels of IFN-γ in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without history of LCL. Our results showed a 98% concordance between the DTH reaction assessed by LST and the in vitro proliferative assay induced by soluble leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis did not show any significant difference of the immune memory to parasite antigens developed by patients who had overt cutaneous leishmaniasis and those who had apparently asymptomatic infection. PMID:10209516

  11. The Plasma Membrane H+-ATPase AHA1 Plays a Major Role in Stomatal Opening in Response to Blue Light.

    PubMed

    Yamauchi, Shota; Takemiya, Atsushi; Sakamoto, Tomoaki; Kurata, Tetsuya; Tsutsumi, Toshifumi; Kinoshita, Toshinori; Shimazaki, Ken-Ichiro

    2016-08-01

    Stomata open in response to a beam of weak blue light under strong red light illumination. A blue light signal is perceived by phototropins and transmitted to the plasma membrane H(+)-ATPase that drives stomatal opening. To identify the components in this pathway, we screened for mutants impaired in blue light-dependent stomatal opening. We analyzed one such mutant, provisionally named blus2 (blue light signaling2), and found that stomatal opening in leaves was impaired by 65%, although the magnitude of red light-induced opening was not affected. Blue light-dependent stomatal opening in the epidermis and H(+) pumping in guard cell protoplasts were inhibited by 70% in blus2 Whole-genome resequencing identified a mutation in the AHA1 gene of the mutant at Gly-602. T-DNA insertion mutants of AHA1 exhibited a similar phenotype to blus2; this phenotype was complemented by the AHA1 gene. We renamed blus2 as aha1-10 T-DNA insertion mutants of AHA2 and AHA5 did not show any impairment in stomatal response, although the transcript levels of AHA2 and AHA5 were higher than those of AHA1 in wild-type guard cells. Stomata in ost2, a constitutively active AHA1 mutant, did not respond to blue light. A decreased amount of H(+)-ATPase in aha1-10 accounted for the reduced stomatal blue light responses and the decrease was likely caused by proteolysis of misfolded AHA1. From these results, we conclude that AHA1 plays a major role in blue light-dependent stomatal opening in Arabidopsis and that the mutation made the AHA1 protein unstable in guard cells. PMID:27261063

  12. The Effect of Crosslinking on the Microscale Stress Response and Molecular Deformations in Actin Networks

    NASA Astrophysics Data System (ADS)

    Gurmessa, Bekele; Fitzpatrick, Robert; Valdivia, Jonathon; Anderson, Rae M. R.

    Actin, the most abundant protein in eukaryotic cells, is a semi-flexible biopolymer in the cytoskeleton that plays a crucial structural and mechanical role in cell stability, motion and replication, as well as muscle contraction. Most of these mechanically driven structural changes in cells stem from the complex viscoelastic nature of entangled actin networks and the presence of a myriad of proteins that cross-link actin filaments. Despite their importance, the mechanical response of actin networks is not yet well understood, particularly at the molecular level. Here, we use optical trapping - coupled with fluorescence microscopy - to characterize the microscale stress response and induced filament deformations in entangled and cross-linked actin networks subject to localized mechanical perturbations. In particular, we actively drive a microsphere 10 microns through an entangled or cross- linked actin network at a constant speed and measure the resistive force that the deformed actin filaments exert on the bead during and following strain. We simultaneously visualize and track individual sparsely-labeled actin filaments to directly link force response to molecular deformations, and map the propagation of the initially localized perturbation field throughout the rest of the network (~100 um). By varying the concentration of actin and cross-linkers we directly determine the role of crosslinking and entanglements on the length and time scales of stress propagation, molecular deformation and relaxation mechanisms in actin networks.

  13. Polymorphism and Elastic Response of Molecular Materials from First Principles: How Hard Can it Be?

    NASA Astrophysics Data System (ADS)

    Reilly, Anthony; Tkatchenko, Alexandre

    2014-03-01

    Molecular materials are of great fundamental and applied importance in science and industry, with numerous applications in pharmaceuticals, electronics, sensing, and catalysis. A key challenge for theory has been the prediction of their stability, polymorphism and response to perturbations. While pairwise models of van der Waals (vdW) interactions have improved the ability of density functional theory (DFT) to model these systems, substantial quantitative and even qualitative failures remain. In this contribution we show how a many-body description of vdW interactions can dramatically improve the accuracy of DFT for molecular materials, yielding quantitative description of stabilities and polymorphism for these challenging systems. Moreover, the role of many-body vdW interactions goes beyond stabilities to response properties. In particular, we have studied the elastic properties of a series of molecular crystals, finding that many-body vdW interactions can account for up to 30% of the elastic response, leading to quantitative and qualitative changes in elastic behavior. We will illustrate these crucial effects with the challenging case of the polymorphs of aspirin, leading to a better understanding of the conflicting experimental and theoretical studies of this system.

  14. Molecular Signatures of the Evolving Immune Response in Mice following a Bordetella pertussis Infection

    PubMed Central

    Raeven, René H. M.; Brummelman, Jolanda; Pennings, Jeroen L. A.; Nijst, Olaf E. M.; Kuipers, Betsy; Blok, Laura E. R.; Helm, Kina; van Riet, Elly; Jiskoot, Wim; van Els, Cecile A. C. M.; Han, Wanda G. H.; Kersten, Gideon F. A.; Metz, Bernard

    2014-01-01

    Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses. PMID:25137043

  15. Genetic and molecular bases of photoperiod responses of flowering in soybean.

    PubMed

    Watanabe, Satoshi; Harada, Kyuya; Abe, Jun

    2012-01-01

    Flowering is one of the most important processes involved in crop adaptation and productivity. A number of major genes and quantitative trait loci (QTLs) for flowering have been reported in soybean (Glycine max). These genes and QTLs interact with one another and with the environment to greatly influence not only flowering and maturity but also plant morphology, final yield, and stress tolerance. The information available on the soybean genome sequence and on the molecular bases of flowering in Arabidopsis will undoubtedly facilitate the molecular dissection of flowering in soybean. Here, we review the present status of our understanding of the genetic and molecular mechanisms of flowering in soybean. We also discuss our identification of orthologs of Arabidopsis flowering genes from among the 46,367 genes annotated in the publicly available soybean genome database Phytozome Glyma 1.0. We emphasize the usefulness of a combined approach including QTL analysis, fine mapping, and use of candidate gene information from model plant species in genetic and molecular studies of soybean flowering. PMID:23136492

  16. Sunitinib malate and figitumumab in solitary fibrous tumor: patterns and molecular bases of tumor response.

    PubMed

    Stacchiotti, Silvia; Negri, Tiziana; Palassini, Elena; Conca, Elena; Gronchi, Alessandro; Morosi, Carlo; Messina, Antonella; Pastorino, Ugo; Pierotti, Marco A; Casali, Paolo G; Pilotti, Silvana

    2010-05-01

    Antiangiogenic treatment activity has been reported in solitary fibrous tumor (SFT), a rare and little chemosensitive sarcoma. We explored the activity of sunitinib malate (SM) in SFT and studied receptor tyrosine kinase (RTK) activation profile. Eleven patients with progressive metastatic SFT resistant to chemotherapy were treated with continuous-dosing 37.5 mg/d SM on a named-use basis. One of them also received the insulin-like growth factor I receptor (IGFIR) inhibitor figitumumab after developing secondary resistance to SM. Besides, biochemical, molecular, and fluorescence in situ hybridization analyses were done in eight naïve SFTs whose cryopreserved material was available to clarify RTK upstream and downstream signaling. In two cases treated with SM and belonging to the naïve series, both pretreatment and posttreatment samples were available. Ten patients were evaluable for response to SM. The best response according to the Choi criteria was six partial response (all with Response Evaluation Criteria in Solid Tumors stable disease), one stable disease, and three progressive disease. Responses lasted >6 months in five patients. The eight naïve samples showed high expression/phosphorylation of PDGFRB, epidermal growth factor receptor, and IGFIR/IR, in the presence of their cognate ligands. Downstream pathways revealed expression/activation of Akt, extracellular signal-regulated kinase 1-2 and, closely related to SFT subtypes, of S6 and 4E-BP1. In two patients, whose pretreatment and posttreatment clinical and molecular status were available, biochemical data confirmed the activity of SM, although they also suggested a possible time-dependent shift of dominant RTK from PDGFRB to IGFIR/insulin receptor. A Response Evaluation Criteria in Solid Tumors partial response to figitumumab corroborated these findings. SM has antitumor activity in SFT, possibly through a PDGFRB-mediated mechanism, but treatments with IGFIR/insulin receptor and possibly epidermal

  17. Differential regulation of sorbitol and sucrose loading into the phloem of Plantago major in response to salt stress.

    PubMed

    Pommerrenig, Benjamin; Papini-Terzi, Flavia Stal; Sauer, Norbert

    2007-06-01

    Several plant families generate polyols, the reduced form of monosaccharides, as one of their primary photosynthetic products. Together with sucrose (Suc) or raffinose, these polyols are used for long-distance allocation of photosynthetically fixed carbon in the phloem. Many species from these families accumulate these polyols under salt or drought stress, and the underlying regulation of polyol biosynthetic or oxidizing enzymes has been studied in detail. Here, we present results on the differential regulation of genes that encode transport proteins involved in phloem loading with sorbitol and Suc under salt stress. In the Suc- and sorbitol-translocating species Plantago major, the mRNA levels of the vascular sorbitol transporters PmPLT1 and PmPLT2 are rapidly up-regulated in response to salt treatment. In contrast, mRNA levels for the phloem Suc transporter PmSUC2 stay constant during the initial phase of salt treatment and are down-regulated after 24 h of salt stress. This adaptation in phloem loading is paralleled by a down-regulation of mRNA levels for a predicted sorbitol dehydrogenase (PmSDH1) in the entire leaf and of mRNA levels for a predicted Suc phosphate synthase (PmSPS1) in the vasculature. Analyses of Suc and sorbitol concentrations in leaves, in enriched vascular tissue, and in phloem exudates of detached leaves revealed an accumulation of sorbitol and, to a lesser extent, of Suc within the leaves of salt-stressed plants, a reduced rate of phloem sap exudation after NaCl treatment, and an increased sorbitol-to-Suc ratio within the phloem sap. Thus, the up-regulation of PmPLT1 and PmPLT2 expression upon salt stress results in a preferred loading of sorbitol into the phloem of P. major.

  18. Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea.

    PubMed

    Garg, Rohini; Shankar, Rama; Thakkar, Bijal; Kudapa, Himabindu; Krishnamurthy, Lakshmanan; Mantri, Nitin; Varshney, Rajeev K; Bhatia, Sabhyata; Jain, Mukesh

    2016-01-01

    Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea. PMID:26759178

  19. Transcriptome analyses reveal genotype- and developmental stage-specific molecular responses to drought and salinity stresses in chickpea

    PubMed Central

    Garg, Rohini; Shankar, Rama; Thakkar, Bijal; Kudapa, Himabindu; Krishnamurthy, Lakshmanan; Mantri, Nitin; Varshney, Rajeev K.; Bhatia, Sabhyata; Jain, Mukesh

    2016-01-01

    Drought and salinity are the major factors that limit chickpea production worldwide. We performed whole transcriptome analyses of chickpea genotypes to investigate the molecular basis of drought and salinity stress response/adaptation. Phenotypic analyses confirmed the contrasting responses of the chickpea genotypes to drought or salinity stress. RNA-seq of the roots of drought and salinity related genotypes was carried out under control and stress conditions at vegetative and/or reproductive stages. Comparative analysis of the transcriptomes revealed divergent gene expression in the chickpea genotypes at different developmental stages. We identified a total of 4954 and 5545 genes exclusively regulated in drought-tolerant and salinity-tolerant genotypes, respectively. A significant fraction (~47%) of the transcription factor encoding genes showed differential expression under stress. The key enzymes involved in metabolic pathways, such as carbohydrate metabolism, photosynthesis, lipid metabolism, generation of precursor metabolites/energy, protein modification, redox homeostasis and cell wall component biogenesis, were affected by drought and/or salinity stresses. Interestingly, transcript isoforms showed expression specificity across the chickpea genotypes and/or developmental stages as illustrated by the AP2-EREBP family members. Our findings provide insights into the transcriptome dynamics and components of regulatory network associated with drought and salinity stress responses in chickpea. PMID:26759178

  20. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling

    PubMed Central

    Juntawong, Piyada; Sirikhachornkit, Anchalee; Pimjan, Rachaneeporn; Sonthirod, Chutima; Sangsrakru, Duangjai; Yoocha, Thippawan; Tangphatsornruang, Sithichoke; Srinives, Peerasak

    2014-01-01

    Jatropha (Jatropha curcas) is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq). The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future. PMID:25520726

  1. Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling.

    PubMed

    Juntawong, Piyada; Sirikhachornkit, Anchalee; Pimjan, Rachaneeporn; Sonthirod, Chutima; Sangsrakru, Duangjai; Yoocha, Thippawan; Tangphatsornruang, Sithichoke; Srinives, Peerasak

    2014-01-01

    Jatropha (Jatropha curcas) is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq). The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.

  2. COPD disease severity and innate immune response to pathogen-associated molecular patterns

    PubMed Central

    Fan, Vincent S; Gharib, Sina A; Martin, Thomas R; Wurfel, Mark M

    2016-01-01

    The airways of COPD patients are often colonized with bacteria leading to increased airway inflammation. This study sought to determine whether systemic cytokine responses to microbial pathogen-associated molecular patterns (PAMPs) are increased among subjects with severe COPD. In an observational cross-sectional study of COPD subjects, PAMP-induced cytokine responses were measured in whole blood ex vivo. We used PAMPs derived from microbial products recognized by toll-like receptors 1, 2, 4, 5, 6, 7, and 8. Patterns of cytokine response to PAMPs were assessed using hierarchical clustering. One-sided Student’s t-tests were used to compare PAMP-induced cytokine levels in blood from patients with and without severe COPD, and for subjects with and without chronic bronchitis. Of 28 male patients, 12 had moderate COPD (FEV1 50%–80%) and 16 severe COPD (FEV1 <50%); 27 participants provided data on self-reported chronic bronchitis, of which 15 endorsed chronic bronchitis symptoms and 12 did not. Cytokine responses to PAMPs in severe COPD were generally lower than in subjects with milder COPD. This finding was particularly strong for PAMP-induced interleukin (IL)-10, granulocyte colony stimulating factor, and IL-1β. Subjects with chronic bronchitis showed higher PAMP-induced IL-1RA responses to most of the PAMPs evaluated. COPD patients with more severe disease demonstrated a diminished cytokine response to PAMPs, suggesting that chronic colonization with bacteria may dampen the systemic innate immune response. PMID:27019597

  3. Major depression.

    PubMed

    Bentley, Susan M; Pagalilauan, Genevieve L; Simpson, Scott A

    2014-09-01

    Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co-morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered.

  4. Long-term activation of the pro-coagulant response after neoadjuvant chemoradiation and major cancer surgery

    PubMed Central

    Byrne, M; Reynolds, J V; O'Donnell, J S; Keogan, M; White, B; Byrne, M; Murphy, S; Maher, S G; Pidgeon, G P

    2009-01-01

    Background: The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy is increasingly being used as standard treatment for localised gastrointestinal cancer. The aim of this study was to examine the markers of pro-coagulation response and VTE risk in an exemplar multimodal model of pre-operative combination chemotherapy and radiation therapy, followed by complex cancer surgery. Methods: Consecutive patients (n=36) with localised oesophageal cancer were studied at baseline after the first and second cycles of chemoradiation, and on post-operative days 1–28, and at 3, 6 and 9 months. Factors regulating the pro- and anti-coagulant response, as well as pro-inflammatory markers including NFκB activation in peripheral blood mononuclear cells, were examined. All patients received enoxaparin 40 mg s.c. postoperatively up to discharge, and underwent pulmonary CT-pulmonary angiography and venography on day 10 postoperatively. Results: Four (11%) non-fatal thromboembolic events were documented, all after hospital discharge. Neoadjuvant therapy before surgery activated factor VIII (FVIII) and pro-inflammatory NFκB, and increased D-dimers, pro-thrombin fragment 1+2 (F1+2) and the thrombin-anti-thrombin complex (TAT). Surgery significantly (P<0.05) increased pro-thrombin time (PT), activated partial thromboplastin time, fibrinogen, D-dimers, TAT, F1+2 and FVIII up to 6 months. Conclusion: These data highlight the linked pro-coagulant and immunoinflammatory pathways in the multimodal management of oesophageal cancer, and suggest that the duration of current standard thromboprophylaxis regimens warrants further study. PMID:19953092

  5. Do great tits (Parus major) suppress basal metabolic rate in response to increased perceived predation danger? A field experiment.

    PubMed

    Mathot, Kimberley J; Abbey-Lee, Robin N; Kempenaers, Bart; Dingemanse, Niels J

    2016-10-01

    Several studies have shown that individuals with higher metabolic rates (MRs) feed at higher rates and are more willing to forage in the presence of predators. This increases the acquisition of resources, which in turn, may help to sustain a higher MR. Elevated predation danger may be expected to result in reduced MRs, either as a means of allowing for reduced feeding and risk-taking, or as a consequence of adaptively reducing intake rates via reduced feeding and/or risk-taking. We tested this prediction in free-living great tits (Parus major) using a playback experiment to manipulate perceived predation danger. There was evidence that changes in body mass and BMR differed as a function of treatment. In predator treatment plots, great tits tended to reduce their body mass, a commonly observed response in birds to increased predation danger. In contrast, birds from control treatment plots showed no overall changes in body mass. There was also evidence that great tits from control treatment plots increased their basal metabolic rate (BMR) over the course of the experiment, presumably due to decreasing ambient temperatures over the study period. However, there was no evidence for changes in BMR for birds from predator treatment plots. Although the directions of these results are consistent with the predicted directions of effects, the effects sizes and confidence intervals yield inconclusive support for the hypothesis that great tits would adaptively suppress BMR in response to increased perceived predation risk. The effect size observed in the present study was small (~1%) and would not be expected to result in substantive reductions in feeding rate and/or risk-taking. Whether or not ecological conditions that generate greater energetic stress (e.g. lower food availability, lower ambient temperatures) could produce an effect that produces biologically meaningful reductions in feeding activity and/or risk-taking remains an open question.

  6. Association analysis for corticotropin releasing hormone polymorphisms with the risk of major depressive disorder and the response to antidepressants.

    PubMed

    Chang, Hun Soo; Won, Eunsoo; Lee, Hwa-Young; Ham, Byung-Joo; Lee, Min-Soo

    2015-10-01

    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent neuroendocrine abnormalities observed in patients with major depressive disorder (MDD). The peptide corticotropin-releasing hormone (CRH) is a key mediator for HPA axis function during stress. This study evaluated the associations of CRH polymorphisms with susceptibility to MDD and response to antidepressant treatment, and the gene-environment interaction with stressful life events (SLEs). After screening 31 polymorphisms in the gene encoding CRH, we evaluated the association of polymorphisms with MDD susceptibility in 149 patients with MDD and 193 control subjects; in patients, we also evaluated the response to treatment with antidepressants. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) than were remitters (P = 0.019-0.038), when only patients without SLE were included; however, the association was not significant after correction for multiple comparisons. Additionally, after 4 and 8 weeks of treatment in patients who experienced no SLEs, significantly higher 21-item Hamilton Depression Rating scores were found in MDD subjects who were CRH ht1 homozygotes compared to patients carrying one or no ht1 alleles (P = 0.007 and 0.027 at 4 and 8 weeks, respectively). Although these preliminary observations require further confirmation in future studies, these results on the interaction between CRH haplotypes and SLEs, suggest that CRH ht1 which is moderated by SLEs, may be associated with antidepressant treatment outcomes in patients with MDD. PMID:26055202

  7. Association analysis for corticotropin releasing hormone polymorphisms with the risk of major depressive disorder and the response to antidepressants.

    PubMed

    Chang, Hun Soo; Won, Eunsoo; Lee, Hwa-Young; Ham, Byung-Joo; Lee, Min-Soo

    2015-10-01

    Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent neuroendocrine abnormalities observed in patients with major depressive disorder (MDD). The peptide corticotropin-releasing hormone (CRH) is a key mediator for HPA axis function during stress. This study evaluated the associations of CRH polymorphisms with susceptibility to MDD and response to antidepressant treatment, and the gene-environment interaction with stressful life events (SLEs). After screening 31 polymorphisms in the gene encoding CRH, we evaluated the association of polymorphisms with MDD susceptibility in 149 patients with MDD and 193 control subjects; in patients, we also evaluated the response to treatment with antidepressants. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) than were remitters (P = 0.019-0.038), when only patients without SLE were included; however, the association was not significant after correction for multiple comparisons. Additionally, after 4 and 8 weeks of treatment in patients who experienced no SLEs, significantly higher 21-item Hamilton Depression Rating scores were found in MDD subjects who were CRH ht1 homozygotes compared to patients carrying one or no ht1 alleles (P = 0.007 and 0.027 at 4 and 8 weeks, respectively). Although these preliminary observations require further confirmation in future studies, these results on the interaction between CRH haplotypes and SLEs, suggest that CRH ht1 which is moderated by SLEs, may be associated with antidepressant treatment outcomes in patients with MDD.

  8. Treatment with cathepsin L inhibitor potentiates Th2-type immune response in Leishmania major-infected BALB/c mice.

    PubMed

    Zhang, T; Maekawa, Y; Sakai, T; Nakano, Y; Ishii, K; Hisaeda, H; Dainichi, T; Asao, T; Katunuma, N; Himeno, K

    2001-08-01

    Prior to the activation of CD4 (+) T cells, exogenous proteins must be digested by endo/lysosomal enzymes in antigen-presenting cells (APC) to produce antigenic peptides that are able to be presented on class II molecules of the MHC. Studies described here inspect the functional significance of cathepsin L inhibition for antigen processing and T (h) 1/T (h) 2 differentiation in experimental leishmaniasis. We first demonstrated using in vitro systems that cathepsin L is one of the candidate endo/lysosomal enzymes in processing of soluble Leishmania antigen (SLA) and that its specific inhibitor, CLIK148, modulated the processing of SLA. BALB/c mice are known to be susceptible to infection with Leishmania major. Interestingly, treatment of BALB/c mice with CLIK148 exacerbated the infection by enhancing the development of SLA-specific T (h) 2-type response such as production of IL-4 and generation of T (h) 2-dependent specific IgE/IgG1 antibodies. Moreover, addition of CLIK148 in incubation of a SLA-specific CD4 (+) T cell line with APC up-regulated the production of IL-4. However, CLIK148 did not exert any direct influence on the function of T cells themselves. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APC, resulting in the potentiation of T (h) 2-type immune responses and thus leading to exacerbation of the infection. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.

  9. Do great tits (Parus major) suppress basal metabolic rate in response to increased perceived predation danger? A field experiment.

    PubMed

    Mathot, Kimberley J; Abbey-Lee, Robin N; Kempenaers, Bart; Dingemanse, Niels J

    2016-10-01

    Several studies have shown that individuals with higher metabolic rates (MRs) feed at higher rates and are more willing to forage in the presence of predators. This increases the acquisition of resources, which in turn, may help to sustain a higher MR. Elevated predation danger may be expected to result in reduced MRs, either as a means of allowing for reduced feeding and risk-taking, or as a consequence of adaptively reducing intake rates via reduced feeding and/or risk-taking. We tested this prediction in free-living great tits (Parus major) using a playback experiment to manipulate perceived predation danger. There was evidence that changes in body mass and BMR differed as a function of treatment. In predator treatment plots, great tits tended to reduce their body mass, a commonly observed response in birds to increased predation danger. In contrast, birds from control treatment plots showed no overall changes in body mass. There was also evidence that great tits from control treatment plots increased their basal metabolic rate (BMR) over the course of the experiment, presumably due to decreasing ambient temperatures over the study period. However, there was no evidence for changes in BMR for birds from predator treatment plots. Although the directions of these results are consistent with the predicted directions of effects, the effects sizes and confidence intervals yield inconclusive support for the hypothesis that great tits would adaptively suppress BMR in response to increased perceived predation risk. The effect size observed in the present study was small (~1%) and would not be expected to result in substantive reductions in feeding rate and/or risk-taking. Whether or not ecological conditions that generate greater energetic stress (e.g. lower food availability, lower ambient temperatures) could produce an effect that produces biologically meaningful reductions in feeding activity and/or risk-taking remains an open question. PMID:27342428

  10. Exploring Two Interventions to Promote Graduate Education Majors' Dispositions toward Culturally Responsive Teaching: Taking Action to Address My Shortcomings as a Literacy Teacher Educator

    ERIC Educational Resources Information Center

    Richards, Janet

    2011-01-01

    For five years I have supervised a summer literacy camp that connects graduate education majors with students from diverse ethnicities. Each summer I noted I inadequately challenged the education majors to extend their knowledge, examine their attitudes, and expand their abilities to offer culturally responsive literacy instruction to students in…

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

    PubMed

    Hayashi, Yuya; Heckmann, Lars-Henrik; Simonsen, Vibeke; Scott-Fordsmand, Janeck J

    2013-12-01

    The molecular mechanism of silver nanoparticle (AgNP) toxicity, particularly its temporal aspect, is currently limited in the literature. This study seeks to identify and profile changes in molecular response patterns over time during soil exposure of the earthworm Eisenia fetida to AgNPs (82±27 nm) 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, highlighting the importance of immunological endpoints in nanosilver toxicity. PMID:24041528

  12. Molecular Components of the Sporothrix schenckii Complex that Induce Immune Response.

    PubMed

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Romo-Lozano, Yolanda; López-Romero, Everardo; Ruiz-Baca, Estela

    2016-08-01

    Sporotrichosis is a fungal disease caused by the Sporothrix schenckii complex that includes species such as S. brasiliensis, S. schenckii sensu stricto, S. globosa, S. luriei, S. mexicana, and S. pallida, which exhibit different potentially antigenic molecular components. The immune response of susceptible hosts to control infection and disease caused by these fungi has been little studied. Besides, the fungus-host interaction induces the activation of different types of immune response. This mini-review analyzes and discusses existing reports on the identification and functional characterization of molecules from species of the S. schenckii complex with clinical relevance, and the mechanisms that mediate the type and magnitude of the immune response in experimental models in vivo and in vitro. This knowledge is expected to contribute to the development of protective and therapeutic strategies against sporotrichosis and other mycoses. PMID:27117164

  13. Molecular Components of the Sporothrix schenckii Complex that Induce Immune Response.

    PubMed

    Alba-Fierro, Carlos A; Pérez-Torres, Armando; Toriello, Conchita; Romo-Lozano, Yolanda; López-Romero, Everardo; Ruiz-Baca, Estela

    2016-08-01

    Sporotrichosis is a fungal disease caused by the Sporothrix schenckii complex that includes species such as S. brasiliensis, S. schenckii sensu stricto, S. globosa, S. luriei, S. mexicana, and S. pallida, which exhibit different potentially antigenic molecular components. The immune response of susceptible hosts to control infection and disease caused by these fungi has been little studied. Besides, the fungus-host interaction induces the activation of different types of immune response. This mini-review analyzes and discusses existing reports on the identification and functional characterization of molecules from species of the S. schenckii complex with clinical relevance, and the mechanisms that mediate the type and magnitude of the immune response in experimental models in vivo and in vitro. This knowledge is expected to contribute to the development of protective and therapeutic strategies against sporotrichosis and other mycoses.

  14. Small Molecule Activators of the Heat Shock Response: Chemical Properties, Molecular Targets, and Therapeutic Promise

    PubMed Central

    West, James D.; Wang, Yanyu; Morano, Kevin A.

    2012-01-01

    All cells have developed various mechanisms to respond and adapt to a variety of environmental challenges, including stresses that damage cellular proteins. One such response, the heat shock response (HSR), leads to the transcriptional activation of a family of molecular chaperone proteins that promote proper folding or clearance of damaged proteins within the cytosol. In addition to its role in protection against acute insults, the HSR also regulates lifespan and protects against protein misfolding that is associated with degenerative diseases of aging. As a result, identifying pharmacological regulators of the HSR has become an active area of research in recent years. Here, we review progress made in identifying small molecule activators of the HSR, what cellular targets these compounds interact with to drive response activation, and how such molecules may ultimately be employed to delay or reverse protein misfolding events that contribute to a number of diseases. PMID:22799889

  15. First microscopical and molecular-based characterization of Leishmania major within naturally infected Phlebotomus salehi (Diptera; Psychodidae) in Fars province, southern Iran

    PubMed Central

    DAVAMI, M H; MOTAZEDIAN, M H; KALANTARI, M; ASGARI, Q; BADZOHRE, A; MOHAMMADPOUR, I

    2011-01-01

    Zoonotoc cutaneous leishmaniasis is endemic in several parts of Iran. Jahrom district is one of the most important endemic foci of leishmaniasis located in Fars province, southern Iran. To identify the vectors of leishmaniasis in this area, a total of 349 sandflies were collected during May to August 2009. They were caught from outdoors in five regions of Jahrom district including villages of Mousavieh, Ghotb-Abad, Heydar-Abad, Fath-Abad and Jahrom County. Eleven species of Phlebotomine (three Phlebotomus spp. and eight Sergentomyia spp.) were detected. To determine the sandflies naturally infected by Leishmania spp., 122 female sandflies were dissected and evaluated microscopically using Giemsa-stained slides. Natural infection of 2 out of 38 (5.26%) P. papatasi and 1 out of 8 (12.5%) P. salehi to Leishmania major was confirmed in the region. Sequencing and nested polymerase chain reaction-based detection of Leishmania were carried out to confirm the microscopic findings. Five (13.16%) P. papatasi and two (25%) P. salehi were positive in nested polymerase chain reaction assay. All positive samples were shown 72–76% similarity with L. major Friedlin. On the basis of our knowledge, this is the first molecular detection of L. major within naturally infected P. salehi in this region in southern Iran. PMID:22185942

  16. Comparative study on the ionospheric response to minor and major sudden stratospheric events in the Brazilian equatorial and low latitudes

    NASA Astrophysics Data System (ADS)

    Fagundes, Paulo Roberto; Kavutarapu, Venkatesh; Gil Pillat, Valdir; Vieira, Francisco

    2016-07-01

    The Total electron Content (TEC), derivate from GPS, becomes one of the most powerful techniques to study the space-time ionospheric (F-region) electrodynamics, during the quiet and disturbed periods. The number of GPS stations in Brazil increased significantly during the last few years; currently more than 100 GPS stations are in operation over the Brazilian region. The GPS-TEC values are derived using the differential delay technique from the dual frequency measurements at L1 and L2 frequencies over the considered locations at equatorial and low latitudes. The present study investigates the ionospheric total electron content (GPS-TEC) response in the Southern Hemisphere equatorial and low latitudes, due to major and minor sudden stratospheric warming (SSW) events, which took place during 2009 and 2012. During both the SSW events, the TEC values are depleted to the order of 20-30% all over the Brazil from equator to beyond Equatorial Ionization Anomaly (EIA) regions. In addition, the EIA were suppressed during the SSW events for several days. However, the TEC depletion and EIA suppression lasted for a longer period during SSW-2012 when compared with the SSW-2009; despite the SSW-2012 is considerd as a minor event.

  17. Silencing of the olfactory co-receptor gene in Dendroctonus armandi leads to EAG response declining to major host volatiles

    NASA Astrophysics Data System (ADS)

    Zhang, Ranran; Gao, Guanqun; Chen, Hui

    2016-03-01

    In this study, a polymerase chain reaction (PCR) based on homology genes of Orco was utilized to identify DarmOrco, which is essential for olfaction in D. armandi. The results showed that DarmOrco shares significant sequence homology with Orco proteins had known in other insects. Quantitative real-time PCR (qRT-PCR) analysis suggested that DarmOrco was abundantly expressed in adult D. armandi; by contrast, DarmOrco showed trace amounts of expression level in other stages. Of different tissues, DarmOrco expression level was the highest in the antennae. In order to understand the functional significance of Orco, we injected siRNA of DarmOrco into the conjunctivum between the second and third abdominal segments, and evaluated its expression after siRNA injected for 24 h, 48 h and 72 h. The results of qRT-PCR demonstrated that the reduction of mRNA expression level was significant (~80%) in DarmOrco siRNA-treated D. armandi than in water-injected and non-injected controls. The electroantennogram responses of females and males to 11 major volatiles of its host, were also reduced (30~68% for females; 16~70% for males) in siRNA-treated D. armandi compared with the controls. These results suggest that DarmOrco is crucial in mediating odorant perception.

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

    SciTech Connect

    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. Silencing of the olfactory co-receptor gene in Dendroctonus armandi leads to EAG response declining to major host volatiles

    PubMed Central

    Zhang, Ranran; Gao, Guanqun; Chen, Hui

    2016-01-01

    In this study, a polymerase chain reaction (PCR) based on homology genes of Orco was utilized to identify DarmOrco, which is essential for olfaction in D. armandi. The results showed that DarmOrco shares significant sequence homology with Orco proteins had known in other insects. Quantitative real-time PCR (qRT-PCR) analysis suggested that DarmOrco was abundantly expressed in adult D. armandi; by contrast, DarmOrco showed trace amounts of expression level in other stages. Of different tissues, DarmOrco expression level was the highest in the antennae. In order to understand the functional significance of Orco, we injected siRNA of DarmOrco into the conjunctivum between the second and third abdominal segments, and evaluated its expression after siRNA injected for 24 h, 48 h and 72 h. The results of qRT-PCR demonstrated that the reduction of mRNA expression level was significant (~80%) in DarmOrco siRNA-treated D. armandi than in water-injected and non-injected controls. The electroantennogram responses of females and males to 11 major volatiles of its host, were also reduced (30~68% for females; 16~70% for males) in siRNA-treated D. armandi compared with the controls. These results suggest that DarmOrco is crucial in mediating odorant perception. PMID:26979566

  20. Silencing of the olfactory co-receptor gene in Dendroctonus armandi leads to EAG response declining to major host volatiles.

    PubMed

    Zhang, Ranran; Gao, Guanqun; Chen, Hui

    2016-01-01

    In this study, a polymerase chain reaction (PCR) based on homology genes of Orco was utilized to identify DarmOrco, which is essential for olfaction in D. armandi. The results showed that DarmOrco shares significant sequence homology with Orco proteins had known in other insects. Quantitative real-time PCR (qRT-PCR) analysis suggested that DarmOrco was abundantly expressed in adult D. armandi; by contrast, DarmOrco showed trace amounts of expression level in other stages. Of different tissues, DarmOrco expression level was the highest in the antennae. In order to understand the functional significance of Orco, we injected siRNA of DarmOrco into the conjunctivum between the second and third abdominal segments, and evaluated its expression after siRNA injected for 24 h, 48 h and 72 h. The results of qRT-PCR demonstrated that the reduction of mRNA expression level was significant (~80%) in DarmOrco siRNA-treated D. armandi than in water-injected and non-injected controls. The electroantennogram responses of females and males to 11 major volatiles of its host, were also reduced (30~68% for females; 16~70% for males) in siRNA-treated D. armandi compared with the controls. These results suggest that DarmOrco is crucial in mediating odorant perception. PMID:26979566

  1. Responses of dune plant communities to continental uplift from a major earthquake: sudden releases from coastal squeeze.

    PubMed

    Rodil, Iván F; Jaramillo, Eduardo; Hubbard, David M; Dugan, Jenifer E; Melnick, Daniel; Velasquez, Carlos

    2015-01-01

    Vegetated dunes are recognized as important natural barriers that shelter inland ecosystems and coastlines suffering daily erosive impacts of the sea and extreme events, such as tsunamis. However, societal responses to erosion and shoreline retreat often result in man-made coastal defence structures that cover part of the intertidal and upper shore zones causing coastal squeeze and habitat loss, especially for upper shore biota, such as dune plants. Coseismic uplift of up to 2.0 m on the Peninsula de Arauco (South central Chile, ca. 37.5º S) caused by the 2010 Maule earthquake drastically modified the coastal landscape, including major increases in the width of uplifted beaches and the immediate conversion of mid to low sandy intertidal habitat to supralittoral sandy habitat above the reach of average tides and waves. To investigate the early stage responses in species richness, cover and across-shore distribution of the hitherto absent dune plants, we surveyed two formerly intertidal armoured sites and a nearby intertidal unarmoured site on a sandy beach located on the uplifted coast of Llico (Peninsula de Arauco) over two years. Almost 2 years after the 2010 earthquake, dune plants began to recruit, then rapidly grew and produced dune hummocks in the new upper beach habitats created by uplift at the three sites. Initial vegetation responses were very similar among sites. However, over the course of the study, the emerging vegetated dunes of the armoured sites suffered a slowdown in the development of the spatial distribution process, and remained impoverished in species richness and cover compared to the unarmoured site. Our results suggest that when released from the effects of coastal squeeze, vegetated dunes can recover without restoration actions. However, subsequent human activities and management of newly created beach and dune habitats can significantly alter the trajectory of vegetated dune development. Management that integrates the effects of natural

  2. Responses of Dune Plant Communities to Continental Uplift from a Major Earthquake: Sudden Releases from Coastal Squeeze

    PubMed Central

    Rodil, Iván F.; Jaramillo, Eduardo; Hubbard, David M.; Dugan, Jenifer E.; Melnick, Daniel; Velasquez, Carlos

    2015-01-01

    Vegetated dunes are recognized as important natural barriers that shelter inland ecosystems and coastlines suffering daily erosive impacts of the sea and extreme events, such as tsunamis. However, societal responses to erosion and shoreline retreat often result in man-made coastal defence structures that cover part of the intertidal and upper shore zones causing coastal squeeze and habitat loss, especially for upper shore biota, such as dune plants. Coseismic uplift of up to 2.0 m on the Peninsula de Arauco (South central Chile, ca. 37.5º S) caused by the 2010 Maule earthquake drastically modified the coastal landscape, including major increases in the width of uplifted beaches and the immediate conversion of mid to low sandy intertidal habitat to supralittoral sandy habitat above the reach of average tides and waves. To investigate the early stage responses in species richness, cover and across-shore distribution of the hitherto absent dune plants, we surveyed two formerly intertidal armoured sites and a nearby intertidal unarmoured site on a sandy beach located on the uplifted coast of Llico (Peninsula de Arauco) over two years. Almost 2 years after the 2010 earthquake, dune plants began to recruit, then rapidly grew and produced dune hummocks in the new upper beach habitats created by uplift at the three sites. Initial vegetation responses were very similar among sites. However, over the course of the study, the emerging vegetated dunes of the armoured sites suffered a slowdown in the development of the spatial distribution process, and remained impoverished in species richness and cover compared to the unarmoured site. Our results suggest that when released from the effects of coastal squeeze, vegetated dunes can recover without restoration actions. However, subsequent human activities and management of newly created beach and dune habitats can significantly alter the trajectory of vegetated dune development. Management that integrates the effects of natural

  3. Tissue-specific molecular immune response to lipopolysaccharide challenge in emaciated anadromous Arctic charr.

    PubMed

    Philip, Anju M; Jørgensen, Even H; Maule, Alec G; Vijayan, Mathilakath M

    2014-07-01

    Anadromous Arctic charr (Salvelinus alpinus) undergo voluntary winter fasting for months in the Arctic. We tested the hypothesis that extended fasting will compromise the ability of this species to evoke an immune response. Charr were either fed or fasted for 85 days and challenged with lipopolysaccharide (LPS), and the molecular immune response in the liver and spleen assessed at 8 and 96 h post-injection. LPS increased IL-1β, IL-8, and serum amyloid protein A (SAA) mRNA levels in both groups, but the liver IL-1β and IL-8, and spleen IL-8 responses were reduced in the fasted group. Fasting upregulated SOCS-1 and SOCS-2 mRNA abundance, while LPS stimulated SOCS-3 mRNA abundance and this response was higher in the fasted liver. Collectively, extended fasting and emaciation does not curtail the capacity of charr to evoke an immune response, whereas upregulation of SOCS may be a key adaptation to conserve energy by restricting the inflammatory response.

  4. Molecular response of Saccharomyces cerevisiae wine and laboratory strains to high sugar stress conditions.

    PubMed

    Jiménez-Martí, E; Zuzuarregui, A; Gomar-Alba, M; Gutiérrez, D; Gil, C; del Olmo, M

    2011-01-31

    One of the stress conditions that can affect Saccharomyces cerevisiae cells during their growth is osmotic stress. Under particular environments (for instance, during the production of alcoholic beverages) yeasts have to cope with osmotic stress caused by high sugar concentrations. Although the molecular changes and pathways involved in the response to saline or sorbitol stress are widely understood, less is known about how cells respond to high sugar concentrations. In this work we present a comprehensive study of the response to this form of stress which indicates important transcriptomic changes, especially in terms of the genes involved in both stress response and respiration, and the implication of the HOG pathway. We also describe several genes of an unknown function which are more highly expressed under 20% (w/v) glucose than under 2% (w/v) glucose. In this work we focus on the YHR087w (RTC3) gene and its encoded protein. Proteomic analysis of the mutant deletion strain reveals lower levels of several yeast Hsp proteins, which establishes a link between this protein and the response to several forms of stress. The relevance of YHR087W for the response to high sugar and other stress conditions and the relationship of the encoded protein with several Hsp proteins suggest applications of this gene in biotechnological processes in which response to stress is important.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27557767

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Molecular signals that shape the integrative responses of the heat-acclimated phenotype.

    PubMed

    Horowitz, Michal; Kodesh, Einat

    2010-12-01

    The introduction of molecular biology to thermoregulation was delayed compared with its application in other research fields pertinent to human health and disease. Using principles from molecular biology, we revisited fundamental problems in integrative and environmental physiology and were able to explore new research horizons. Global genomic responses in tandem with an appropriate physiological experimental model are a good experimental design strategy that can unravel the molecular mechanisms underlying integrative thermoregulatory responses. In this way, dynamic adaptation models, with accentuated or diminished regulatory circuits, triggered by superimposition of novel stressors sharing similar protective pathways, have significant benefits. On the basis of this approach, we will discuss the molecular physiological linkage of heat acclimation alone or combined with exercise training and decipher stress-specific genes in the thermoregulatory circuits in the heart and skeletal muscles. Opposing/competing adaptive features are required for each of the above-mentioned physiological conditions. Aerobic training increases the capacity to store/use ATP. In contrast, the acclimated phenotype attempts to counteract excessive heat production. Nevertheless, both treatments augment muscle force generation. These changes are tissue-specific; in the exercise-trained rat heart, there is up-regulation of Ca2+-induced Ca2+ release mechanism genes, whereas in the skeletal muscle (soleus), the enrichment is found in genes involved in metabolism. The final issue discussed in this review is the possibility that heat shock proteins serve as consensus markers of heat stress. The role of the autonomic nervous system in their induction during heat stress and how they affect integrative body systems are described.

  9. Molecular signals that shape the integrative responses of the heat-acclimated phenotype.

    PubMed

    Horowitz, Michal; Kodesh, Einat

    2010-12-01

    The introduction of molecular biology to thermoregulation was delayed compared with its application in other research fields pertinent to human health and disease. Using principles from molecular biology, we revisited fundamental problems in integrative and environmental physiology and were able to explore new research horizons. Global genomic responses in tandem with an appropriate physiological experimental model are a good experimental design strategy that can unravel the molecular mechanisms underlying integrative thermoregulatory responses. In this way, dynamic adaptation models, with accentuated or diminished regulatory circuits, triggered by superimposition of novel stressors sharing similar protective pathways, have significant benefits. On the basis of this approach, we will discuss the molecular physiological linkage of heat acclimation alone or combined with exercise training and decipher stress-specific genes in the thermoregulatory circuits in the heart and skeletal muscles. Opposing/competing adaptive features are required for each of the above-mentioned physiological conditions. Aerobic training increases the capacity to store/use ATP. In contrast, the acclimated phenotype attempts to counteract excessive heat production. Nevertheless, both treatments augment muscle force generation. These changes are tissue-specific; in the exercise-trained rat heart, there is up-regulation of Ca2+-induced Ca2+ release mechanism genes, whereas in the skeletal muscle (soleus), the enrichment is found in genes involved in metabolism. The final issue discussed in this review is the possibility that heat shock proteins serve as consensus markers of heat stress. The role of the autonomic nervous system in their induction during heat stress and how they affect integrative body systems are described. PMID:20404766

  10. Molecular characterization of Api g 1, the major allergen of celery (Apium graveolens), and its immunological and structural relationships to a group of 17-kDa tree pollen allergens.

    PubMed

    Breiteneder, H; Hoffmann-Sommergruber, K; O'Riordain, G; Susani, M; Ahorn, H; Ebner, C; Kraft, D; Scheiner, O

    1995-10-15

    Individuals suffering from immediate hypersensitivity (type-I allergy) to a particular pollen frequently display intolerance to several foods of plant origin. In this respect, individuals sensitized to birch pollen and/or mugwort pollen frequently display type-I allergic symptoms after ingestion of celery. In this study, we expressed the major allergenic protein of celery, Api g 1, which is responsible for the birch-celery syndrome, in the form of a non-fusion protein. The open reading frame of the cDNA of Api g 1 codes for a protein of 153 amino acids with a molecular mass of 16.2 kDa and 40% identity (60% similarity) to the major allergen of birch pollen, Bet v 1. Furthermore, Api g 1 exhibited similar characteristics to (a) two proteins in parsley induced by fungal infection, (b) the major tree pollen allergens and (c) pathogenesis-related and stress-induced proteins in other plant species. The reactivity of recombinant Api g 1 with IgE antibodies present in sera from celery intolerant patients was comparable to that of the natural celery allergen. Cross-reactivity with Bet v 1 was proven by cross-inhibition experiments, which provides further support for the existence of the birch-celery syndrome and for the suggestion that allergies to some vegetable foods are epiphenomena to allergies caused by inhalation of tree pollen.

  11. Profiling the physiological and molecular response to sulfonamidic drug in Procambarus clarkii.

    PubMed

    Nicosia, Aldo; Celi, Monica; Vazzana, Mirella; Damiano, Maria Alessandra; Parrinello, Nicolò; D'Agostino, Fabio; Avellone, Giuseppe; Indelicato, Serena; Mazzola, Salvatore; Cuttitta, Angela

    2014-11-01

    Sulfamethoxazole (SMZ) is one of the most widely employed sulfonamides. Because of the widespread use of SMZ, a considerable amount is indeed expected to be introduced into the environment. The cytotoxicity of SMZ relies mainly on arylhydroxylamine metabolites (S-NOH) of SMZ and it is associated with the production of reactive oxygen species (ROS). There is limited information about the toxic potential of SMZ at the cellular and molecular levels, especially in aquatic and/or non-target organisms. In the present study, the red swamp crayfish (Procambarus clarkii), being tolerant to extreme environmental conditions and resistant to disease, was used as a model organism to profile the molecular and physiological response to SMZ. Haemolymphatic-immunological parameters such as glucose serum levels and total haemocyte counts were altered; moreover, a significant increase in Hsp70 plasma levels was detected for the first time. Variations at the transcriptional level of proinflammatory genes (cyclooxygenase-1, COX 1, and cyclooxygenase-2, COX 2), antioxidant enzymes (glutathione-S-transferase, GST and manganese superoxide dismutase MnSOD), stress response and Fenton reaction inhibitor genes (heat-shock protein 70 HSP70, metallothionein, MT and ferritin, FT) were evaluated, and alterations in the canonical gene expression patterns emerged. Considering these results, specific mechanisms involved in maintaining physiological homeostasis and adaptation in response to perturbations are suggested.

  12. First molecular identification and report of genetic diversity of Strongyloides stercoralis, a current major soil-transmitted helminth in humans from Lao People's Democratic Republic.

    PubMed

    Laymanivong, Sakhone; Hangvanthong, Bouasy; Insisiengmay, Bounnaloth; Vanisaveth, Viengxay; Laxachack, Pinnakhone; Jongthawin, Jurairat; Sanpool, Oranuch; Thanchomnang, Tongjit; Sadaow, Lakkhana; Phosuk, Issarapong; Rodpai, Rutchanee; Maleewong, Wanchai; Intapan, Pewpan M

    2016-08-01

    Strongyloidiasis is a major soil-transmitted helminth (STH) disease that affects people worldwide. We present updated data on prevalence in the Lao People's Democratic Republic (Lao PDR) in 2015, arising from a community cross-sectional helminthiasis survey. Fecal samples were collected from 327 individuals across three provinces in Lao PDR (Luang Prabang in the north, Khammouane in the center, and Champasack in the south). Agar plate culture and Kato-Katz methods were used to examine duplicate stool samples from each participant to detect Strongyloides stercoralis and co-infecting helminths. Overall prevalences of S. strercoralis human hookworm, Taenia spp., Trichuris trichiura, Ascaris lumbricoides, and Enterobius vermicularis were 41.0, 28.1, 4.9, 4.0, 1.5, and 0.9 %, respectively. The prevalence of miscellaneous trematodiases (including opisthorchiasis) was 37.9 % and of Schistosoma mekongi infection was 0.3 %. Strongyloidiasis is a current major STH disease in Lao PDR. We also report the molecular-phylogenetic identification of S. stercoralis adult males collected from 40 representative human strongyliodiasis fecal samples. DNA was extracted, amplified, and sequenced from a portion of the mitochondrial cox1 gene and the nuclear 18S ribosomal DNA. Phylogenetic analyses indicated that all specimens sequenced belonged to S. stercoralis (Bavay, 1876) Stiles and Hassall, 1902. The cox1 sequences exhibited great diversity (24 haplotypes) in Lao PDR. This is the first molecular identification and report of genetic diversity of S. stercoralis in humans from Lao PDR. An effective parasite control program is needed to reduce the serious health impacts. PMID:27083185

  13. The anion-binding polyanion: a molecular cobalt vanadium oxide with anion-sensitive visual response.

    PubMed

    Seliverstov, Andrey; Forster, Johannes; Heiland, Magdalena; Unfried, Johannes; Streb, Carsten

    2014-07-25

    An anionic molecular cobalt vanadium oxide cluster, (n-Bu4N)3[Co(AcO)V4O12] and its use as anion binding site is reported. Cluster formation is controlled by an anion-dependent dynamic solution equilibrium. Reversible anion binding in solution leads to significant spectral changes, allowing the ratiometric optical detection of the anion concentration in situ, even under harsh thermal conditions (T = 90 °C). Comparative studies showed that the spectral response is dependent on the type of anion so that carboxylates, weakly coordinating anions and halides can be distinguished.

  14. Cellular and molecular responses of Neurospora crassa to non-thermal plasma at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Park, Gyungsoon; Ryu, Young H.; Hong, Young J.; Choi, Eun H.; Uhm, Han S.

    2012-02-01

    Filamentous fungi have been rarely explored in terms of plasma treatments. This letter presents the cellular and molecular responses of the filamentous fungus Neurospora crassa to an argon plasma jet at atmospheric pressure. The viability and cell morphology of N. crassa spores exposed to plasma were both significantly reduced depending on the exposure time when treated in water. The intracellular genomic DNA content was dramatically reduced in fungal tissues after a plasma treatment and the transcription factor tah-3 was found to be required for fungal tolerance to a harsh plasma environment.

  15. Leukemic stem cell persistence in chronic myeloid leukemia patients in deep molecular response induced by tyrosine kinase inhibitors and the impact of therapy discontinuation.

    PubMed

    Chomel, Jean Claude; Bonnet, Marie-Laure; Sorel, Nathalie; Sloma, Ivan; Bennaceur-Griscelli, Annelise; Rea, Delphine; Legros, Laurence; Marfaing-Koka, Anne; Bourhis, Jean-Henri; Ame, Shanti; Guerci-Bresler, Agnès; Rousselot, Philippe; Turhan, Ali G

    2016-06-01

    During the last decade, the use of tyrosine kinase inhibitor (TKI) therapy has modified the natural history of chronic myeloid leukemia (CML) allowing an increase of the overall and disease-free survival, especially in patients in whom molecular residual disease becomes undetectable. However, it has been demonstrated that BCR-ABL1- expressing leukemic stem cells (LSCs) persist in patients in deep molecular response. It has also been shown that the discontinuation of Imatinib leads to a molecular relapse in the majority of cases. To determine a possible relationship between these two phenomena, we have evaluated by clonogenic and long-term culture initiating cell (LTC-IC) assays, the presence of BCR-ABL1-expressing LSCs in marrow samples from 21 patients in deep molecular response for three years after TKI therapy (mean duration seven years). LSCs were detected in 4/21 patients. Discontinuation of TKI therapy in 13/21 patients led to a rapid molecular relapse in five patients (4 without detectable LSCs and one with detectable LSCs). No relapse occurred in the eight patients still on TKI therapy, whether LSCs were detectable or not. Thus, this study demonstrates for the first time the in vivo efficiency of TKIs, both in the progenitor and the LSC compartments. It also confirms the persistence of leukemic stem cells in patients in deep molecular response, certainly at the origin of relapses. Finally, it emphasizes the difficulty of detecting residual LSCs due to their rarity and their low BCR-ABL1 mRNA expression. PMID:27167108

  16. Leukemic stem cell persistence in chronic myeloid leukemia patients in deep molecular response induced by tyrosine kinase inhibitors and the impact of therapy discontinuation

    PubMed Central

    Chomel, Jean Claude; Bonnet, Marie Laure; Sorel, Nathalie; Sloma, Ivan; Bennaceur-Griscelli, Annelise; Rea, Delphine; Legros, Laurence; Marfaing-Koka, Anne; Bourhis, Jean-Henri; Ame, Shanti; Guerci-Bresler, Agnès; Rousselot, Philippe; Turhan, Ali G.

    2016-01-01

    During the last decade, the use of tyrosine kinase inhibitor (TKI) therapy has modified the natural history of chronic myeloid leukemia (CML) allowing an increase of the overall and disease-free survival, especially in patients in whom molecular residual disease becomes undetectable. However, it has been demonstrated that BCR-ABL1- expressing leukemic stem cells (LSCs) persist in patients in deep molecular response. It has also been shown that the discontinuation of Imatinib leads to a molecular relapse in the majority of cases. To determine a possible relationship between these two phenomena, we have evaluated by clonogenic and long-term culture initiating cell (LTC-IC) assays, the presence of BCR-ABL1-expressing LSCs in marrow samples from 21 patients in deep molecular response for three years after TKI therapy (mean duration seven years). LSCs were detected in 4/21 patients. Discontinuation of TKI therapy in 13/21 patients led to a rapid molecular relapse in five patients (4 without detectable LSCs and one with detectable LSCs). No relapse occurred in the eight patients still on TKI therapy, whether LSCs were detectable or not. Thus, this study demonstrates for the first time the in vivo efficiency of TKIs, both in the progenitor and the LSC compartments. It also confirms the persistence of leukemic stem cells in patients in deep molecular response, certainly at the origin of relapses. Finally, it emphasizes the difficulty of detecting residual LSCs due to their rarity and their low BCR-ABL1 mRNA expression. PMID:27167108

  17. Specific glucose-to-SPR signal transduction at physiological pH by molecularly imprinted responsive hybrid microgels.

    PubMed

    Wu, Weitai; Shen, Jing; Li, Yaoxin; Zhu, Hongbo; Banerjee, Probal; Zhou, Shuiqin

    2012-10-01

    We design a class of imprinted hybrid microgels that can optically monitor glucose levels with high sensitivity and selectivity in complex media at physiological pH, acting like a "glucose-indicator". Such imprinted hybrid microgels were made of Ag nanoparticles (NPs) in situ immobilized in molecularly imprinted glucose-responsive polymeric microgel templates containing phenylboronic acids in such a way that the Ag NPs were confined in the immediate vicinity to each other, thus enabling their efficient plasmon coupling. The glucose-responsive gel-actuated tunable plasmon coupling effects among the Ag NPs immobilized inside the microgels were investigated in both phosphate buffer solution and artificial tear fluid. The visually evident color shift from yellow to red of the hybrid microgel dispersion in response to a glucose concentration change from 0 to 20.0 mm allows one to see the glucose levels without instrumental aid. The surface plasmon resonance (SPR) response of the imprinted hybrid microgels at appropriate loading amount of Ag NPs is free of the significant interferences from the major non-glucose constituents, enabling the optical glucose sensing in artificial tear fluids with the achieved root-mean-squared error of predication (RMSEC) as low as 13.7 μM (~0.2 mg/dL) over a clinically relevant glucose concentration range of 0.1-20 mm (1.8-360 mg/dL). The highly versatile imprinted hybrid microgels could potentially be used for continuous glucose monitoring in clinical diagnostic and bioprocess applications. PMID:22800540

  18. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

    PubMed Central

    Giannattasio, Sergio; Guaragnella, Nicoletta; Ždralević, Maša; Marra, Ersilia

    2013-01-01

    Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications. PMID:23430312

  19. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid.

    PubMed

    Giannattasio, Sergio; Guaragnella, Nicoletta; Zdralević, Maša; Marra, Ersilia

    2013-01-01

    Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications. PMID:23430312

  20. Parametric hierarchical matrix approach for the wideband optical response of large-scale molecular aggregates

    NASA Astrophysics Data System (ADS)

    Ansari-Oghol-Beig, Davood; Rostami, Masoud; Chernobrovkina, Ekaterina; Saikin, Semion K.; Valleau, Stéphanie; Mosallaei, Hossein; Aspuru-Guzik, Alán

    2013-10-01

    Fast and efficient calculations of optical responses using electromagnetic models require computational acceleration and compression techniques. A hierarchical matrix approach is adopted for this purpose. In order to model large-scale molecular structures, these methods should be applied over wide frequency spectra. Here, we introduce a novel parametric hierarchical matrix method that allows one for a rapid construction of a wideband system representation and enables an efficient wideband solution. We apply the developed method to the modeling of the optical response of bacteriochlorophyll tubular aggregates as found in green photosynthetic bacteria. We show that the parametric method can provide one with the frequency and time-domain solutions for structures of the size of 100 000 molecules, which is comparable to the size of the whole antenna complex in a bacterium. The absorption spectrum is calculated and the significance of electrodynamic retardation effects for relatively large structures, i.e., with respect to the wavelength of light, is briefly studied.

  1. Molecular characterization and biological response to respiration inhibitors of Pyricularia isolates from ctenanthe and rice plants.

    PubMed

    Paplomatas, Epaminondas J; Pappas, Athanasios C; Syranidou, Elene

    2005-07-01

    The molecular profile and the biological response of isolates of Pyricularia oryzae Cavara obtained from ctenanthe to two strobilurins (azoxystrobin, kresoxim-methyl) and the phenylpyridinamine fungicide fluazinam were characterized, and compared with isolates from rice plants. Five different isozymes (alpha-esterase, lactate, malate, isocitrate and sorbitol dehydrogenases) and five random decamer primers for RAPD-PCR were used to generate molecular markers. Using unweighted pair-group with arithmetic average analysis, ctenanthe isolates were found to form a separate group distinct from that of the rice isolates for both sets of markers. Amplified polymorphic sequences of mitochondrial cytochrome b that were digested with Fnu4HI or StyI revealed no differences among Pyricularia isolates at amino acid positions 143 or 129 which confer resistance to strobilurins in several fungi. In absence of the alternative respiration inhibitor salicylhydroxamic acid (SHAM) the three fungicides showed inferior and variable efficacy, with a trend toward the rice isolate being less sensitive. The addition of SHAM enhanced the effectiveness of all fungicides against isolates regardless of their origin. Appressorium formation was the most vulnerable target of action of the respiration inhibitors and azoxystrobin the most effective. This is the first report of a comparison between the molecular profiles and sensitivities to respiration inhibitors for Pyricularia oryzae isolates from a non-gramineous host and from rice. PMID:15739234

  2. Molecular characterization and biological response to respiration inhibitors of Pyricularia isolates from ctenanthe and rice plants.

    PubMed

    Paplomatas, Epaminondas J; Pappas, Athanasios C; Syranidou, Elene

    2005-07-01

    The molecular profile and the biological response of isolates of Pyricularia oryzae Cavara obtained from ctenanthe to two strobilurins (azoxystrobin, kresoxim-methyl) and the phenylpyridinamine fungicide fluazinam were characterized, and compared with isolates from rice plants. Five different isozymes (alpha-esterase, lactate, malate, isocitrate and sorbitol dehydrogenases) and five random decamer primers for RAPD-PCR were used to generate molecular markers. Using unweighted pair-group with arithmetic average analysis, ctenanthe isolates were found to form a separate group distinct from that of the rice isolates for both sets of markers. Amplified polymorphic sequences of mitochondrial cytochrome b that were digested with Fnu4HI or StyI revealed no differences among Pyricularia isolates at amino acid positions 143 or 129 which confer resistance to strobilurins in several fungi. In absence of the alternative respiration inhibitor salicylhydroxamic acid (SHAM) the three fungicides showed inferior and variable efficacy, with a trend toward the rice isolate being less sensitive. The addition of SHAM enhanced the effectiveness of all fungicides against isolates regardless of their origin. Appressorium formation was the most vulnerable target of action of the respiration inhibitors and azoxystrobin the most effective. This is the first report of a comparison between the molecular profiles and sensitivities to respiration inhibitors for Pyricularia oryzae isolates from a non-gramineous host and from rice.

  3. Hydration patterns of graphene-based nanomaterials (GBNMs) play a major role in the stability of a helical protein: a molecular dynamics simulation study.

    PubMed

    Baweja, Lokesh; Balamurugan, Kanagasabai; Subramanian, Venkatesan; Dhawan, Alok

    2013-11-19

    Graphene-based nanomaterials (GBNMs) [graphene oxide (GO), reduced graphene oxide (rGO), and graphene] have been recognized as potential candidates for various biomedical applications ranging from biosensing platform to cellular delivery of proteins and peptides. However, GBNMs induced conformational changes in proteins are the major concerns in realizing their full potential in aforementioned applications. Despite several studies, the effect of GBNMs on the conformation of proteins is still not well understood. Therefore, an attempt was made to investigate the effect of GBNMs on the adsorption and conformation of positively charged cytoplasmic protein using molecular dynamics (MD) simulations. Our study showed that the adsorption of protein on GO was highly selective and mediated through electrostatic interactions (hydrogen bond/salt bridge interactions), whereas the van der Waals and π-π stacking interactions were the major driving forces for the adsorption of protein on rGO and graphene. The secondary structure analysis showed the conformational stability of the protein on GO may be attributed to the extensive hydration of GO surface and the absence of tyrosine residues in π-π stacking with π regions of GO. The GO surface acts as a hydrogen bond acceptor similar to the protein's natural receptor present in a physiological environment. This computational study has also explored the artificial protein receptor like potential of GO.

  4. Formation of high-molecular-weight angiotensinogen during pregnancy is a result of competing redox reactions with the proform of eosinophil major basic protein.

    PubMed

    Kløverpris, Søren; Skov, Louise L; Glerup, Simon; Pihl, Kasper; Christiansen, Michael; Oxvig, Claus

    2013-01-01

    The plasma concentration of the placentally derived proMBP (proform of eosinophil major basic protein) increases in pregnancy, and three different complexes containing proMBP have been isolated from pregnancy plasma and serum: a 2:2 complex with the metalloproteinase, PAPP-A (pregnancy-associated plasma protein-A), a 2:2 complex with AGT (angiotensinogen) and a 2:2:2 complex with AGT and complement C3dg. In the present study we show that during human pregnancy, all of the circulating proMBP exists in covalent complexes, bound to either PAPP-A or AGT. We also show that the proMBP-AGT complex constitutes the major fraction of circulating HMW (high-molecular weight) AGT in late pregnancy, and that this complex is able to further associate with complement C3 derivatives post-sampling. Clearance experiments in mice suggest that complement C3-based complexes are removed faster from the circulation compared to monomeric AGT and the proMBP-AGT complex. Furthermore, we have used recombinant proteins to analyse the formation of the proMBP-PAPP-A and the proMBP-AGT complexes, and we demonstrate that they are competing reactions, depending on the same cysteine residue of proMBP, but differentially on the redox potential, potentially important for the relative amounts of the complexes in vivo. These findings may be important physiologically, since the biochemical properties of the proteins change as a consequence of complex formation.

  5. Molecular Adaptation Mechanisms Employed by Ethanologenic Bacteria in Response to Lignocellulose-derived Inhibitory Compounds

    PubMed Central

    Ibraheem, Omodele; Ndimba, Bongani K.

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

  6. Molecular adaptation mechanisms employed by ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds.

    PubMed

    Ibraheem, Omodele; Ndimba, Bongani K

    2013-01-01

    Current international interest in finding alternative sources of energy to the diminishing supplies of fossil fuels has encouraged research efforts in improving biofuel production technologies. In countries which lack sufficient food, the use of sustainable lignocellulosic feedstocks, for the production of bioethanol, is an attractive option. In the pre-treatment of lignocellulosic feedstocks for ethanol production, various chemicals and/or enzymatic processes are employed. These methods generally result in a range of fermentable sugars, which are subjected to microbial fermentation and distillation to produce bioethanol. However, these methods also produce compounds that are inhibitory to the microbial fermentation process. These compounds include products of sugar dehydration and lignin depolymerisation, such as organic acids, derivatised furaldehydes and phenolic acids. These compounds are known to have a severe negative impact on the ethanologenic microorganisms involved in the fermentation process by compromising the integrity of their cell membranes, inhibiting essential enzymes and negatively interact with their DNA/RNA. It is therefore important to understand the molecular mechanisms of these inhibitions, and the mechanisms by which these microorganisms show increased adaptation to such inhibitors. Presented here is a concise overview of the molecular adaptation mechanisms of ethanologenic bacteria in response to lignocellulose-derived inhibitory compounds. These include general stress response and tolerance mechanisms, which are typically those that maintain intracellular pH homeostasis and cell membrane integrity, activation/regulation of global stress responses and inhibitor substrate-specific degradation pathways. We anticipate that understanding these adaptation responses will be essential in the design of 'intelligent' metabolic engineering strategies for the generation of hyper-tolerant fermentation bacteria strains. PMID:23847442

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

    PubMed Central

    Hann, Claire T.; Bequette, Carlton J.; Dombrowski, James E.; Stratmann, Johannes W.

    2014-01-01

    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. Molecular mechanisms that explain how methanol affects plant defenses are poorly understood. Here we show that exogenously supplied methanol alone has weak effects on defense signaling in three dicot species, however, it profoundly alters signaling responses to danger- and microbe-associated molecular patterns (DAMPs, MAMPs) such as the alarm hormone systemin, the bacterial flagellum-derived flg22 peptide, and the fungal cell wall-derived oligosaccharide chitosan. In the presence of methanol the kinetics and amplitudes of DAMP/MAMP-induced MAP kinase (MAPK) activity and oxidative burst are altered in tobacco and tomato suspension-cultured cells, in Arabidopsis seedlings and tomato leaf tissue. As a possible consequence of altered DAMP/MAMP signaling, methanol suppressed the expression of the defense genes PR-1 and PI-1 in tomato. In cell cultures of the grass tall fescue (Festuca arundinacea, Poaceae, Monocots), methanol alone activates MAPKs and increases chitosan-induced MAPK activity, and in the darnel grass Lolium temulentum (Poaceae), it alters wound-induced MAPK signaling. We propose that methanol can be recognized by plants as a sign of the damaged self. In dicots, methanol functions as a DAMP-like alarm signal with little elicitor activity on its own, whereas it appears to function as an elicitor-active DAMP in monocot grasses. Ethanol had been implicated in plant stress responses, although the source of ethanol in plants is not well established. We found that it has a similar effect as methanol on responses to MAMPs and DAMPs. PMID:25360141

  8. Molecular mechanisms responsible for interaction or differentiation between hydrotropism and gravitropism in roots

    NASA Astrophysics Data System (ADS)

    Takahashi, Hideyuki; Morohashi, Keita; Kobayashi, Akie; Miyazawa, Yutaka; Fujii, Nobuharu

    Roots display hydrotropism in response to moisture gradient, but it is often interfered by gravitropic response on Earth. We demonstrated that roots of cucumber seedlings showed positive hydrotropism when exposed to moisture gradient and rotated on a two-axis clinostat. Under stationary conditions, however, gravitropic response overcame hydrotropic response. Using this experimental system, we examined the role of auxin in hydrotropism. Cucumber roots showed severely reduced hydrotropic response when treated with inhibitors of auxin transport (efflux) or auxin action. mRNA accumulation of auxin-inducible gene, CsIAA1, became more abundant in the concave side of the hydrotropically responding roots, compared with that of the convex side. To understand the auxin dynamics in cucumber roots, we isolated cDNAs of auxin efflux carriers, CsPINs, and examined the localization of their mRNAs and proteins. Of these CsPINs, CsPIN5 was localized peripherally in the region between lateral root cap and elongation zone of cucumber roots. In hydrotropically responding roots, CsPIN5 proteins decreased in the convex side while it was maintained in the concave side. These results suggest that auxin dynamics and action play important roles in inducing hydrotropism, similarly to the case of gravitropism in roots. In cucumber roots, therefore, hydrotropism interacts with gravitropism, possibly by competitive manner in auxin dynamics. We are currently preparing spaceflight experiment for separating the hydrotropic response mechanism from that of gravitropism to understand the regulatory mechanisms of root growth orientation and determine whether hydrotropic response can be used for controlling growth orientation of roots in microgravity. On the other hand, we identified MIZ1 gene essential for hydrotropism but not gravitropism in Arabidopsis roots. Thus, there exist molecular mechanisms shared and differed in the two tropisms.

  9. Assessment at 6 months may be warranted for patients with chronic myeloid leukemia with no major cytogenetic response at 3 months

    PubMed Central

    Nazha, Aziz; Kantarjian, Hagop; Jain, Preetesh; Romo, Carlos; Jabbour, Elias; Quintas-Cardama, Alfonso; Luthra, Raja; Abruzzo, Lynne; Borthakur, Gautam; Ravandi, Farhad; Pierce, Sherry; O’Brien, Susan; Cortes, Jorge

    2013-01-01

    Response to tyrosine kinase inhibitors at three months is a predictor for long-term outcome in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. We analyzed 456 newly diagnosed chronic myeloid leukemia patients treated with tyrosine kinase inhibitors to determine their outcome based on their response at six months. Forty-four (10%) patients did not achieve major cytogenetic response at three months: 18 of 67 (27%) patients treated with imatinib 400; 18 of 196 (9%) with imatinib 800; and 8 of 193 (4%) with 2nd generation tyrosine kinase inhibitors. Among them, 19 (43%) achieved major cytogenetic response at six months and subsequently had an overall outcome similar to the patients who achieved a major cytogenetic response at three months. In conclusion, the response to tyrosine kinase inhibitors at three months is a static, one-time measure. Assessing the response at six months of patients with poor response at three months may provide a better predictor for long-term outcome. PMID:23812943

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

    PubMed

    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

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

    Introduction 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. Materials and Methods 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. Results 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%). Conclusions 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. PMID:27171373

  13. Thermo-responsive behavior of borinic acid polymers: experimental and molecular dynamics studies.

    PubMed

    Wan, Wen-Ming; Zhou, Peng; Cheng, Fei; Sun, Xiao-Li; Lv, Xin-Hu; Li, Kang-Kang; Xu, Hai; Sun, Miao; Jäkle, Frieder

    2015-09-28

    The thermo-responsive properties of borinic acid polymers were investigated by experimental and molecular dynamics simulation studies. The homopolymer poly(styrylphenyl(tri-iso-propylphenyl)borinic acid) (PBA) exhibits an upper critical solution temperature (UCST) in polar organic solvents that is tunable over a wide temperature range by addition of small amounts of H2O. The UCST of a 1 mg mL(-1) PBA solution in DMSO can be adjusted from 20 to 100 °C by varying the H2O content from ∼0-2.5%, in DMF from 0 to 100 °C (∼3-17% H2O content), and in THF from 0 to 60 °C (∼4-19% H2O). The UCST increases almost linearly from the freezing point of the solvent with higher freezing point to the boiling point of the solvent with the lower boiling point. The mechanistic aspects of this process were investigated by molecular dynamics simulations. The latter indicate rapid and strong hydrogen-bond formation between BOH moieties and H2O molecules, which serve as crosslinkers to form an insoluble network. Our results suggest that borinic acid-containing polymers are promising as new "smart" materials, which display thermo-responsive properties that are tunable over a wide temperature range.

  14. Thermo-responsive behavior of borinic acid polymers: experimental and molecular dynamics studies.

    PubMed

    Wan, Wen-Ming; Zhou, Peng; Cheng, Fei; Sun, Xiao-Li; Lv, Xin-Hu; Li, Kang-Kang; Xu, Hai; Sun, Miao; Jäkle, Frieder

    2015-09-28

    The thermo-responsive properties of borinic acid polymers were investigated by experimental and molecular dynamics simulation studies. The homopolymer poly(styrylphenyl(tri-iso-propylphenyl)borinic acid) (PBA) exhibits an upper critical solution temperature (UCST) in polar organic solvents that is tunable over a wide temperature range by addition of small amounts of H2O. The UCST of a 1 mg mL(-1) PBA solution in DMSO can be adjusted from 20 to 100 °C by varying the H2O content from ∼0-2.5%, in DMF from 0 to 100 °C (∼3-17% H2O content), and in THF from 0 to 60 °C (∼4-19% H2O). The UCST increases almost linearly from the freezing point of the solvent with higher freezing point to the boiling point of the solvent with the lower boiling point. The mechanistic aspects of this process were investigated by molecular dynamics simulations. The latter indicate rapid and strong hydrogen-bond formation between BOH moieties and H2O molecules, which serve as crosslinkers to form an insoluble network. Our results suggest that borinic acid-containing polymers are promising as new "smart" materials, which display thermo-responsive properties that are tunable over a wide temperature range. PMID:26256052

  15. Molecular Mechanism for Cellular Response to β-Escin and Its Therapeutic Implications

    PubMed Central

    Perzanowska, Anna; Dutkiewicz, Malgorzata; Kowalewska, Magdalena; Grabowska, Iwona; Maciejko, Dorota; Fogtman, Anna; Dadlez, Michal; Koziak, Katarzyna

    2016-01-01

    β-escin is a mixture of triterpene saponins isolated from the horse chestnut seeds (Aesculus hippocastanum L.). The anti-edematous, anti-inflammatory and venotonic properties of β-escin have been the most extensively clinically investigated effects of this plant-based drug and randomized controlled trials have proved the efficacy of β-escin for the treatment of chronic venous insufficiency. However, despite the clinical recognition of the drug its pharmacological mechanism of action still remains largely elusive. To determine the cellular and molecular basis for the therapeutic effectiveness of β-escin we performed discovery and targeted proteomic analyses and in vitro evaluation of cellular and molecular responses in human endothelial cells under inflammatory conditions. Our results demonstrate that in endothelial cells β-escin potently induces cholesterol synthesis which is rapidly followed with marked fall in actin cytoskeleton integrity. The concomitant changes in cell functioning result in a significantly diminished responses to TNF-α stimulation. These include reduced migration, alleviated endothelial monolayer permeability, and inhibition of NFκB signal transduction leading to down-expression of TNF-α—induced effector proteins. Moreover, the study provides evidence for novel therapeutic potential of β-escin beyond the current vascular indications. PMID:27727329

  16. Molecular origins of higher harmonics in large-amplitude oscillatory shear flow: Shear stress response

    NASA Astrophysics Data System (ADS)

    Gilbert, P. H.; Giacomin, A. J.

    2016-10-01

    Recent work has focused on deepening our understanding of the molecular origins of the higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. For instance, these higher harmonics have been explained by just considering the orientation distribution of rigid dumbbells suspended in a Newtonian solvent. These dumbbells, when in dilute suspension, form the simplest relevant molecular model of polymer viscoelasticity, and this model specifically neglects interactions between the polymer molecules [R. B. Bird et al., "Dilute rigid dumbbell suspensions in large-amplitude oscillatory shear flow: Shear stress response," J. Chem. Phys. 140, 074904 (2014)]. In this paper, we explore these interactions by examining the Curtiss-Bird model, a kinetic molecular theory designed specifically to account for the restricted motions that arise when polymer chains are concentrated, thus interacting and specifically, entangled. We begin our comparison using a heretofore ignored explicit analytical solution [X.-J. Fan and R. B. Bird, "A kinetic theory for polymer melts. VI. Calculation of additional material functions," J. Non-Newtonian Fluid Mech. 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ = 0 corresponds to reptation, ɛ > 1/8 to rod-climbing, 1/5 ≤ ɛ ≤ 3/4 to reasonable predictions for shear-thinning in steady simple shear flow, and ɛ = 1 to the dilute solution without hydrodynamic interaction. In this paper, we examine the shapes of the shear stress versus shear rate loops for the special cases ɛ = (" separators=" 0 , 1 / 8 , 3 / 8 , 1 ) , and we compare these with those of rigid dumbbell and reptation model predictions.

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

    SciTech Connect

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

    1988-06-01

    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.

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

    PubMed Central

    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

  19. Brassinosteroids modulate the efficiency of plant immune responses to microbe-associated molecular patterns.

    PubMed

    Belkhadir, Youssef; Jaillais, Yvon; Epple, Petra; Balsemão-Pires, Emilia; Dangl, Jeffery L; Chory, Joanne

    2012-01-01

    Metazoans and plants use pattern recognition receptors (PRRs) to sense conserved microbial-associated molecular patterns (MAMPs) in the extracellular environment. In plants, the bacterial MAMPs flagellin and elongation factor Tu (EF-Tu) activate distinct, phylogenetically related cell surface pattern recognition receptors of the leucine-rich repeat receptor kinase (LRR-RK) family called FLS2 and EF-Tu receptor, respectively. BAK1 is an LRR-RK coreceptor for both FLS2 and EF-Tu receptor. BAK1 is also a coreceptor for the plant brassinosteroid (BR) receptor, the LRR-RK BRI1. Binding of BR to BRI1 primarily promotes cell elongation. Here, we tune the BR pathway response to establish how plant cells can generate functionally different cellular outputs in response to MAMPs and pathogens. We demonstrate that BR can act antagonistically or synergistically with responses to MAMPs. We further show that the synergistic activities of BRs on MAMP responses require BAK1. Our results highlight the importance of plant steroid homeostasis as a critical step in the establishment of plant immunity. We propose that tradeoffs associated with plasticity in the face of infection are layered atop plant steroid developmental programs.

  20. Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin.

    PubMed

    Chang, Jordan; Lu, Yuan; Boswell, William T; Boswell, Mikki; Caballero, Kaela L; Walter, Ronald B

    2015-12-01

    Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure have been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of different parental species and for interspecies hybrids produced from crossing them. Additionally, it has been shown that exposure to "cool white" fluorescent light induces a shift in the genetic profiles of Xiphophorus skin that is nearly as robust as the UVB response, but involves a fundamentally different set of genes. Given these results and the use of Xiphophorus interspecies hybrids as an experimental model for UVB inducible melanoma, it is of interest to characterize genes that may be transcriptionally modulated in a wavelength specific manner. The global molecular genetic response of skin upon exposure of the intact animal to specific wavelengths of light has not been investigated. Herein, we report results of RNA-Seq experiments from the skin of male Xiphophorus maculatus Jp 163 B following exposure to varied 50nm wavelengths of light ranging from 300-600nm. We identify two specific wavelength regions, 350-400nm (88 genes) and 500-550nm (276 genes), that exhibit transcriptional modulation of a significantly greater number of transcripts than any of the other 50nm regions in the 300-600nm range. Observed functional sets of genes modulated within these two transcriptionally active light regions suggest different mechanisms of gene modulation.

  1. Functional dissection of a strong and specific microbe-associated molecular pattern-responsive synthetic promoter.

    PubMed

    Lehmeyer, Mona; Kanofsky, Konstantin; Hanko, Erik K R; Ahrendt, Sarah; Wehrs, Maren; Machens, Fabian; Hehl, Reinhard

    2016-01-01

    Synthetic promoters are important for temporal and spatial gene expression in transgenic plants. To identify novel microbe-associated molecular pattern (MAMP)-responsive cis-regulatory sequences for synthetic promoter design, a combination of bioinformatics and experimental approaches was employed. One cis-sequence was identified which confers strong MAMP-responsive reporter gene activity with low background activity. The 35-bp-long cis-sequence was identified in the promoter of the Arabidopsis thaliana DJ1E gene, a homologue of the human oncogene DJ1. In this study, this cis-sequence is shown to be a tripartite cis-regulatory module (CRM). A synthetic promoter with four copies of the CRM linked to a minimal promoter increases MAMP-responsive reporter gene expression compared to the wild-type DJ1E promoter. The CRM consists of two WT-boxes (GGACTTTT and GGACTTTG) and a variant of the GCC-box (GCCACC), all required for MAMP and salicylic acid (SA) responsivity. Yeast one-hybrid screenings using a transcription factor (TF)-only prey library identified two AP2/ERFs, ORA59 and ERF10, interacting antagonistically with the CRM. ORA59 activates reporter gene activity and requires the consensus core sequence GCCNCC for gene expression activation. ERF10 down-regulates MAMP-responsive gene expression. No TFs interacting with the WT-boxes GGACTTTT and GGACTTTG were selected in yeast one-hybrid screenings with the TF-only prey library. In transgenic Arabidopsis, the synthetic promoter confers strong and specific reporter gene activity in response to biotrophs and necrotrophs as well as SA.

  2. Functional dissection of a strong and specific microbe-associated molecular pattern-responsive synthetic promoter.

    PubMed

    Lehmeyer, Mona; Kanofsky, Konstantin; Hanko, Erik K R; Ahrendt, Sarah; Wehrs, Maren; Machens, Fabian; Hehl, Reinhard

    2016-01-01

    Synthetic promoters are important for temporal and spatial gene expression in transgenic plants. To identify novel microbe-associated molecular pattern (MAMP)-responsive cis-regulatory sequences for synthetic promoter design, a combination of bioinformatics and experimental approaches was employed. One cis-sequence was identified which confers strong MAMP-responsive reporter gene activity with low background activity. The 35-bp-long cis-sequence was identified in the promoter of the Arabidopsis thaliana DJ1E gene, a homologue of the human oncogene DJ1. In this study, this cis-sequence is shown to be a tripartite cis-regulatory module (CRM). A synthetic promoter with four copies of the CRM linked to a minimal promoter increases MAMP-responsive reporter gene expression compared to the wild-type DJ1E promoter. The CRM consists of two WT-boxes (GGACTTTT and GGACTTTG) and a variant of the GCC-box (GCCACC), all required for MAMP and salicylic acid (SA) responsivity. Yeast one-hybrid screenings using a transcription factor (TF)-only prey library identified two AP2/ERFs, ORA59 and ERF10, interacting antagonistically with the CRM. ORA59 activates reporter gene activity and requires the consensus core sequence GCCNCC for gene expression activation. ERF10 down-regulates MAMP-responsive gene expression. No TFs interacting with the WT-boxes GGACTTTT and GGACTTTG were selected in yeast one-hybrid screenings with the TF-only prey library. In transgenic Arabidopsis, the synthetic promoter confers strong and specific reporter gene activity in response to biotrophs and necrotrophs as well as SA. PMID:25819608

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

    PubMed

    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.

  4. Genotoxicity and molecular response of silver nanoparticle (NP)-based hydrogel

    PubMed Central

    2012-01-01

    Background Since silver-nanoparticles (NPs) possess an antibacterial activity, they were commonly used in medical products and devices, food storage materials, cosmetics, various health care products, and industrial products. Various silver-NP based medical devices are available for clinical uses, such as silver-NP based dressing and silver-NP based hydrogel (silver-NP-hydrogel) for medical applications. Although the previous data have suggested silver-NPs induced toxicity in vivo and in vitro, there is lack information about the mechanisms of biological response and potential toxicity of silver-NP-hydrogel. Methods In this study, the genotoxicity of silver-NP-hydrogel was assayed using cytokinesis-block micronucleus (CBMN). The molecular response was studied using DNA microarray and GO pathway analysis. Results and discussion The results of global gene expression analysis in HeLa cells showed that thousands of genes were up- or down-regulated at 48 h of silver-NP-hydrogel exposure. Further GO pathway analysis suggested that fourteen theoretical activating signaling pathways were attributed to up-regulated genes; and three signal pathways were attributed to down-regulated genes. It was discussed that the cells protect themselves against silver NP-mediated toxicity through up-regulating metallothionein genes and anti-oxidative stress genes. The changes in DNA damage, apoptosis and mitosis pathway were closely related to silver-NP-induced cytotoxicity and chromosome damage. The down-regulation of CDC14A via mitosis pathway might play a role in potential genotoxicity induced by silver-NPs. Conclusions The silver-NP-hydrogel induced micronuclei formation in cellular level and broad spectrum molecular responses in gene expression level. The results of signal pathway analysis suggested that the balances between anti-ROS response and DNA damage, chromosome instability, mitosis inhibition might play important roles in silver-NP induced toxicity. The inflammatory factors

  5. Molecular characteristics of Illicium verum extractives to activate acquired immune response

    PubMed Central

    Peng, Wanxi; Lin, Zhi; Wang, Lansheng; Chang, Junbo; Gu, Fangliang; Zhu, Xiangwei

    2015-01-01

    Illicium verum, whose extractives can activate the demic acquired immune response, is an expensive medicinal plant. However, the rich extractives in I. verum biomass were seriously wasted for the inefficient extraction and separation processes. In order to further utilize the biomedical resources for the good acquired immune response, the four extractives were obtained by SJYB extraction, and then the immunology moleculars of SJYB extractives were identified and analyzed by GC–MS. The result showed that the first-stage extractives contained 108 components including anethole (40.27%), 4-methoxy-benzaldehyde (4.25%), etc.; the second-stage extractives had 5 components including anethole (84.82%), 2-hydroxy-2-(4-methoxy-phenyl)-n-methyl-acetamide (7.11%), etc.; the third-stage extractives contained one component namely anethole (100%); and the fourth-stage extractives contained 5 components including cyclohexyl-benzene (64.64%), 1-(1-methylethenyl)-3-(1-methylethyl)-benzene (17.17%), etc. The SJYB extractives of I. verum biomass had a main retention time between 10 and 20 min what’s more, the SJYB extractives contained many biomedical moleculars, such as anethole, eucalyptol, [1S-(1α,4aα,10aβ)]-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-1-phenanthrenecarboxylic acid, stigmast-4-en-3-one, γ-sitosterol, and so on. So the functional analytical results suggested that the SJYB extractives of I. verum had a function in activating the acquired immune response and a huge potential in biomedicine. PMID:27081359

  6. Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation.

    PubMed

    Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

    2016-01-01

    The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients. PMID:27023397

  7. Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation.

    PubMed

    Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

    2016-01-01

    The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients.

  8. Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation

    PubMed Central

    Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

    2016-01-01

    The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients. PMID:27023397

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

    PubMed Central

    Miyazaki, Ryohei; Anayama, Takashi; Hirohashi, Kentaro; Okada, Hironobu; Kume, Motohiko; Orihashi, Kazumasa

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:27070423

  10. A perspective on nonresonant and resonant electronic response theory for time-dependent molecular properties.

    PubMed

    Norman, Patrick

    2011-12-14

    The development of electronic response theory in quantum chemistry has been reviewed, starting from the early 1970's and reaching the current state-of-the-art. The general theory has been applied to the calculation of a large number of spectroscopic parameters over the years, and it has been implemented for the majority of standard electronic structure methods. Two formulations of response theory, the Ehrenfest expectation value and the quasi-energy derivative formulation, have turned into leading alternatives for the derivation of computationally tractable expressions of response functions, and they are here reviewed with an attempt to, as far as possible, leave out technical details. A set of four steps are identified as common in derivations of response functions, and the two formulations are compared along this series of steps. Particular emphasis is given to the situation when the oscillation of the weak external electromagnetic field is in resonance with a transition frequency of the system. The formation of physically sound response functions in resonance regions of the spectrum is discussed in light of the causality condition and the Kramers-Kronig relations, and it is achieved in wave function theory by means of the introduction of relaxation parameters in a manner that mimics what one sees in density matrix theory. As a working example, equations are illustrated by their application to a two-state model for para-nitroaniline including the ground and the lowest charge-transfer state in the electric dipole approximation.

  11. Expression of Toll-Like Receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder.

    PubMed

    Kéri, Szabolcs; Szabó, Csilla; Kelemen, Oguz

    2014-08-01

    In recent years, increased attention has been paid to the inflammatory mechanisms of major depressive disorder (MDD). The aim of the present study was to investigate pro-inflammatory pathways related to the "leaky gut" hypothesis of MDD, which is based on the putative intestinal translocation of Gram-negative bacteria and a subsequent abnormal immune response mediated by the Toll-Like Receptor-4 (TLR-4) pathway. 50 patients with first-episode MDD and 30 healthy control subjects participated in the study. Real-time quantitative PCR was used to measure TLR-4 and TLR-2 RNA from peripheral mononuclear blood cells, as well as the expression of NF-κβ, a key transcription factor of the pro-inflammatory response. TLR-4 protein expression was determined by using flow cytometry. TLR-2 served as a control molecule. Low-grade inflammation was characterized by the measurement of interleukin-6 (IL-6) and C-reactive protein (CRP). Bacterial translocation was investigated by the measurement of the 16S rRNA subunit (16S rDNA) of intestinal microbiota in the blood plasma of the participants. We performed these analyses before (t1) and after (t2) cognitive-behavioral therapy (CBT) in MDD. The healthy control subjects were also assessed two times. We found significantly elevated expressions of all three markers (TLR-4 RNA and protein, NF-κβ RNA) and 16S rDNA in MDD at t1 relative to healthy control subjects. These markers showed a significant decrease during CBT (t1>t2 in MDD). We observed no between-group differences and changes in the case of TLR-2. Greater reduction of pro-inflammatory markers during CBT was associated with more pronounced clinical improvement. IL-6 and CRP displayed a moderately elevated level in MDD and did not change during CBT. In conclusion, TLR-4 signaling is up-regulated in newly diagnosed patients with MDD, which may be related to bacterial translocation or to the presence of various damage-associated molecular patterns. Clinical improvement during

  12. In silico prediction of peptide binding affinity to class I mouse major histocompatibility complexes: a comparative molecular similarity index analysis (CoMSIA) study.

    PubMed

    Hattotuwagama, Channa K; Doytchinova, Irini A; Flower, Darren R

    2005-01-01

    Current methods for the in silico identification of T cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate prediction of peptide-major histocompatibility complex (MHC) affinity. A three-dimensional quantitative structure-activity relationship (3D-QSAR) for the prediction of peptide binding to class I MHC molecules was established using the comparative molecular similarity index analysis (CoMSIA) method. Three MHC alleles were studied: H2-D(b), H2-K(b), and H2-K(k). Models were produced for each allele. Each model consisted of five physicochemical descriptors-steric bulk, electrostatic potentials, hydrophobic interactions, and hydrogen-bond donor and hydrogen-bond acceptor abilities. The models have an acceptable level of predictivity: cross-validation leave-one-out statistical terms q2 and SEP (standard error of prediction) ranged between 0.490 and 0.679 and between 0.525 and 0.889, respectively. The non-cross-validated statistical terms r2 and SEE (standard error of estimate) ranged between 0.913 and 0.979 and between 0.167 and 0.248, respectively. The use of coefficient contour maps, which indicate favored and disfavored areas for each position of the MHC-bound peptides, allowed the binding specificity of each allele to be identified, visualized, and understood. The present study demonstrates the effectiveness of CoMSIA as a method for studying peptide-MHC interactions. The peptides used in this study are available on the Internet (http://www.jenner.ac.uk/AntiJen). The partial least-squares method is available commercially in the SYBYL molecular modeling software package. PMID:16180918

  13. Stress response and adaptation: a new molecular toolkit for the 21st century.

    PubMed

    Storey, Kenneth B; Wu, Cheng-Wei

    2013-08-01

    Much research in comparative biochemistry is focused on understanding the molecular mechanisms that allow organisms to adapt to and survive diverse environmental challenges. In recent years, genomic and proteomic approaches have been key drivers of advancement in the field, for example, providing knowledge about gene and protein expression, regulation of signal transduction pathways, and functional control of enzymes/proteins by reversible protein phosphorylation. Advances in comparative biochemistry have always drawn upon conceptual and technological advances that arise from "mainline" biochemistry and molecular biology, often from medical models. The present article discusses three such advances that will have major impacts on comparative biochemistry in the 21st century. The first is the crucial role of posttranslational modification in metabolic control, expanding outwards from reversible phosphorylation to explore the individual and interacting effects of protein modification by acetylation, methylation, SUMOylation and O-GlcNAcylation, among others. The second is the newly recognized role of non-coding RNA in the regulation of gene expression, particularly the action of microRNAs. The third is the emergence of powerful multiplex technology that allows rapid, high-throughput detection of analytes and will revolutionize RNA and protein profiling in the comparative biochemistry laboratory. Commercial tools such as Luminex allow researchers to simultaneously quantify up to 100 different analytes in a single sample, thereby creating broad functional analyses of metabolism and cell signaling pathways.

  14. Molecular Origins of Higher Harmonics in Large-Amplitude Oscillatory Shear Flow: Shear Stress Response

    NASA Astrophysics Data System (ADS)

    Gilbert, Peter; Giacomin, A. Jeffrey; Schmalzer, Andrew; Bird, R. B.

    Recent work has focused on understanding the molecular origins of higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. These higher harmonics have been explained using only the orientation distribution of a dilute suspension of rigid dumbbells in a Newtonian fluid, which neglects molecular interactions and is the simplest relevant molecular model of polymer viscoelasticity [R.B. Bird et al., J Chem Phys, 140, 074904 (2014)]. We explore these molecular interactions by examining the Curtiss-Bird model, a kinetic molecular theory that accounts for restricted polymer motions arising when chains are concentrated [Fan and Bird, JNNFM, 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ =0 corresponds to reptation, ɛ > 1 1 8 8 to rod-climbing, 1 1 2 2 >= ɛ >= 3 3 4 4 to reasonable shear-thinning predictions in steady simple shear flow, and ɛ =1 to a dilute solution of chains. We examine the shapes of the shear stress versus shear rate loops for the special cases, ɛ = 0 , 1 0 , 1 8 , 3 3 8 8 8 , 3 3 8 8 , 1 , of the Curtiss-Bird model, and we compare these with those

  15. Integrating the cell stress response: a new view of molecular chaperones as immunological and physiological homeostatic regulators.

    PubMed

    Henderson, Brian

    2010-01-01

    The response of cells to stress was first documented in the 1960s and 1970s and the molecular nature of the families of proteins that subserve this vital response, the molecular chaperones, were identified and subjected to critical study in the period from the late 1980s. This resulted in the rapidly advancing new field of protein folding and its role in cellular function. Emerging at the same time, but initially largely ignored, were reports that molecular chaperones could be released by cells and exist on the outer plasma membrane or in the body fluids. These secreted molecular chaperones were found to have intercellular signalling functions. There is now a growing body of evidence to support the hypothesis that molecular chaperones have properties ascribed to the Roman god Janus, the god of gates, doors, beginnings and endings, whose two faces point in different directions. Molecular chaperones appear to have one set of key functions within the cell and, potentially, a separate set of functions when they exist on the cell surface or in the various fluid phases of the body. Thus, it is a likely hypothesis that secreted molecular chaperones act as an additional level of homeostatic control possibly linking cellular stress to physiological systems such as the immune system. This review concentrates on three key molecular chaperones: Hsp10, Hsp60 and the Hsp70 family for which most information is available. An important consideration is the role that these proteins may play in human disease and in the treatment of human disease.

  16. Insights into molecular and metabolic events associated with fruit response to post-harvest fungal pathogens

    PubMed Central

    Alkan, Noam; Fortes, Ana M.

    2015-01-01

    Due to post-harvest losses more than 30% of harvested fruits will not reach the consumers’ plate. Fungal pathogens play a key role in those losses, as they cause most of the fruit rots and the customer complaints. Many of the fungal pathogens are already present in the unripe fruit but remain quiescent during fruit growth until a particular phase of fruit ripening and senescence. The pathogens sense the developmental change and switch into the devastating necrotrophic life style that causes fruit rotting. Colonization of unripe fruit by the fungus initiates defensive responses that limit fungal growth and development. However, during fruit ripening several physiological processes occur that correlate with increased fruit susceptibility. In contrast to plant defenses in unripe fruit, the defense posture of ripe fruit entails a different subset of defense responses that will end with fruit rotting and losses. This review will focus on several aspects of molecular and metabolic events associated with fleshy fruit responses induced by post-harvest fungal pathogens during fruit ripening. PMID:26539204

  17. Cellular, physiological, and molecular adaptive responses of Erwinia amylovora to starvation.

    PubMed

    Santander, Ricardo D; Oliver, James D; Biosca, Elena G

    2014-05-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants distributed worldwide. This bacterium is a nonobligate pathogen able to survive outside the host under starvation conditions, allowing its spread by various means such as rainwater. We studied E. amylovora responses to starvation using water microcosms to mimic natural oligotrophy. Initially, survivability under optimal (28 °C) and suboptimal (20 °C) growth temperatures was compared. Starvation induced a loss of culturability much more pronounced at 28 °C than at 20 °C. Natural water microcosms at 20 °C were then used to characterize cellular, physiological, and molecular starvation responses of E. amylovora. Challenged cells developed starvation-survival and viable but nonculturable responses, reduced their size, acquired rounded shapes and developed surface vesicles. Starved cells lost motility in a few days, but a fraction retained flagella. The expression of genes related to starvation, oxidative stress, motility, pathogenicity, and virulence was detected during the entire experimental period with different regulation patterns observed during the first 24 h. Further, starved cells remained as virulent as nonstressed cells. Overall, these results provide new knowledge on the biology of E. amylovora under conditions prevailing in nature, which could contribute to a better understanding of the life cycle of this pathogen.

  18. Genome-Wide Transcriptional Profiling and Metabolic Analysis Uncover Multiple Molecular Responses of the Grass Species Lolium perenne Under Low-Intensity Xenobiotic Stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Heijnen, David; Michon-Coudouel, Sophie; Sulmon, Cécile; Gouesbet, Gwenola

    2015-01-01

    Lolium perenne, which is a major component of pastures, lawns, and grass strips, can be exposed to xenobiotic stresses due to diffuse and residual contaminations of soil. L. perenne was recently shown to undergo metabolic adjustments in response to sub-toxic levels of xenobiotics. To gain insight in such chemical stress responses, a de novo transcriptome analysis was carried out on leaves from plants subjected at the root level to low levels of xenobiotics, glyphosate, tebuconazole, and a combination of the two, leading to no adverse physiological effect. Chemical treatments influenced significantly the relative proportions of functional categories and of transcripts related to carbohydrate processes, to signaling, to protein-kinase cascades, such as Serine/Threonine-protein kinases, to transcriptional regulations, to responses to abiotic or biotic stimuli and to responses to phytohormones. Transcriptomics-based expressions of genes encoding different types of SNF1 (sucrose non-fermenting 1)-related kinases involved in sugar and stress signaling or encoding key metabolic enzymes were in line with specific qRT-PCR analysis or with the important metabolic and regulatory changes revealed by metabolomic analysis. The effects of pesticide treatments on metabolites and gene expression strongly suggest that pesticides at low levels, as single molecule or as mixture, affect cell signaling and functioning even in the absence of major physiological impact. This global analysis of L. perenne therefore highlighted the interactions between molecular regulation of responses to xenobiotics, and also carbohydrate dynamics, energy dysfunction, phytohormones and calcium signaling. PMID:26734031

  19. Physiological and molecular responses of Lactuca sativa to colonization by Salmonella enterica serovar Dublin.

    PubMed

    Klerks, M M; van Gent-Pelzer, M; Franz, E; Zijlstra, C; van Bruggen, A H C

    2007-08-01

    This paper describes the physiological and molecular interactions between the human-pathogenic organism Salmonella enterica serovar Dublin and the commercially available mini Roman lettuce cv. Tamburo. The association of S. enterica serovar Dublin with lettuce plants was first determined, which indicated the presence of significant populations outside and inside the plants. The latter was evidenced from significant residual concentrations after highly efficient surface disinfection (99.81%) and fluorescence microscopy of S. enterica serovar Dublin in cross sections of lettuce at the root-shoot transition region. The plant biomass was reduced significantly compared to that of noncolonized plants upon colonization with S. enterica serovar Dublin. In addition to the physiological response, transcriptome analysis by cDNA amplified fragment length polymorphism analysis also provided clear differential gene expression profiles between noncolonized and colonized lettuce plants. From these, generally and differentially expressed genes were selected and identified by sequence analysis, followed by reverse transcription-PCR displaying the specific gene expression profiles in time. Functional grouping of the expressed genes indicated a correlation between colonization of the plants and an increase in expressed pathogenicity-related genes. This study indicates that lettuce plants respond to the presence of S. enterica serovar Dublin at physiological and molecular levels, as shown by the reduction in growth and the concurrent expression of pathogenicity-related genes. In addition, it was confirmed that Salmonella spp. can colonize the interior of lettuce plants, thus potentially imposing a human health risk when processed and consumed.

  20. Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia.

    PubMed

    Cross, N C P; White, H E; Colomer, D; Ehrencrona, H; Foroni, L; Gottardi, E; Lange, T; Lion, T; Machova Polakova, K; Dulucq, S; Martinelli, G; Oppliger Leibundgut, E; Pallisgaard, N; Barbany, G; Sacha, T; Talmaci, R; Izzo, B; Saglio, G; Pane, F; Müller, M C; Hochhaus, A

    2015-05-01

    Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants. PMID:25652737

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Early molecular response in chronic myeloid leukemia and halving time: Latest evidences.

    PubMed

    Breccia, Massimo; Molica, Matteo; Colafigli, Gioia; Massaro, Fulvio; Alimena, Giuliana

    2016-09-01

    Achieving a BCR-ABL/ABL ratio <10% at 3 months has become an important goal of treatment for chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors. Several evidences showed that this early molecular response (EMR) is associated with positive long-term outcome in terms of overall survival and progression-free survival, but a consensus has not been reached when this goal is not achieved. European LeukemiaNet recommendations defined patients as treatment failure only after the 6- month time point. Not all patients that lack EMR have similar outcome and it became important to identify patients before this time point of 3 months. Several groups introduced the concept of "halving time" or "velocity of ratio reduction" that could anticipate the possibility to recognize patients deserving a switch to another treatment. Aim of this review is to summarize all evidences reported on the significance of EMR and how this evaluation changed our perspectives and modified our therapeutic strategies.

  3. Confinement effects on collective water dynamics: Molecular dynamics study of optical Kerr response in silica nanopores

    NASA Astrophysics Data System (ADS)

    Milischuk, Anatoli; Ladanyi, Branka

    2014-03-01

    We report the results of the study of the effects of confinement on collective dynamical properties of water in model nanopores at ambient conditions. The main focus is on approximately cylindrical pores composed of amorphous silica, with diameters ranging from 20 to 40 Å, designed to represent MCM-41 materials. Results for hydrophilic and hydrophobic pores of similar dimensions, but with roughness reduced compared to silica nanopores, are also considered. The main quantity studied is the polarizability anisotropy time correlation function (TCF), which is related to the experimentally-observed optical Kerr effect (OKE) nuclear response. We investigate the effects on this TCF of the reduced molecular translational and rotational water mobility in the layers near the interface. We find that these effects lead to pore diameter dependent slowdown of polarizability anisotropy relaxation, in agreement with OKE experiments. Support from NSF grant number 1213682 is acknowledged.

  4. Defects in tungsten responsible for molecular hydrogen isotope retention after exposure to low energy plasmas

    NASA Astrophysics Data System (ADS)

    Causey, R. A.; Doerner, R.; Fraser, H.; Kolasinski, R. D.; Smugeresky, J.; Umstadter, K.; Williams, R.

    2009-06-01

    Recent work on hydrogen isotope retention in tungsten has shown a substantial fraction of the retained hydrogen to be in the form of molecules. It can be expected that hydrogen permeating through a material such as tungsten, that has a very low solubility for hydrogen, would come out of solution and combine into molecules at voids located throughout the bulk. The purpose of this report is to determine the type of voids responsible for the molecular retention. High purity tungsten provided by Plansee Aktiengesellschaft was first polished, annealed at 1273 K in vacuum for one hour, and then exposed to high fluxes and high fluences of deuterium in the PISCES facility. High resolution Transmission Electron Microscopy was then used to examine the samples for voids. The results of these experiments were used to interpret the expected behavior of tungsten to be used as the divertor of the ITER fusion device.

  5. Cellular and molecular mechanisms for the bone response to mechanical loading

    NASA Technical Reports Server (NTRS)

    Bloomfield, S. A.

    2001-01-01

    To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

  6. Pulmonary fibrosis in response to environmental cues and molecular targets involved in its pathogenesis.

    PubMed

    Yoshida, Toshinori; Ohnuma, Aya; Horiuchi, Haruka; Harada, Takanori

    2011-03-01

    Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents play an etiologic role in the pathogenesis of this disease. The agents discussed in this review include beryllium, nylon flock, textile printing aerosols, polyvinyl chloride and didecyldimethylammonium chloride. The authors also describe a variety of animal models, including genetically modified mice, in order to investigate the molecular mechanism of pulmonary fibrosis, focusing on chemokine receptors, regulatory T cells and transforming growth factor-β and bone morphogenetic protein signaling. Overall, we propose the concept of toxicological pulmonary fibrosis as a lung disease induced in response to environmental cues.

  7. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

    PubMed Central

    Wardyn, Joanna D.; Ponsford, Amy H.; Sanderson, Christopher M.

    2015-01-01

    In most tissues, cells are exposed to frequent changes in levels of oxidative stress and inflammation. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-κB (NF-κB) are the two key transcription factors that regulate cellular responses to oxidative stress and inflammation respectively. Pharmacological and genetic studies suggest that there is functional cross-talk between these two important pathways. The absence of Nrf2 can exacerbate NF-κB activity leading to increased cytokine production, whereas NF-κB can modulate Nrf2 transcription and activity, having both positive and negative effects on the target gene expression. This review focuses on the potentially complex molecular mechanisms that link the Nrf2 and NF-κB pathways and the importance of designing more effective therapeutic strategies to prevent or treat a broad range of neurological disorders. PMID:26551702

  8. Molecular defense responses in roots and the rhizosphere against Fusarium oxysporum

    PubMed Central

    Chen, Yi Chung; Kidd, Brendan N; Carvalhais, Lilia C; Schenk, Peer M

    2014-01-01

    Plants face many different concurrent and consecutive abiotic and biotic stresses during their lifetime. Roots can be infected by numerous pathogens and parasitic organisms. Unlike foliar pathogens, root pathogens have not been explored enough to fully understand root-pathogen interactions and the underlying mechanism of defense and resistance. PR gene expression, structural responses, secondary metabolite and root exudate production, as well as the recruitment of plant defense–assisting “soldier” rhizosphere microbes all assist in root defense against pathogens and herbivores. With new high-throughput molecular tools becoming available and more affordable, now is the opportune time to take a deep look below the ground. In this addendum, we focus on soil-borne Fusarium oxysporum as a pathogen and the options plants have to defend themselves against these hard-to-control pathogens. PMID:25482759

  9. Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis

    PubMed Central

    Yoshida, Toshinori; Ohnuma, Aya; Horiuchi, Haruka; Harada, Takanori

    2011-01-01

    Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents play an etiologic role in the pathogenesis of this disease. The agents discussed in this review include beryllium, nylon flock, textile printing aerosols, polyvinyl chloride and didecyldimethylammonium chloride. The authors also describe a variety of animal models, including genetically modified mice, in order to investigate the molecular mechanism of pulmonary fibrosis, focusing on chemokine receptors, regulatory T cells and transforming growth factor-β and bone morphogenetic protein signaling. Overall, we propose the concept of toxicological pulmonary fibrosis as a lung disease induced in response to environmental cues. PMID:22272040

  10. Molecular and immunogenetic analysis of major histocompatibility haplotypes in Northern Bobwhite enable direct identification of corresponding haplotypes in an endangered subspecies, the Masked Bobwhite

    USGS Publications Warehouse

    Drake, B.M.; Goto, R.M.; Miller, M.M.; Gee, G.F.; Briles, W.E.

    1999-01-01

    The major histocompatibility complex (MHC) is a group of genetic loci coding for haplotypes that have been associated with fitness traits in mammals and birds. Such associations suggest that MHC diversity may be an indicator of overall genetic fitness of endangered or threatened species. The MHC haplotypes of a captive population of 12 families of northern bobwhites (Colinus virginianus) were identified using a combination of immunogenetic and molecular techniques. Alloantisera were produced within families of northern bobwhites and were then tested for differential agglutination of erythrocytes of all members of each family. The pattern of reactions determined from testing these alloantisera identified a single genetic system of alloantigens in the northern bobwhites, resulting in the assignment of a tentative genotype to each individual within the quail families. Restriction fragment patterns of the DNA of each bird were determined using the chicken MHC B-G cDNA probe bg11. The concordance between the restriction fragment patterns and the alloantisera reactions showed that the alloantisera had identified the MHC of the northern bobwhite and supported the tentative genotype assignments, identifying at least 12 northern bobwhite MHC haplotypes.

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

    PubMed

    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. PMID:26433650

  12. Microsecond Molecular Dynamics Simulations of Intrinsically Disordered Proteins Involved in the Oxidative Stress Response

    PubMed Central

    Cino, Elio A.; Wong-ekkabut, Jirasak; Karttunen, Mikko; Choy, Wing-Yiu

    2011-01-01

    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. PMID:22125611

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

    PubMed

    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.

  14. The Combined Influence of Molecular Weight and Temperature on the Aging and Viscoelastic Response of a Glassy Thermoplastic Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2000-01-01

    The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC-SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of five materials of different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have higher creep compliance and creep rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of M (bar) (sub w) 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly. The short-term creep compliance data were used in association with Struik's effective time theory to predict the long-term creep compliance behavior for the different molecular weights. At long timescales, physical aging serves to significantly decrease the creep compliance and creep rate of all the materials tested.

  15. The Effectiveness of an Electronic Student Response System in Teaching Biology to the Non-Major Utilizing Nine Group-Paced, Linear Programs.

    ERIC Educational Resources Information Center

    Bessler, William Carl

    This paper presents the procedures, results, and conclusions of a study designed to determine the effectiveness of an electronic student response system in teaching biology to the non-major. Nine group-paced linear programs were used. Subjects were 664 college students divided into treatment and control groups. The effectiveness of the response…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Perception of Global Climate Change as a Mediator of the Effects of Major and Religious Affiliation on College Students' Environmentally Responsible Behavior

    ERIC Educational Resources Information Center

    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,…

  18. Recent Advances in Understanding the Molecular Mechanisms Regulating the Root System Response to Phosphate Deficiency in Arabidopsis.

    PubMed

    Bouain, Nadia; Doumas, Patrick; Rouached, Hatem

    2016-08-01

    Phosphorus (P) is an essential macronutrient for plant growth and development. Inorganic phosphate (Pi) is the major form of P taken up from the soil by plant roots. It is well established that under Pi deficiency condition, plant roots undergo striking morphological changes; mainly a reduction in primary root length while increase in lateral root length as well as root hair length and density. This typical phenotypic change reflects complex interactions with other nutrients such as iron, and involves the activity of a large spectrum of plant hormones. Although, several key proteins involved in the regulation of root growth under Pi-deficiency have been identified in Arabidopsis, how plants adapt roots system architecture in response to Pi availability remains an open question. In the current post-genomic era, state of the art technologies like high-throughput phenotyping and sequencing platforms,"omics" methods, together with the widespread use of system biology and genome-wide association studies will help to elucidate the genetic architectures of root growth on different Pi regimes. It is clear that the large-scale characterization of molecular systems will improve our understanding of nutrient stress phenotype and biology. Herein, we summarize the recent advances and future directions towards a better understanding of Arabidopsis root developmental programs functional under Pi deficiency. Such a progress is necessary to devise strategies to improve the Pi use efficiency in plants that is an important issue for agriculture. PMID:27499680

  19. Molecular, behavioral, and performance responses of juvenile largemouth bass acclimated to an elevated carbon dioxide environment.

    PubMed

    Dennis, Clark E; Adhikari, Shivani; Wright, Adam W; Suski, Cory D

    2016-04-01

    Aquatic hypercarbia, either naturally occurring or anthropogenically induced, can have extensive impacts on aquatic environments and resident organisms. While the impact of acute hypercarbia exposure on the behavior and physiology of fishes has been well studied, relatively little work has examined the physiological impact and acclimation capacity of fishes to chronic hypercarbia. To better understand the impacts of prolonged hypercarbia exposure, largemouth bass were held at ambient CO2 (13 mg L(-1)) and elevated CO2 (31 mg L(-1); ≈ 21,000 µatm) for 58 days. Following this acclimation period, fish were subjected to three separate, yet complementary, experiments: (1) acute hypercarbia challenge of 120 mg L(-1) CO2 for 1 h to quantify physiological and molecular responses; (2) hypercarbia avoidance challenge to compare CO2 agitation and avoidance responses; and (3) swim performance challenge to quantify burst swimming performance. Acclimation to 31 mg L(-1) CO2 resulted in a significant constitutive upregulation of c-fos expression in erythrocytes, combined with significant constitutive expression of hsp70 in both gill and erythrocytes, relative to controls. Largemouth bass acclimated to elevated CO2 also had a reduced glucose response (relative to controls) following an acute CO2 exposure, indicating a reduced stress response to CO2 stressors. In addition, largemouth bass acclimated to elevated CO2 conditions required 50 % higher CO2 concentrations to illicit agitation behaviors and displayed prolonged burst swimming abilities in high CO2 environments relative to controls. Together, results demonstrate that largemouth bass exposed to chronic hypercarbia may possess a physiological advantage during periods of elevated CO2 relative to naïve fish, which may permit increased performance in hypercarbia. PMID:26758610

  20. Molecular cloning and characterization of wheat calreticulin (CRT) gene involved in drought-stressed responses.

    PubMed

    Jia, Xiao-Yun; Xu, Chong-Yi; Jing, Rui-Lian; Li, Run-Zhi; Mao, Xin-Guo; Wang, Ji-Ping; Chang, Xiao-Ping

    2008-01-01

    Calreticulin (CRT) is a highly conserved and ubiquitously expressed Ca(2+)-binding protein in multicellular eukaryotes. CRT plays a crucial role in many cellular processes including Ca(2+) storage and release, protein synthesis, and molecular chaperone activity. To elucidate the function of CRTs in plant responses against drought, a main abiotic stress limiting cereal crop production worldwide, a full-length cDNA encoding calreticulin protein namely TaCRT was isolated from wheat (Triticum aestivum L.). The deduced amino acid sequence of TaCRT shares high homology with other plant CRTs. Phylogenetic analysis indicates that TaCRT cDNA clone encodes a wheat CRT3 isoform. Southern analysis suggests that the wheat genome contains three copies of TaCRT. Subcellular locations of TaCRT were the cytoplasm and nucleus, evidenced by transient expression of GFP fused with TaCRT in onion epidermal cells. Enhanced accumulation of TaCRT transcript was observed in wheat seedlings in response to PEG-induced drought stress. To investigate further whether TaCRT is involved in the drought-stress response, transgenic plants were constructed. Compared to the wild-type and GFP-expressing plants, TaCRT-overexpressing tobacco (Nicotiana benthamiana) plants grew better and exhibited less wilt under the drought stress. Moreover, TaCRT-overexpressing plants exhibited enhanced drought resistance to water deficit, as shown by their capacity to maintain higher WUE (water use efficiency), WRA (water retention ability), RWC (relative water content), and lower MDR (membrane damaging ratio) (P < or = 0.01) under water-stress conditions. In conclusion, a cDNA clone encoding wheat CRT was successfully isolated and the results suggest that TaCRT is involved in the plant response to drought stress, indicating a potential in the transgenic improvements of plant water-stress.

  1. Responses to the AAR-Teagle White Paper: "The Religious Studies Major in a Post-9/11 World"

    ERIC Educational Resources Information Center

    Webster, Jane S.; Buckley, James J.; Jensen, Tim; Floyd-Thomas, Stacey

    2011-01-01

    In October 2008 The American Academy of Religion published the findings of an eighteen month study (conducted with funding from the Teagle Foundation) on "The Religious Studies Major in a Post-9/11 World: New Challenges, New Opportunities." Re-published here, this AAR-Teagle White Paper provides the opportunity for four respondents to raise issues…

  2. Different cytokines are required for induction and maintenance of the Th2 type response in DBA/2 mice resistant to infection with Leishmania major.

    PubMed

    Nashed, B F; Maekawa, Y; Takashima, M; Zhang, T; Ishii, K; Dainichi, T; Ishikawa, H; Sakai, T; Hisaeda, H; Himeno, K

    2000-10-01

    Experimental cutaneous leishmaniasis is a useful model in studying the mechanism regulating immune responses between T helper type 1 (Th1) and Th2. Mice susceptible to Leishmania major infection such as BALB/c (H-2(d)) are associated with the induction of the disease-promoting Th2 response, while the resistant mice such as DBA/2 (H-2(d)) develop the protective Th1 response. To understand the induction mechanism of Th1 and Th2 responses, it is necessary to establish an immunization scheme by which the induction of each Th response can be easily and experimentally controlled. Adjuvants are known to enhance the immune responses through the combined effect of several factors: prolonged release of antigen, migration of cells, mitogenic effect and so forth. When the genetically resistant DBA/2 mice were immunized twice with soluble leishmanial antigen (SLA), emulsified in incomplete Freund's adjuvant (IFA) before L. major inoculation, these mice mounted a Th2 cell response and suffered from progressive infection. While IL-4 and IL-13 were upregulated early after the infection in both healer and non-healer groups of mice, IL-5 and IL-10 were upregulated only in non-healer mice. From these results, IL-5 and IL-10 appear to have an important role, at least in the early phases of the infection, rather than IL-4 and IL-13 in establishing the disease-promoting Th2 response in leishmaniasis. Further, IL-9 was found to be expressed in both BALB/c and DBA/2 mice immunized with IFA/SLA. This cytokine may support the establishment of a Th2 response in these mice. Therefore it is suggested that Th2 cytokines play different roles between priming and maintaining the Th2 immune response after the infection.

  3. Frictional Response of Molecularly Thin Liquid Polymer Films Subject to Constant Shear Stress

    NASA Astrophysics Data System (ADS)

    Tschirhart, Charles; Troian, Sandra

    2014-03-01

    Measurements of the frictional response of nanoscale viscous films are typically obtained using the surface force apparatus in which a fluid layer is confined between smooth solid substrates approaching at constant speed or force. The squeezing pressure causes lateral flow from which the shear viscosity can be deduced. Under these conditions however, molecularly thin films tend to solidify wholly or partially and estimates of the shear viscosity can exceed those in macroscale films by many orders of magnitude. This problem can be avoided altogether by examining the response of an initially flat, supported, free surface film subject to comparable values of surface shear stress by application of an external inert gas stream. This method was first conceived by Derjaguin in 1944; more recent studies by Mate et al. at IBM Almaden on complex polymeric systems have uncovered fluid layering and other interesting behaviors. The only drawback is that this alternative technique requires an accurate model for interface distortion. We report on ellipsometric measurements of ultrathin polymeric films in efforts to determine whether the usual interface equations for free surface films based purely on continuum models can be properly extended to nanoscale films. Supported by a Fred and Jean Felberg Fellowship and G. W. Housner Student Discovery Fund.

  4. Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

    PubMed Central

    Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

    2010-01-01

    Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID: