Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

Science.gov (United States)

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

Science.gov (United States)

Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

2016-12-01

While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

Multiple resistance to pirimiphos-methyl and bifenthrin in Tribolium castaneum involves the activity of lipases, esterases, and laccase2.

Science.gov (United States)

Julio, Alison Henrique Ferreira; Gigliolli, Adriana Aparecida Sinópolis; Cardoso, Kátia Aparecida Kern; Drosdoski, Sandro Daniel; Kulza, Rodrigo Amaral; Seixas, Flávio Augusto Vicente; Ruvolo-Takasusuki, Maria Claudia Colla; de Souza, Cristina Giatti Marques; Lapenta, Ana Silvia

2017-05-01

Several recent studies have elucidated the molecular mechanisms that confer insecticide resistance on insect pests. However, little is known about multiple resistance in red flour beetle (Tribolium castaneum) at molecular level. The multiple resistance is characterized as resistance to different classes of insecticides that have different target sites, and is mediated by several enzymatic systems. In this study, we investigated the biochemical and molecular mechanisms involved in multiple resistance of T. castaneum to bifenthrin (pyrethroid [Pyr]) and pirimiphos-methyl (organophosphate [Org]). We used artificial selection, biochemical and in silico approaches including structural computational biology. After five generations of artificial selection in the presence of bifenthrin (F5Pyr) or pirimiphos-methyl (F5Org), we found high levels of multiple resistance. The hierarchical enzymatic cluster revealed a pool of esterases (E), lipases (LIPs) and laccase2 (LAC2) potentially contributing to the resistance in different ways throughout development, after one or more generations in the presence of insecticides. The enzyme-insecticide interaction network indicated that E2, E3, LIP3, and LAC2 are enzymes potentially required for multiple resistance phenotype. Kinetic analysis of esterases from F5Pyr and F5Org showed that pirimiphos-methyl and specially bifenthrin promote enzyme inhibition, indicating that esterases mediate resistance by sequestering bifenthrin and pirimiphos-methyl. Our computational data were in accordance with kinetic results, indicating that bifenthrin has higher affinity at the active site of esterase than pirimiphos-methyl. We also report the capability of these insecticides to modify the development in T. castaneum. Our study provide insights into the biochemical mechanisms employed by T. castaneum to acquire multiple resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay

Energy Technology Data Exchange (ETDEWEB)

Cerase, Alfonso; Gennari, Paola; Monti, Lucia; Venturi, Carlo [Azienda Ospedaliera Universitaria Senese, Unit of Diagnostic and Therapeutic Neuroradiology, and InterDepartmental Center of Nuclear Magnetic Resonance, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Tarantino, Annachiara; Muccio, Carmine Franco [Azienda Ospedaliera ' G. Rummo' , Unit of Neuroradiology, Department of Neurosciences, Benevento (Italy); Gozzetti, Alessandro [University of Siena, Unit of Hematology and Transplants, Policlinico ' Santa Maria alle Scotte' , Siena (Italy); Di Blasi, Arturo [Azienda Ospedaliera ' G. Rummo' , Unit of Pathology, Department of Oncology, Benevento (Italy)

2008-08-15

The purpose of this pictorial essay is to increase awareness of the clinical presentation, neuroradiological findings, treatment options, and neuroradiological follow-up of plasmacytomas and multiple myeloma with intracranial growth. This pictorial essay reviews the clinical features and neuroradiological findings in seven patients (four women, three men; age range at diagnosis 62-82 years) followed in two institutions. Six patients, one with IgG-{kappa} plasmacytoma, and five with IgG-{kappa}(n=3), IgG-{lambda}(n=1), and nonsecretory (n=1) multiple myeloma, had been seen over a period of 9 years in one institution, and the other patient with IgG-{kappa} plasmacytoma had been seen over a period of 3.5 years in the other. Intracranial involvement is rare, most frequently resulting from osseous lesions in the cranial vault, skull base, nose, or paranasal sinuses. Primary dural or leptomeningeal involvement is rarer. Some typical findings of a dural and/or osseous plasmacytoma include iso- to hyperdensity on CT scan, T1 equal to high signal intensity and T2 markedly hypointense signal on MRI, and high vascularity possibly documented on intraarterial digital subtraction angiography. However, the neuroradiological findings generally lack specificity, since they are generally no different from those of meningioma, metastasis, lymphoma, dural sarcoma, plasma cell granuloma, infectious meningitis, and leptomeningeal carcinomatosis. The spectrum of clinical and neuroradiological evaluation shows that intracranial involvement from plasmacytoma and multiple myeloma must be taken into account in the differential diagnosis of cranial osseous and meningeal disease. (orig.)

Learning with multiple representations: an example of a revision lesson in mechanics

Science.gov (United States)

Wong, Darren; Poo, Sng Peng; Eng Hock, Ng; Loo Kang, Wee

2011-03-01

We describe an example of learning with multiple representations in an A-level revision lesson on mechanics. The context of the problem involved the motion of a ball thrown vertically upwards in air and studying how the associated physical quantities changed during its flight. Different groups of students were assigned to look at the ball's motion using various representations: motion diagrams, vector diagrams, free-body diagrams, verbal description, equations and graphs, drawn against time as well as against displacement. Overall, feedback from students about the lesson was positive. We further discuss the benefits of using computer simulation to support and extend student learning.

Clinical and biological features of multiple myeloma involving the gastrointestinal system.

Science.gov (United States)

Talamo, Giampaolo; Cavallo, Federica; Zangari, Maurizio; Barlogie, Bart; Lee, Choon-Kee; Pineda-Roman, Mauricio; Kiwan, Elias; Krishna, Somashekar; Tricot, Guido

2006-07-01

We report 24 cases of multiple myeloma (MM) with involvement of the gastrointestinal (GI) system. We found a strong association with high A lactate dehydrogenase levels, plasmablastic morphology, and A unfavorable karyotype. GI involvement at the time of initial diagnosis was much rarer than later in the course of the disease. The A median survival after diagnosis of GI involvement was 7 months. Among 13 patients treated with stem cell transplantation, the response rate was 92%, and median progression-free survival was 4 months. We conclude that MM involving the GI system is associated with adverse biological features and with short-lasting remissions, even after A high-dose chemotherapy.

Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

Science.gov (United States)

Goodman, Jay I; Watson, Rebecca E

2002-01-01

This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

Energy Technology Data Exchange (ETDEWEB)

Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

2015-03-01

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro

NARCIS (Netherlands)

Erk, van M.J.; Roepman, P.; Lende, van der T.R.; Stierum, R.H.; Aarts, J.M.M.J.G.; Bladeren, van P.J.; Ommen, van B.

2005-01-01

Background Many different mechanisms are involved in nutrient¿related prevention of colon cancer. In this study, a comprehensive assessment of the spectrum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid

Multiple Family Groups for Child Behavior Difficulties: Retention Among Child Welfare-Involved Caregivers

Science.gov (United States)

Gopalan, Geetha; Fuss, Ashley; Wisdom, Jennifer P.

2015-01-01

Purpose: The Multiple Family Group (MFG) service delivery model to reduce childhood disruptive behavior disorders has shown promise in engaging child welfare-involved families. This qualitative study examines caregivers' perceptions of factors that influence retention in MFGs among child welfare-involved families. Methods: Twenty-five…

Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression.

Science.gov (United States)

Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

2015-09-29

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves.

Science.gov (United States)

Kim, Soo Ryang; Kanda, Fumio; Kobessho, Hiroshi; Sugimoto, Koji; Matsuoka, Toshiyuki; Kudo, Masatoshi; Hayashi, Yoshitake

2006-11-07

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

Institute of Scientific and Technical Information of China (English)

Soo Ryang Kim; Fumio Kanda; Hiroshi Kobessho; Koji Sugimoto; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

2006-01-01

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-yearold woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI)disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement.The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Multiple environment single system quantum mechanical/molecular mechanical (MESS-QM/MM) calculations. 1. Estimation of polarization energies.

Science.gov (United States)

Sodt, Alexander J; Mei, Ye; König, Gerhard; Tao, Peng; Steele, Ryan P; Brooks, Bernard R; Shao, Yihan

2015-03-05

In combined quantum mechanical/molecular mechanical (QM/MM) free energy calculations, it is often advantageous to have a frozen geometry for the quantum mechanical (QM) region. For such multiple-environment single-system (MESS) cases, two schemes are proposed here for estimating the polarization energy: the first scheme, termed MESS-E, involves a Roothaan step extrapolation of the self-consistent field (SCF) energy; whereas the other scheme, termed MESS-H, employs a Newton-Raphson correction using an approximate inverse electronic Hessian of the QM region (which is constructed only once). Both schemes are extremely efficient, because the expensive Fock updates and SCF iterations in standard QM/MM calculations are completely avoided at each configuration. They produce reasonably accurate QM/MM polarization energies: MESS-E can predict the polarization energy within 0.25 kcal/mol in terms of the mean signed error for two of our test cases, solvated methanol and solvated β-alanine, using the M06-2X or ωB97X-D functionals; MESS-H can reproduce the polarization energy within 0.2 kcal/mol for these two cases and for the oxyluciferin-luciferase complex, if the approximate inverse electronic Hessians are constructed with sufficient accuracy.

Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

International Nuclear Information System (INIS)

Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

1989-01-01

The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

Pseudomalignant myositis ossificans involving multiple masticatory muscles: Imaging evaluation

International Nuclear Information System (INIS)

Kamalapur, Muralidhar G; Patil, Pritam B; Joshi, Shyamsundar; Shastri, Dinesh

2014-01-01

Myositis ossificans is a rare cause of trismus. We present a case of pseudomalignant myositis ossificans involving medial pterygoid, lateral pterygoid, and temporalis muscles. Patient presented with gross limitation in mouth opening. There was no history of trauma. Computed tomography (CT) images revealed a bone density mass located in the region of medial and lateral pterygoid muscles on the right and temporalis muscle on the left. Magnetic resonance imaging (MRI) showed similar findings. Radiological diagnosis was pseudomalignant myositis ossificans. The masses were resected and histopathologic examination confirmed the above diagnosis. This report describes the characteristic CT and MRI features. The unique feature of this case is the absence of history of trauma with involvement of multiple masticatory muscles, which, to the best of our knowledge, has not been reported before

Multiple Export Mechanisms for mRNAs

Science.gov (United States)

Delaleau, Mildred; Borden, Katherine L. B.

2015-01-01

Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

A framework for assessing hydrogen management strategies involving multiple decisions

International Nuclear Information System (INIS)

Lee, S.D.; Suh, K.Y.; Park, G.C.; Jae, M.

2000-01-01

An accident management framework consisting of multiple and sequential decisions is developed and applied to a hydrogen control strategy for a reference plant. The compact influence diagrams including multiple decisions are constructed and evaluated with MAAP4 calculations. Each decision variable, represented by a node in the influence diagrams, has an uncertainty distribution. Using the values from the IPE (Individual Plant Examinations) report for the reference plant (UCN 3 and 4), the hydrogen control and accident management strategies are assessed. In this paper, a problem with two decisions is modeled for a simple illustration of the process involved. One decision is whether or not to actuate igniters at the time of core uncovery. Another decision is whether or not to turn on the containment sprays. We chose a small-break loss-of-coolant accident (LOCA) sequence, which was one of the dominant accident sequences in the reference plant. The framework involves the modeling of the decision problem by using decision-making tools, data analysis, and the MAAP4 calculations. It is shown that the proposed framework with a new measure for assessing hydrogen control is flexible enough to be applied to various accident management strategies. (author)

Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds.

Science.gov (United States)

Jaganathan, Ganesh K; Han, Yingying; Li, Weijie; Song, Danping; Song, Xiaoyan; Shen, Mengqi; Zhou, Qiang; Zhang, Chenxue; Liu, Baolin

2017-03-13

The physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h -1 ) suffered significantly higher membrane damage at temperature between -20 °C and -10 °C than slow cooled (3 °Ch -1 ) seeds (P  0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to -20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

Science.gov (United States)

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

The mechanisms involved at the cell level

International Nuclear Information System (INIS)

Leblanc, G.; Pourcher, Th.; Perron, B.; Guillain, F.; Quemeneur, E.; Fritsch, P.

2003-01-01

The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant?

Science.gov (United States)

Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-10-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia.

Investigations into the involvement of NMDA mechanisms in recognition memory.

Science.gov (United States)

Warburton, E Clea; Barker, Gareth R I; Brown, Malcom W

2013-11-01

This review will focus on evidence showing that NMDA receptor neurotransmission is critical for synaptic plasticity processes within brain regions known to be necessary for the formation of object recognition memories. The aim will be to provide evidence concerning NMDA mechanisms related to recognition memory processes and show that recognition memory for objects, places or associations between objects and places depends on NMDA neurotransmission within the perirhinal cortex, temporal association cortex medial prefrontal cortex and hippocampus. Administration of the NMDA antagonist AP5, selectively into each of these brain regions has revealed that the extent of the involvement NMDA receptors appears dependent on the type of information required to solve the recognition memory task; thus NMDA receptors in the perirhinal cortex are crucial for the encoding of long-term recognition memory for objects, and object-in-place associations, but not for short-term recognition memory or for retrieval. In contrast the hippocampus and medial prefrontal cortex are required for both long-term and short-term recognition memory for places or associations between objects and places, or for recognition memory tasks that have a temporal component. Such studies have therefore confirmed that the multiple brain regions make distinct contributions to recognition memory but in addition that more than one synaptic plasticity process must be involved. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

OpenAIRE

Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo

2015-01-01

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs ...

A case of disseminated hydatid disease by surgery involving multiple organs

Directory of Open Access Journals (Sweden)

Asli Tanrivermis Sayit

2014-09-01

Full Text Available Hydatid disease is the most common parasitic infection in the world, and is caused by the parasite Echinococcus granulosus. The most common site of this disease is the liver (75%, followed by the lungs, kidney, bones, and brain. Multiple abdominal organ and peritoneal involvement can also be seen in some cases. The dissemination of hydatid cyst disease can develop spontaneously or secondary to trauma or surgery. Here, we present the case of a 69-year-old man with multiple cyst hydatidosis, who underwent surgery for acute appendicitis approximately 20 years previously. Computed tomography of the abdomen shows the multiple active and inactive cystic lesions in the liver, spleen, right kidney, and mesentery. This patient required surgery several times, as well as medical treatment, after the rupture of a mesenteric hydatid cyst during the appendectomy. Combined anthelmintic treatment was recommended to the patient who refused further surgical treatment.

Mechanisms involved in the transport of mercuric ions in target tissues

Science.gov (United States)

Bridges, Christy C.; Zalups, Rudolfs K.

2016-01-01

Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells. PMID:27422290

Heterogeneity of reward mechanisms.

Science.gov (United States)

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

The multiple imputation method: a case study involving secondary data analysis.

Science.gov (United States)

Walani, Salimah R; Cleland, Charles M

2015-05-01

To illustrate with the example of a secondary data analysis study the use of the multiple imputation method to replace missing data. Most large public datasets have missing data, which need to be handled by researchers conducting secondary data analysis studies. Multiple imputation is a technique widely used to replace missing values while preserving the sample size and sampling variability of the data. The 2004 National Sample Survey of Registered Nurses. The authors created a model to impute missing values using the chained equation method. They used imputation diagnostics procedures and conducted regression analysis of imputed data to determine the differences between the log hourly wages of internationally educated and US-educated registered nurses. The authors used multiple imputation procedures to replace missing values in a large dataset with 29,059 observations. Five multiple imputed datasets were created. Imputation diagnostics using time series and density plots showed that imputation was successful. The authors also present an example of the use of multiple imputed datasets to conduct regression analysis to answer a substantive research question. Multiple imputation is a powerful technique for imputing missing values in large datasets while preserving the sample size and variance of the data. Even though the chained equation method involves complex statistical computations, recent innovations in software and computation have made it possible for researchers to conduct this technique on large datasets. The authors recommend nurse researchers use multiple imputation methods for handling missing data to improve the statistical power and external validity of their studies.

Primary bone lymphoma with multiple vertebral involvement

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Showkat Hussain Dar

2013-01-01

Full Text Available A 20-year-old student presented with 2 months history of fever and night sweats, 15 days history of low backache, progressive weakness of both limbs of 7 days duration, and urinary retention for last 24 h. Examination revealed a sensory level at D 10 dermatome and grade two power in both the lower limbs with absent reflexes. Examination of spine revealed a knuckle at T8 level, which was tender on palpation. MRI spine showed erosion of D11-12 and L1 in vertebral bodies with destruction of left pedicles, transverse processes and lamina, and a prominent psoas abscess. Post gadolinium study revealed ring-enhancing lesions in the D11-12 and L1 vertebrae as well as the dural sac. Fine needle aspiration cytology (FNAC and bone biopsy demonstrated a non-Hodgkin′s lymphoma (NHL, large cell high-grade of the spine (primary, which as per age is the youngest case of NHL ever reported in literature with multiple vertebral involvement.

Multiple mechanisms enable invasive species to suppress native species.

Science.gov (United States)

Bennett, Alison E; Thomsen, Meredith; Strauss, Sharon Y

2011-07-01

Invasive plants represent a significant threat to ecosystem biodiversity. To decrease the impacts of invasive species, a major scientific undertaking of the last few decades has been aimed at understanding the mechanisms that drive invasive plant success. Most studies and theories have focused on a single mechanism for predicting the success of invasive plants and therefore cannot provide insight as to the relative importance of multiple interactions in predicting invasive species' success. We examine four mechanisms that potentially contribute to the success of invasive velvetgrass Holcus lanatus: direct competition, indirect competition mediated by mammalian herbivores, interference competition via allelopathy, and indirect competition mediated by changes in the soil community. Using a combination of field and greenhouse approaches, we focus on the effects of H. lanatus on a common species in California coastal prairies, Erigeron glaucus, where the invasion is most intense. We found that H. lanatus had the strongest effects on E. glaucus via direct competition, but it also influenced the soil community in ways that feed back to negatively influence E. glaucus and other native species after H. lanatus removal. This approach provided evidence for multiple mechanisms contributing to negative effects of invasive species, and it identified when particular strategies were most likely to be important. These mechanisms can be applied to eradication of H. lanatus and conservation of California coastal prairie systems, and they illustrate the utility of an integrated set of experiments for determining the potential mechanisms of invasive species' success.

Plants-Derived Neuroprotective Agents: Cutting the Cycle of Cell Death through Multiple Mechanisms

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Taiwo Olayemi Elufioye

2017-01-01

Full Text Available Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs. The various NDs including Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features. Hence, several in vitro and in vivo study models specific to each disease have been employed to study NDs with the aim of understanding their underlying mechanisms and identifying new therapeutic strategies. Of the most prevalent drug development efforts employed in the past few decades, mechanisms implicated in the accumulation of protein-based deposits, oxidative stress, neuroinflammation, and certain neurotransmitter deficits such as acetylcholine and dopamine have been scrutinized in great detail. In this review, we presented classical examples of plant-derived neuroprotective agents by highlighting their structural class and specific mechanisms of action. Many of these natural products that have shown therapeutic efficacies appear to be working through the above-mentioned key multiple mechanisms of action.

Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

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Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

2017-10-01

Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

Natural Antioxidants: Multiple Mechanisms to Protect Skin From Solar Radiation

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Spencer Dunaway

2018-04-01

Full Text Available Human skin exposed to solar ultraviolet radiation (UVR results in a dramatic increase in the production of reactive oxygen species (ROS. The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs. Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application.

Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

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Kaur Punit

2008-11-01

Full Text Available Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Results Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. Conclusion The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells.

Science.gov (United States)

Urueña, Claudia; Cifuentes, Claudia; Castañeda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

2008-11-18

There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

Science.gov (United States)

Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

2000-05-01

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

2016-01-01

progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs

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Xue Fuzhong

2010-01-01

Full Text Available Abstract Background Genetic association study is currently the primary vehicle for identification and characterization of disease-predisposing variant(s which usually involves multiple single-nucleotide polymorphisms (SNPs available. However, SNP-wise association tests raise concerns over multiple testing. Haplotype-based methods have the advantage of being able to account for correlations between neighbouring SNPs, yet assuming Hardy-Weinberg equilibrium (HWE and potentially large number degrees of freedom can harm its statistical power and robustness. Approaches based on principal component analysis (PCA are preferable in this regard but their performance varies with methods of extracting principal components (PCs. Results PCA-based bootstrap confidence interval test (PCA-BCIT, which directly uses the PC scores to assess gene-disease association, was developed and evaluated for three ways of extracting PCs, i.e., cases only(CAES, controls only(COES and cases and controls combined(CES. Extraction of PCs with COES is preferred to that with CAES and CES. Performance of the test was examined via simulations as well as analyses on data of rheumatoid arthritis and heroin addiction, which maintains nominal level under null hypothesis and showed comparable performance with permutation test. Conclusions PCA-BCIT is a valid and powerful method for assessing gene-disease association involving multiple SNPs.

Multiple sclerosis : Mechanisms of myelin phagocytosis and lesion expansion

NARCIS (Netherlands)

Hendrickx, D.A.E.

2018-01-01

Multiple sclerosis (MS) is characterized by immune activation and focal demyelination in the central nervous system. The aim of this thesis was to gain more insight into the mechanisms of myelin phagocytosis by resident microglia and infiltrating macrophages. We first evaluated the expression of the

Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

International Nuclear Information System (INIS)

Burbery, N.J.; Das, R.; Ferguson, W.G.

2016-01-01

demonstrates an inherent link between the atomic structure and the thermal, energy and structure stability properties of grain boundaries; and reveals the mechanisms for GB-defect interactions involving localised GB structure transformation. - Highlights: • Influence of structural characteristics on vacancy emission from metastable Σ5 grain boundaries. • Nudged elastic band analysis of grain boundary structure transformation from vacancy absorption. • Effect of multiplicity on activation energy and mechanisms for vacancy and interstitial effects. • Structural analysis of dislocation nucleation process from nudged elastic band transition replicas. • Conceptual framework for defect-induced non equilibrium grain boundary structures.

Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

Energy Technology Data Exchange (ETDEWEB)

Burbery, N.J. [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Das, R., E-mail: r.das@auckland.ac.nz [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Ferguson, W.G. [Department of Chemical and Materials Engineering, University of Auckland, Auckland 1010 (New Zealand)

2016-08-15

demonstrates an inherent link between the atomic structure and the thermal, energy and structure stability properties of grain boundaries; and reveals the mechanisms for GB-defect interactions involving localised GB structure transformation. - Highlights: • Influence of structural characteristics on vacancy emission from metastable Σ5 grain boundaries. • Nudged elastic band analysis of grain boundary structure transformation from vacancy absorption. • Effect of multiplicity on activation energy and mechanisms for vacancy and interstitial effects. • Structural analysis of dislocation nucleation process from nudged elastic band transition replicas. • Conceptual framework for defect-induced non equilibrium grain boundary structures.

Central nervous system involvement in primary Sjogren`s syndrome manifesting as multiple sclerosis.

Science.gov (United States)

Liu, Jing-Yao; Zhao, Teng; Zhou, Chun-Kui

2014-04-01

Central nervous system symptoms in patients with primary Sjogren`s syndrome are rare. They can present as extraglandular manifestations and require a differential diagnosis from multiple sclerosis. Due to a variety of presentations, Sjogren`s syndrome with neurologic involvement may be difficult to diagnose. Here, we report a case of a 75-year-old woman who was first diagnosed with multiple sclerosis in 2010, but who was subsequently diagnosed with primary Sjogren`s syndrome 2 years later after showing signs of atypical neurologic manifestations. Therefore, primary Sjogren`s syndrome should be suspected in patients who present with atypical clinical and radiologic neurologic manifestations.

Flow Cytometry Method as a Diagnostic Tool for Pleural Fluid Involvement in a Patient with Multiple Myeloma

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Muzaffer Keklik

2012-10-01

Full Text Available Multiple myeloma is a malignant proliferation of plasma cells that mainly affects bone marrow. Pleural effusions secondary to pleural myelomatous involvement have rarely been reported in the literature. As it is rarely detected, we aimed to report a case in which pleural effusion of a multiple myeloma was confirmed as true myelomatous involvement by flow cytometry method. A 52-years old man presented to our clinic with chest and back pain lasting for 3 months. On the chest radiography, pleural fluid was detected in left hemithorax. Pleural fluid flow cytometry was performed. In the flow cytometry, CD56, CD38 and CD138 found to be positive, while CD19 was negative. True myelomatous pleural effusions are very uncommon, with fewer than 100 cases reported worldwide. Flow cytometry is a potentially useful diagnostic tool for clinical practice. We presented our case; as it has been rarely reported, although flow cytometer is a simple method for detection of pleural fluid involvement in multiple myeloma.

Collaboration Mechanism for Equipment Instruction of Multiple Energy Systems

Science.gov (United States)

Wang, Dong; Wang, Tuo; Wang, Qi; Zhang, Zhao; Zhao, Mingyu; Wang, Yinghui

2018-01-01

When multiple energy systems execute optimization instructions simultaneously, and the same equipment is Shared, the instruction conflict may occur. Aiming at the above problems, taking into account the control objectives of each system, the characteristics of different systems, such as comprehensive clean energy, energy efficiency, and peak filling, etc., designed the instruction coordination mechanism for the daemon. This mechanism mainly acts on the main station of the system, and form a final optimization instruction. For some specific scenarios, the collaboration mechanism of unlocking the terminal is supplemented. The mechanism determines the specific execution instructions based on the arrival time of the instruction. Finally, the experiment in Tianjin eco-city shows that this algorithm can meet the instruction and collaboration requirements of multi-energy systems, and ensure the safe operation of the equipment.

Multiple-shock initiation via statistical crack mechanics

Energy Technology Data Exchange (ETDEWEB)

Dienes, J.K.; Kershner, J.D.

1998-12-31

Statistical Crack Mechanics (SCRAM) is a theoretical approach to the behavior of brittle materials that accounts for the behavior of an ensemble of microcracks, including their opening, shear, growth, and coalescence. Mechanical parameters are based on measured strain-softening behavior. In applications to explosive and propellant sensitivity it is assumed that closed cracks act as hot spots, and that the heating due to interfacial friction initiates reactions which are modeled as one-dimensional heat flow with an Arrhenius source term, and computed in a subscale grid. Post-ignition behavior of hot spots is treated with the burn model of Ward, Son and Brewster. Numerical calculations using SCRAM-HYDROX are compared with the multiple-shock experiments of Mulford et al. in which the particle velocity in PBX 9501 is measured with embedded wires, and reactions are initiated and quenched.

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

DEFF Research Database (Denmark)

Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

2015-01-01

of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

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Tamas Kiss

Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

International Nuclear Information System (INIS)

Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

2010-01-01

Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

Energy Technology Data Exchange (ETDEWEB)

Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

2010-05-26

Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

Directory of Open Access Journals (Sweden)

Paola Massi

2010-05-01

Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

An Isolated Bee Sting Involving Multiple Cranial Nerves

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Hassan Motamed

2013-01-01

Full Text Available Hymenoptera stings are self-limiting events or due to allergic reactions. Sometimes envenomation with Hymenoptera can cause rare complications such as acute encephalopathy, peripheral neuritis, acute renal failure, nephrotic syndrome, silent myocardial infarction, rhabdomyolysis, conjunctivitis, corneal infiltration, lens subluxation, and optic neuropathy. The mechanism of peripheral nervous system damage is not clearly known. In our studied case after bee sting on face between the eyebrows with little erythema and  cm in size, bilateral blindness developed and gradually improved. Lateral movement of eyes was restricted with no pain. Involvement of cranial nerves including II, V, and VI was found. With conservative therapy after a year significant improvement has been achieved.

NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

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Haiwen Ni

Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

Multivertebral and epidural involvement of the multiple myeloma, as confirmed by magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Okuda, Yasuhiro; Tamaki, Norihiko; Hosoda, Koukichi; Ehara, Kazumasa; Matsumoto, Satoshi

1987-08-01

A case is reported of a multiple myeloma exhibiting symptoms of paraparesis as an initial manifestation following tetraparesis, but with no particular common symptoms of multiple myeloma. Laboratory findings, however, strongly suggested multiple myeloma, and this was confirmed by a biopsy. Radiological investigations could not show all the features of this tumor invasion, but revealed only the osteosclerotic and destructive changes in the cervical and thoracic spine, plus a complete block at the C2 level. Magnetic resonance imaging, however, disclosed entire lesions. There existed multiple vertebral involvements and an epidural invasion of the tumor, continuing to an extraspinal mass. Multiple myeloma is a disorder with varied manifestations; it is rarely present as a primary neuropathological entity. Among these manifestations, initial neurological manifestations in the form of peripheral neuropathy have been reported most commonly. Unusual clinical presentations such as in our case may result in an erroneous and delayed diagnosis unless an early and correct identification of the lesion is made. Magnetic resonance imaging is thought to be the most useful technique to detect such a multiple lesion in the spinal canal with no invasive manipulation.

Multiple-walled BN nanotubes obtained with a mechanical alloying technique

International Nuclear Information System (INIS)

Rosas, G.; Sistos, J.; Ascencio, J.A.; Medina, A.; Perez, R.

2005-01-01

An experimental method to obtain multiple-walled nanotubes of BN using low energy is presented. The method is based on the use of mechanical alloying techniques with elemental boron powders and nitrogen gas mixed in an autoclave at room temperature. The chemical and structural characteristics of the multiple-walled nanotubes were obtained using different techniques, such as X-ray diffraction, transmission electron microscopy, EELS microanalysis, high-resolution electron microscopy images and theoretical simulations based on the multisliced approach of the electron diffraction theory. This investigation clearly illustrates the production of multiple-wall BN nanotubes at room temperature. These results open up a new kind of synthesis method with low expense and important perspectives for use in large-quantity production. (orig.)

Authority inside the firm: multiple mechanisms of coordination

OpenAIRE

Bernard Baudry; Bruno Tinel

2004-01-01

In the last twenty years, through a growing awareness of contractual incompleteness, the concept of authority has regained primacy in the analysis of the employment relationship. This article pursues two goals. First, we assess the famous controversy between Coase and Alchian and Demsetz via an analysis of the foundations of intra-firm authority. Second, we argue that intra-firm authority cannot hinge on a single variable and, to the contrary, rests on multiple mechanisms. The employer's auth...

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

International Nuclear Information System (INIS)

Brenes, J.C.; Broiz, A.C.; Bassi, G.S.; Schwarting, R.K.W.; Brandão, M.L.

2012-01-01

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by Y -aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

Energy Technology Data Exchange (ETDEWEB)

Brenes, J.C. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Broiz, A.C.; Bassi, G.S. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Schwarting, R.K.W. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany); Brandão, M.L. [Instituto de Neurociências e Comportamento, Campus USP, Ribeirão Preto, SP (Brazil); Laboratório de Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2012-03-09

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by {sub Y}-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

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Borges, Juliana Pereira; Lessa, Marcos Adriano

2015-01-01

Background Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate. Objective To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury. Methods A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies. Results The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review. Conclusion On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions. PMID:25830711

Education on invasive mechanical ventilation involving intensive care nurses: a systematic review.

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Guilhermino, Michelle C; Inder, Kerry J; Sundin, Deborah

2018-03-26

Intensive care unit nurses are critical for managing mechanical ventilation. Continuing education is essential in building and maintaining nurses' knowledge and skills, potentially improving patient outcomes. The aim of this study was to determine whether continuing education programmes on invasive mechanical ventilation involving intensive care unit nurses are effective in improving patient outcomes. Five electronic databases were searched from 2001 to 2016 using keywords such as mechanical ventilation, nursing and education. Inclusion criteria were invasive mechanical ventilation continuing education programmes that involved nurses and measured patient outcomes. Primary outcomes were intensive care unit mortality and in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay, length of intubation, failed weaning trials, re-intubation incidence, ventilation-associated pneumonia rate and lung-protective ventilator strategies. Studies were excluded if they excluded nurses, patients were ventilated for less than 24 h, the education content focused on protocol implementation or oral care exclusively or the outcomes were participant satisfaction. Quality was assessed by two reviewers using an education intervention critical appraisal worksheet and a risk of bias assessment tool. Data were extracted independently by two reviewers and analysed narratively due to heterogeneity. Twelve studies met the inclusion criteria for full review: 11 pre- and post-intervention observational and 1 quasi-experimental design. Studies reported statistically significant reductions in hospital length of stay, length of intubation, ventilator-associated pneumonia rates, failed weaning trials and improvements in lung-protective ventilation compliance. Non-statistically significant results were reported for in-hospital and intensive care unit mortality, re-intubation and intensive care unit length of stay. Limited evidence of the effectiveness of

Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

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MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

2014-01-01

Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

Vascular aspects of multiple sclerosis

NARCIS (Netherlands)

D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques

Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial

Exploring Multiplication: Three-in-a-Row Lucky Numbers

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Russo, James A.

2018-01-01

Three-in-a-Row Lucky Numbers is an engaging, enjoyable, mathematically meaningful, game-based activity involving dice and a hundred chart, which can be used to introduce students to multiplication. The game provides a mechanism for students to explore the structure of multiplication, experiment with the distributive property, and begin to…

Direct and indirect stabilisation mechanisms in multiple electron capture

Energy Technology Data Exchange (ETDEWEB)

Roncin, P. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Barat, M. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Gaboriaud, M.N. [Paris-11 Univ., 91 -Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Szilagyi, Z.S. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires; Kazansky, A.K. [Paris-11 Univ., 91 - Orsay (France). Lab. de Collisions Atomiques et Moleculaires

1995-05-01

During the last years both experimental and theoretical works have focused on the problem of the stabilisation of two excited electrons on the projectile. In this contribution we would like to give experimental examples of the two suggested mechanisms and their extension to multiple electron capture. Our data are discussed together with those obtained with other experimental techniques and with theoretical predictions. (orig./WL).

Tuberous sclerosis: Ultrasound, CT and MRI features of two cases with multiple organ involvement

International Nuclear Information System (INIS)

Arslan, A.; Ciftci, E.; Cetin, A.; Selcuk, H.; Demirci, A.

1998-01-01

The cases of two patients with tuberous sclerosis with multiple sites of involvement are presented. Both patients had characteristic cerebral lesions of tuberous sclerosis associated with bilateral renal angiomyolipomas and hepatic hamartomas. Additionally there were diffuse pulmonary cystic changes in one patient and cardiac rhabdomyoma in the other. Copyright (1998) Blackwell Science Pty Ltd

Pulmonary Embolism as the First Manifestation of Multiple Myeloma

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N. Vallianou

2013-01-01

Full Text Available Multiple myeloma is considered a hypercoagulable state due to several mechanisms such as the increased IL-6 and immunoglobulins production, the defective fibrinolytic mechanism, and the acquired resistance to activated protein C that are involved in the pathogenesis and clinical futures of the disease. We describe a case of a female patient who presented to the hospital with pulmonary embolism as the first manifestation of the hypercoagulability of multiple myeloma.

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

Science.gov (United States)

Malysz, Jozef; Talamo, Giampaolo; Zhu, Junjia; Clarke, Loren E; Bayerl, Michael G; Ali, Liaqat; Helm, Klaus F; Chung, Catherine G

2016-05-01

Disease-specific skin lesions are rare in patients with multiple myeloma (MM). We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. We identified 13 patients with cutaneous lesions of MM. Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. The study group was relatively small. Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A mechanical characterisation on multiple timescales of electroconductive magnetorheological elastomers

Science.gov (United States)

Schümann, M.; Morich, J.; Kaufhold, T.; Böhm, V.; Zimmermann, K.; Odenbach, S.

2018-05-01

Magnetorheological elastomers are a type of smart hybrid material which combines elastic properties of a soft elastomer matrix with magnetic properties of magnetic micro particles. This leads to a material with magnetically controllable mechanical properties of which the magnetorheological effect is the best known. The addition of electroconductive particles to the polymer mix adds electrical properties to the material behaviour. The resulting electrical resistance of the sample can be manipulated by external magnetic fields and mechanical loads. This results in a distinct interplay of mechanical, electrical and magnetic effects with a highly complex time behaviour. In this paper a mechanical characterisation on multiple time scales was conducted to get an insight on the short and long-term electrical and mechanical behaviour of this novel material. The results show a complex resistivity behaviour on several timescales, sensitive to magnetic fields and strain velocity. The observed material exhibits fatigue and relaxation behaviour, whereas the magnetorheological effect appears not to interfere with the piezoresistive properties.

Flow Cytometry Method as a Diagnostic Tool for Pleural Fluid Involvement in a Patient with Multiple Myeloma

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MUZAFFER KEKLIK

2012-01-01

Full Text Available

Multiple myeloma is a malignant proliferation of plasma cells that mainly affects bone marrow. Pleural effusions secondary to pleural myelomatous involvement have rarely been reported in the literature. As it is rarely detected, we aimed to report a case in which pleural effusion of a multiple myeloma was confirmed as true myelomatous involvement by flow cytometry method. A 52-years old man presented to our clinic with chest and back pain lasting for 3 months. On the chest radiography, pleural fluid was detected in left hemithorax. Pleural fluid flow cytometry was performed. In the flow cytometry, CD56, CD38 and CD138 found to be positive, while CD19 was negative. True myelomatous pleural effusions are very uncommon, with fewer than 100 cases reported worldwide. Flow cytometry is a potentially useful diagnostic tool for clinical practice. We presented our case; as it has been rarely reported, although flow cytometer is a simple method for detection of pleural fluid involvement in multiple myeloma.

The usefulness of bone and bone-marrow scintigraphy in the detection of bone involvement in patients with multiple myeloma

International Nuclear Information System (INIS)

Otsuka, Nobuaki; Fukunaga, Masao; Sone, Teruki

1986-01-01

We used a combination of bone and bone-marrow scintigraphy to evaluate bone involvement in 15 patients with multiple myeloma (7 in untreated group and 8 in chemotherapy group). Of the 3 cases in untreated group whose 99m Tc-methylene diphosphonate (MDP) bone scans showed no abnormality, one had abnormal 99m Tc-suffer colloid bone-marrow scintigraphy. In other 4 cases of untreated group whose bone scan showed cold defects, bone-marrow scintigraphy delineated clearly the areas of tumor-cell invasion. On the other hand, in all chemotherapy cases, multiple hot spots were observed on bone scintigram, but on bone-marrow scintigram abnormalities were not recognized. In conclusion, the combination scintigraphy of bone and bone-marrow was a useful method in evluating bone involvement in patients with multiple myeloma. (author)

Motion laws synthesis for cam mechanisms with multiple follower displacement

Science.gov (United States)

Podgornyj, Yu I.; Skeeba, V. Yu; Kirillov, A. V.; Martynova, T. G.; Skeeba, P. Yu

2018-03-01

The research discusses the cam mechanisms design. The analysis of specialized literature indicates that the synthesis of the cam mechanisms laws of motion is currently done mainly by a standard set of acceleration curves. In some cases, the designer needs to synthesize a new acceleration law which should be task-specific and enforce a certain production step. The values of the technological loads and inertia forces loads generated by the mechanism are calculated to analyze the slay mechanism behavior in the production of closely woven fabrics. Mathematical packages MathCad and SolidWorks are used in calculations. As a result of the research, the authors propose the methodology for synthesizing the slay mechanism with multiple follower displacements for the point of contact between the reed and the fabric edge. Theoretical studies have been tested on a specific machine model (STB loom). The authors have synthesized the motion law of the filling threads beat-up mechanism for the production of strong fabrics. New basic and closing cam profiles are proposed. The results are designed to enhance the possibilities of the looms and to recommend the most efficient equipment operation modes for the producers.

Understanding the molecular mechanisms involved in the interfacial self-healing of supramolecular rubbers

NARCIS (Netherlands)

Bose, R.K.; Garcia Espallargas, S.J.; Van der Zwaag, S.

2013-01-01

Supramolecular rubbers based on 2-aminoethylimidazolidone and fatty acids with epoxy crosslinks have been shown to self-heal via multiple hydrogen bonding sites. In this work, several tools are used to investigate the molecular mechanisms taking place at the interface to understand cohesive healing

Estimation in a multiplicative mixed model involving a genetic relationship matrix

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Eccleston John A

2009-04-01

Full Text Available Abstract Genetic models partitioning additive and non-additive genetic effects for populations tested in replicated multi-environment trials (METs in a plant breeding program have recently been presented in the literature. For these data, the variance model involves the direct product of a large numerator relationship matrix A, and a complex structure for the genotype by environment interaction effects, generally of a factor analytic (FA form. With MET data, we expect a high correlation in genotype rankings between environments, leading to non-positive definite covariance matrices. Estimation methods for reduced rank models have been derived for the FA formulation with independent genotypes, and we employ these estimation methods for the more complex case involving the numerator relationship matrix. We examine the performance of differing genetic models for MET data with an embedded pedigree structure, and consider the magnitude of the non-additive variance. The capacity of existing software packages to fit these complex models is largely due to the use of the sparse matrix methodology and the average information algorithm. Here, we present an extension to the standard formulation necessary for estimation with a factor analytic structure across multiple environments.

Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

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M. Saliani

2016-01-01

Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

Science.gov (United States)

Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

2012-07-01

Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Linking neuroscientific research on decision making to the educational context of novice students assigned to a multiple-choice scientific task involving common misconceptions about electrical circuits

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Patrice ePotvin

2014-01-01

Full Text Available Functional magnetic resonance imaging was used to identify the brain-based mechanisms of uncertainty and certainty associated with answers to multiple-choice questions involving common misconceptions about electric circuits. Twenty-two (22 scientifically novice participants (humanities and arts college students were asked, in an fMRI study, whether or not they thought the light bulbs in images presenting electric circuits were lighted up correctly, and if they were certain or uncertain of their answers. When participants reported that they were unsure of their responses, analyses revealed significant activations in brain areas typically involved in uncertainty (anterior cingulate cortex, anterior insula cortex, and superior/dorsomedial frontal cortex and in the left middle/superior temporal lobe. Certainty was associated with large bilateral activations in the occipital and parietal regions usually involved in visuospatial processing. Correct-and-certain answers were associated with activations that suggest a stronger mobilization of visual attention resources when compared to incorrect-and-certain answers. These findings provide insights into brain-based mechanisms of uncertainty that are activated when common misconceptions, identified as such by science education research literature, interfere in decision making in a school-like task. We also discuss the implications of these results from an educational perspective.

Neurobiological mechanisms involved in sleep bruxism.

Science.gov (United States)

Lavigne, G J; Kato, T; Kolta, A; Sessle, B J

2003-01-01

Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

[Disease concept, etiology and mechanisms of multiple sclerosis].

Science.gov (United States)

Kira, Jun-Ichi

2014-11-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

Multiple vascular anomalies involving renal, testicular and suprarenal arteries

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Suresh Rao

2015-09-01

Full Text Available Knowledge of variations of blood vessels of the abdomen is important during operative, diagnostic and endovascular pro- cedures. During routine dissection of the abdominal cavity, we came across multiple vascular anomalies involving renal, suprarenal and testicular arteries. The left kidney was supplied by two renal arteries originating together from the abdomi- nal aorta, and the right kidney was supplied by two accessory renal arteries, one of which was arising from the right renal artery and the other one from the aorta (about 2 inches below the origin of the renal artery. Accessory renal veins were present on both sides. The right testicular artery was arising from the lower accessory renal artery. The left testicular artery was looping around the inferior tributary of the left renal vein, whereby forming a sharp kink. The left middle suprarenal artery was diving into three small branches; the upper two branches were supplying the left suprarenal gland, whereas the lower branch was supplying the left kidney. Furthermore, detailed literature and the clinical and surgical importance of the case are discussed. [Arch Clin Exp Surg 2015; 4(3.000: 168-171

Statistics, synergy, and mechanism of multiple photogeneration of excitons in quantum dots: Fundamental and applied aspects

International Nuclear Information System (INIS)

Oksengendler, B. L.; Turaeva, N. N.; Uralov, I.; Marasulov, M. B.

2012-01-01

The effect of multiple exciton generation is analyzed based on statistical physics, quantum mechanics, and synergetics. Statistical problems of the effect of multiple exciton generation (MEG) are broadened and take into account not only exciton generation, but also background excitation. The study of the role of surface states of quantum dots is based on the synergy of self-catalyzed electronic reactions. An analysis of the MEG mechanism is based on the idea of electronic shaking using the sudden perturbation method in quantum mechanics. All of the above-mentioned results are applied to the problem of calculating the limiting efficiency to transform solar energy into electric energy. (authors)

Multiple kinase pathways involved in the different de novo sensitivity of pancreatic cancer cell lines to 17-AAG.

Science.gov (United States)

Liu, Heping; Zhang, Ti; Chen, Rong; McConkey, David J; Ward, John F; Curley, Steven A

2012-07-01

17-Allylamino-17-demethoxygeldanamycin (17-AAG) specifically targets heat shock protein (HSP)90 and inhibits its chaperoning functions for multiple kinases involved in cancer cell growth and survival. To select responsive patients, the molecular mechanisms underlying the sensitivity of cancer cells to 17-AAG must be elucidated. We used cytotoxicity assays and Western blotting to explore the effects of 17-AAG and sorafenib on cell survival and expression of multiple kinases in the pancreatic cancer cell lines AsPC-1 and Panc-1. Gene cloning and transfection, siRNA silencing, and immunohistochemistry were used to evaluate the effects of mutant p53 protein on 17-AAG sensitivity. AsPC-1 and Panc-1 responded differently to 17-AAG, with half maximal inhibitory concentration (IC(50)) values of 0.12 and 3.18 μM, respectively. Comparable expression of HSP90, HSP70, and HSP27 was induced by 17-AAG in AsPC-1 and Panc-1 cells. P-glycoprotein and mutant p53 did not affect 17-AAG sensitivity in these cell lines. Multiple kinases are more sensitive to HSP90 inhibition in AsPC-1 than in Panc-1 cells. After 17-AAG treatment, p-Bad (S112) decreased in AsPC-1 cells and increased in Panc-1 cells. Sorafenib markedly increased p-Akt, p-ERK1/2, p-GSK-3β, and p-S6 in both cell lines. Accordingly, 17-AAG and sorafenib acted antagonistically in AsPC-1 and Panc-1 cells, except at high concentrations in AsPC-1 cells. Differential inhibition of multiple kinases is responsible for the different de novo sensitivity of AsPC-1 and Panc-1 cells to HSP90 inhibition. P-glycoprotein and mutant p53 protein did not play a role in the sensitivity of pancreatic cancer cells to 17-AAG. Copyright © 2012 Elsevier Inc. All rights reserved.

An ENA ATPase, MaENA1, of Metarhizium acridum influences the Na(+)-, thermo- and UV-tolerances of conidia and is involved in multiple mechanisms of stress tolerance.

Science.gov (United States)

Ma, Qinsi; Jin, Kai; Peng, Guoxiong; Xia, Yuxian

2015-10-01

In fungi, ENA ATPases play key roles in osmotic and alkaline pH tolerance, although their functions in thermo- and UV-tolerances have not been explored. Entomopathogenic fungi are naturally widespread and have considerable potential in pest control. An ENA ATPase gene, MaENA1, from the entomopathogenic fungus Metarhizium acridum was functionally analyzed by deletion. MaENA1-disruption strain (ΔMaENA1) was less tolerant to NaCl, heat, and UV radiation than a wild-type strain (WT). Digital Gene Expression profiling of conidial RNAs resulted in 281 differentially expressed genes (DEGs) between the WT and ΔMaENA1 strains. Eighty-five DEGs, 56 of which were down-regulated in the ΔMaENA1 strain, were shown to be associated with heat/UV tolerance, including six cytochrome P450 superfamily genes, 35 oxidoreductase genes, 24 ion-binding genes, seven DNA repair genes, and five other genes. In addition, eight genes were components of stress responsive pathways, including the Ras-cAMP PKA pathway, the RIM101 pathway, the Ca(2+)/calmodulin pathway, the TOR pathway, and the HOG/Spc1/Sty1/JNK pathway. These results demonstrated that MaENA1 influences fungal tolerances to Na(+), heat, and UV radiation in M. acridum, and is involved in multiple mechanisms of stress tolerance. Therefore, MaENA1 is required for the adaptation and survival of entomopathogenic fungi in stressful conditions in the environment and in their hosts. Copyright © 2015 Elsevier Inc. All rights reserved.

Pioneering partnerships: Resident involvement from multiple perspectives

NARCIS (Netherlands)

Baur, V.E.; Abma, T.A.; Boelsma, F.; Woelders, S.

2013-01-01

Resident involvement in residential care homes is a challenge due to shortcomings of consumerist and formal approaches such as resident councils. The PARTNER approach aims to involve residents through collective action to improve their community life and wellbeing. The purpose of this article is to

A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α

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Dickinson Bryony A

2009-06-01

Full Text Available Abstract Background Long-term depression (LTD in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs and muscarinic acethycholine receptors (mAChRs. Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC, it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α. Results Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms. Conclusion Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.

Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

Science.gov (United States)

Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

2012-08-01

Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

Quantum-Mechanical Calculations on Molecular Substructures Involved in Nanosystems

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Beata Szefler

2014-09-01

Full Text Available In this review article, four ideas are discussed: (a aromaticity of fullerenes patched with flowers of 6-and 8-membered rings, optimized at the HF and DFT levels of theory, in terms of HOMA and NICS criteria; (b polybenzene networks, from construction to energetic and vibrational spectra computations; (c quantum-mechanical calculations on the repeat units of various P-type crystal networks and (d construction and stability evaluation, at DFTB level of theory, of some exotic allotropes of diamond D5, involved in hyper-graphenes. The overall conclusion was that several of the yet hypothetical molecular nanostructures herein described are serious candidates to the status of real molecules.

Multiple Scattering in Random Mechanical Systems and Diffusion Approximation

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Feres, Renato; Ng, Jasmine; Zhang, Hong-Kun

2013-10-01

This paper is concerned with stochastic processes that model multiple (or iterated) scattering in classical mechanical systems of billiard type, defined below. From a given (deterministic) system of billiard type, a random process with transition probabilities operator P is introduced by assuming that some of the dynamical variables are random with prescribed probability distributions. Of particular interest are systems with weak scattering, which are associated to parametric families of operators P h , depending on a geometric or mechanical parameter h, that approaches the identity as h goes to 0. It is shown that ( P h - I)/ h converges for small h to a second order elliptic differential operator on compactly supported functions and that the Markov chain process associated to P h converges to a diffusion with infinitesimal generator . Both P h and are self-adjoint (densely) defined on the space of square-integrable functions over the (lower) half-space in , where η is a stationary measure. This measure's density is either (post-collision) Maxwell-Boltzmann distribution or Knudsen cosine law, and the random processes with infinitesimal generator respectively correspond to what we call MB diffusion and (generalized) Legendre diffusion. Concrete examples of simple mechanical systems are given and illustrated by numerically simulating the random processes.

Multiple bilateral lower limb fractures in a 2-year-old child: previously unreported injury with a unique mechanism

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Anuj Jain

2014-10-01

Full Text Available 【Abstract】Fall from height is a common cause of unintentional injuries in children and accounts for 6% of all trauma-related childhood deaths, usually from head injury. We report a case of a 2-year-old child with multiple fractures of the bilateral lower limbs due to this reason. A child fell from a height of around 15 feet after toppling from a alcony. He developed multiple fractures involving the right femoral shaft, right distal femoral epiphysis (Salter Harris type 2, right distal metaphysis of the tibia and fi bula, and undisplaced Salter Harris type 2 epiphyseal injury of the left distal tibia. There were no head, abdominal or spinal injuries. The patient was taken into emergency operation theatre after initial management which consisted of intravenous fl uids, blood transfusion, and splintage of both lower limbs. Fracture of the femoral shaft was treated by closed reduction and fixation using two titanium elastic nails. Distal femoral physeal injury required open eduction and fixation with K wires. Distal tibia fractures were closely reduced and managed nonoperatively in both the lower limbs. All the fractures united in four weeks. At the last follow-up, the child had no disability and was able to perform daily ctivities comfortably. We also proposed the unique mechanism of injury in this report. Key words: Multiple bilateral lower limb fractures; Fall; Child

Multiple-event probability in general-relativistic quantum mechanics. II. A discrete model

International Nuclear Information System (INIS)

Mondragon, Mauricio; Perez, Alejandro; Rovelli, Carlo

2007-01-01

We introduce a simple quantum mechanical model in which time and space are discrete and periodic. These features avoid the complications related to continuous-spectrum operators and infinite-norm states. The model provides a tool for discussing the probabilistic interpretation of generally covariant quantum systems, without the confusion generated by spurious infinities. We use the model to illustrate the formalism of general-relativistic quantum mechanics, and to test the definition of multiple-event probability introduced in a companion paper [Phys. Rev. D 75, 084033 (2007)]. We consider a version of the model with unitary time evolution and a version without unitary time evolution

The application of the linear-quadratic model to fractionated radiotherapy when there is incomplete normal tissue recovery between fractions, and possible implications for treatments involving multiple fractions per day

International Nuclear Information System (INIS)

Dale, R.G.

1986-01-01

By extending a previously developed mathematical model based on the linear-quadratic dose-effect relationship, it is possible to examine the consequences of performing fractionated treatments for which there is insufficient time between fractions to allow complete damage repair. Equations are derived which give the relative effectiveness of such treatments in terms of tissue-repair constants (μ values) and α/β ratios, and these are then applied to some examples of treatments involving multiple fractions per day. The interplay of the various mechanisms involved (including repopulation effects) and their possible influence on treatments involving closely spaced fractions are examined. If current indications of the differences in recovery rates between early- and late-reacting normal tissues are representative, then it is shown that such differences may limit the clinical potential of accelerated fractionation regimes, where several fractions per day are given in a relatively short overall time. (author)

Molecular mechanisms of HIV-1 associated neurodegeneration

Indian Academy of Sciences (India)

Unknown

progressive multiple symptoms of motor, cognitive dys- function and behavioural ..... using different types of neurons such as rodent cortical, hippocampal and ..... in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor ...

Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

International Nuclear Information System (INIS)

Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico; Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio; Russo, Camilla; Feriozzi, Sandro; Veroux, Massimiliano; Battaglia, Yuri; Concolino, Daniela; Pieruzzi, Federico; Tuttolomondo, Antonino; Caronia, Aurelio; Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo

2017-01-01

Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

Energy Technology Data Exchange (ETDEWEB)

Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

2017-06-15

Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

Science.gov (United States)

Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

Involvement of Multiple Transporters-mediated Transports in Mizoribine and Methotrexate Pharmacokinetics

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Teruo Murakami

2012-08-01

Full Text Available Mizoribine is administered orally and excreted into urine without being metabolized. Many research groups have reported a linear relationship between the dose and peak serum concentration, between the dose and AUC, and between AUC and cumulative urinary excretion of mizoribine. In contrast, a significant interindividual variability, with a small intraindividual variability, in oral bioavailability of mizoribine is also reported. The interindividual variability is mostly considered to be due to the polymophisms of transporter genes. Methotrexate (MTX is administered orally and/or by parenteral routes, depending on the dose. Metabolic enzymes and multiple transporters are involved in the pharmacokinetics of MTX. The oral bioavailability of MTX exhibits a marked interindividual variability and saturation with increase in the dose of MTX, with a small intraindividual variability, where the contribution of gene polymophisms of transporters and enzymes is suggested. Therapeutic drug monitoring of both mizoribine and MTX is expected to improve their clinical efficacy in the treatment of rheumatoid arthritis.

Multiple Study of Case Involving Implementation of Lean Manufacturing

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Delvio Venanzi

2018-03-01

Full Text Available This article aims to show some factors that can cause companies to succeed or fail in their attempts to use lean manufacturing, by performing a multiple case study which presents two successful cases and three conditions of failure, in a survey of five large companies, all belonging to the metal-mechanical sector, located in Campinas and Sorocaba, both in the state of São Paulo, Brazil. The data were collected using exploratory research between the periods of January 2013 and February 2015. The results show that successful cases of lean manufacturing implementation are the result of a more organized work environment, standardization of production and service areas, employee satisfaction, productivity results and quality of the final product. Unsuccessful deployments result from poor execution and faulty planning, that has no benefit and ultimately decrease the morale of its employees, creating more distrust and frustration directly influencing the results and productivity. In other words, lean manufacturing implementation requires hard and continuous work and these procedures should be aligned with the mission and goals of companies and mainly focus on the maintenance result by using tools to monitor and track the process systematically and also making investments to eliminate waste.

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method.

Science.gov (United States)

König, Gerhard; Mei, Ye; Pickard, Frank C; Simmonett, Andrew C; Miller, Benjamin T; Herbert, John M; Woodcock, H Lee; Brooks, Bernard R; Shao, Yihan

2016-01-12

A recently developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for 12 small molecules. First, free energy simulations are performed with a classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, and then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10-0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

Color vision versus pattern visual evoked potentials in the assessment of subclinical optic pathway involvement in multiple sclerosis

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Fatih C Gundogan

2013-01-01

Full Text Available Background: Optic pathway involvement in multiple sclerosis is frequently the initial sign in the disease process. In most clinical applications, pattern visual evoked potential (PVEP is used in the assessment of optic pathway involvement. Objective: To question the value of PVEP against color vision assessment in the diagnosis of subclinical optic pathway involvement. Materials and Methods: This prospective, cross-sectional study included 20 multiple sclerosis patients without a history of optic neuritis, and 20 healthy control subjects. Farnsworth-Munsell (FM 100-Hue testing and PVEPs to 60-min arc and 15-min arc checks by using Roland-Consult RetiScan® system were performed. P 100 amplitude, P 100 latency in PVEP and total error scores (TES in FM 100-Hue test were assessed. Results: Expanded Disability Status Scale score and the time from diagnosis were 2.21 ± 2.53 (ranging from 0 to 7 and 4.1 ± 4.4 years. MS group showed significantly delayed P 100 latency for both checks (P 0.05 for all. 14 MS patients (70% had an increased TESs in FM-100 Hue, 11 (55% MS patients had delayed P 100 latency and 9 (45% had reduced P 100 amplitude. The areas under the ROC curves were 0.944 for FM-100 Hue test, 0.753 for P 100 latency, and 0.173 for P 100 amplitude. Conclusions: Color vision testing seems to be more sensitive than PVEP in detecting subclinical visual pathway involvement in MS.

Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth.

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Commandeur, Arno E; Styer, Aaron K; Teixeira, Jose M

2015-01-01

Uterine leiomyomas (fibroids) are highly prevalent benign smooth muscle tumors of the uterus. In the USA, the lifetime risk for women developing uterine leiomyomas is estimated as up to 75%. Except for hysterectomy, most therapies or treatments often provide only partial or temporary relief and are not successful in every patient. There is a clear racial disparity in the disease; African-American women are estimated to be three times more likely to develop uterine leiomyomas and generally develop more severe symptoms. There is also familial clustering between first-degree relatives and twins, and multiple inherited syndromes in which fibroid development occurs. Leiomyomas have been described as clonal and hormonally regulated, but despite the healthcare burden imposed by the disease, the etiology of uterine leiomyomas remains largely unknown. The mechanisms involved in their growth are also essentially unknown, which has contributed to the slow progress in development of effective treatment options. A comprehensive PubMed search for and critical assessment of articles related to the epidemiological, biological and genetic clues for uterine leiomyoma development was performed. The individual functions of some of the best candidate genes are explained to provide more insight into their biological function and to interconnect and organize genes and pathways in one overarching figure that represents the current state of knowledge about uterine leiomyoma development and growth. In this review, the widely recognized roles of estrogen and progesterone in uterine leiomyoma pathobiology on the basis of clinical and experimental data are presented. This is followed by fundamental aspects and concepts including the possible cellular origin of uterine fibroids. The central themes in the subsequent parts are cytogenetic aberrations in leiomyomas and the racial/ethnic disparities in uterine fibroid biology. Then, the attributes of various in vitro and in vivo, human syndrome

[Current description of multiple sclerosis].

Science.gov (United States)

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

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Georgios Koutsis

2015-01-01

Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

Science.gov (United States)

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

Service user involvement enhanced the research quality in a study using interpretative phenomenological analysis - the power of multiple perspectives.

Science.gov (United States)

Mjøsund, Nina Helen; Eriksson, Monica; Espnes, Geir Arild; Haaland-Øverby, Mette; Jensen, Sven Liang; Norheim, Irene; Kjus, Solveig Helene Høymork; Portaasen, Inger-Lill; Vinje, Hege Forbech

2017-01-01

The aim of this study was to examine how service user involvement can contribute to the development of interpretative phenomenological analysis methodology and enhance research quality. Interpretative phenomenological analysis is a qualitative methodology used in nursing research internationally to understand human experiences that are essential to the participants. Service user involvement is requested in nursing research. We share experiences from 4 years of collaboration (2012-2015) on a mental health promotion project, which involved an advisory team. Five research advisors either with a diagnosis or related to a person with severe mental illness constituted the team. They collaborated with the research fellow throughout the entire research process and have co-authored this article. We examined the joint process of analysing the empirical data from interviews. Our analytical discussions were audiotaped, transcribed and subsequently interpreted following the guidelines for good qualitative analysis in interpretative phenomenological analysis studies. The advisory team became 'the researcher's helping hand'. Multiple perspectives influenced the qualitative analysis, which gave more insightful interpretations of nuances, complexity, richness or ambiguity in the interviewed participants' accounts. The outcome of the service user involvement was increased breadth and depth in findings. Service user involvement improved the research quality in a nursing research project on mental health promotion. The interpretative element of interpretative phenomenological analysis was enhanced by the emergence of multiple perspectives in the qualitative analysis of the empirical data. We argue that service user involvement and interpretative phenomenological analysis methodology can mutually reinforce each other and strengthen qualitative methodology. © 2016 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

Modified random hinge transport mechanics and multiple scattering step-size selection in EGS5

International Nuclear Information System (INIS)

Wilderman, S.J.; Bielajew, A.F.

2005-01-01

The new transport mechanics in EGS5 allows for significantly longer electron transport step sizes and hence shorter computation times than required for identical problems in EGS4. But as with all Monte Carlo electron transport algorithms, certain classes of problems exhibit step-size dependencies even when operating within recommended ranges, sometimes making selection of step-sizes a daunting task for novice users. Further contributing to this problem, because of the decoupling of multiple scattering and continuous energy loss in the dual random hinge transport mechanics of EGS5, there are two independent step sizes in EGS5, one for multiple scattering and one for continuous energy loss, each of which influences speed and accuracy in a different manner. Further, whereas EGS4 used a single value of fractional energy loss (ESTEPE) to determine step sizes at all energies, to increase performance by decreasing the amount of effort expended simulating lower energy particles, EGS5 permits the fractional energy loss values which are used to determine both the multiple scattering and continuous energy loss step sizes to vary with energy. This results in requiring the user to specify four fractional energy loss values when optimizing computations for speed. Thus, in order to simplify step-size selection and to mitigate step-size dependencies, a method has been devised to automatically optimize step-size selection based on a single material dependent input related to the size of problem tally region. In this paper we discuss the new transport mechanics in EGS5 and describe the automatic step-size optimization algorithm. (author)

Development of Physics and Control of Multiple Forcing Mechanisms for the Alaska Tsunami Forecast Model

Science.gov (United States)

Bahng, B.; Whitmore, P.; Macpherson, K. A.; Knight, W. R.

2016-12-01

The Alaska Tsunami Forecast Model (ATFM) is a numerical model used to forecast propagation and inundation of tsunamis generated by earthquakes or other mechanisms in either the Pacific Ocean, Atlantic Ocean or Gulf of Mexico. At the U.S. National Tsunami Warning Center (NTWC), the use of the model has been mainly for tsunami pre-computation due to earthquakes. That is, results for hundreds of hypothetical events are computed before alerts, and are accessed and calibrated with observations during tsunamis to immediately produce forecasts. The model has also been used for tsunami hindcasting due to submarine landslides and due to atmospheric pressure jumps, but in a very case-specific and somewhat limited manner. ATFM uses the non-linear, depth-averaged, shallow-water equations of motion with multiply nested grids in two-way communications between domains of each parent-child pair as waves approach coastal waters. The shallow-water wave physics is readily applicable to all of the above tsunamis as well as to tides. Recently, the model has been expanded to include multiple forcing mechanisms in a systematic fashion, and to enhance the model physics for non-earthquake events.ATFM is now able to handle multiple source mechanisms, either individually or jointly, which include earthquake, submarine landslide, meteo-tsunami and tidal forcing. As for earthquakes, the source can be a single unit source or multiple, interacting source blocks. Horizontal slip contribution can be added to the sea-floor displacement. The model now includes submarine landslide physics, modeling the source either as a rigid slump, or as a viscous fluid. Additional shallow-water physics have been implemented for the viscous submarine landslides. With rigid slumping, any trajectory can be followed. As for meteo-tsunami, the forcing mechanism is capable of following any trajectory shape. Wind stress physics has also been implemented for the meteo-tsunami case, if required. As an example of multiple

Multiple scattering in the nuclear rearrangement reactions at medium energy

International Nuclear Information System (INIS)

Tekou, A.

1980-09-01

It is shown that the multiple scattering mechanism is very important in the transfer of the large momenta involved in the nuclear rearrangement reactions at medium energy. In contrast to the usual belief, the reaction cross-section is not very sensitive to the high momenta components of the nuclear wave function. The multiple scattering mechanism is especially important in 4 He(p,d) 3 He reaction around 800 MeV. Here the collisions involving two nucleons of the target nucleus are dominant. The triple collisions contribution is also important. The four collision contribution is negligible in the forward direction and sizeable at large angles. Thus, using the K.M.T. approach in DWBA calculations, the second order term of the optical potential must be included. So, is it not well established that the second term of the K.M.T. optical potential is important for the proton elastic scattering on light nuclei. (author)

Absorption of Carotenoids and Mechanisms Involved in Their Health-Related Properties.

Science.gov (United States)

Cervantes-Paz, Braulio; Victoria-Campos, Claudia I; Ornelas-Paz, José de Jesús

Carotenoids participate in the normal metabolism and function of the human body. They are involved in the prevention of several diseases, especially those related to the inflammation syndrome. Their main mechanisms of action are associated to their potent antioxidant activity and capacity to regulate the expression of specific genes and proteins. Recent findings suggest that carotenoid metabolites may explain several processes where the participation of their parent carotenoids was unclear. The health benefits of carotenoids strongly depend on their absorption and transformation during gastrointestinal digestion. The estimation of the 'bioaccessibility' of carotenoids through in vitro models have made possible the evaluation of the effect of a large number of factors on key stages of carotenoid digestion and intestinal absorption. The bioaccessibility of these compounds allows us to have a clear idea of their potential bioavailability, a term that implicitly involves the biological activity of these compounds.

Mechanisms involved in metformin action in the treatment of polycystic ovary syndrome.

Science.gov (United States)

Motta, A B

2009-01-01

The N, N' dimethyl-biguanide : Metformin is an antidiabetic drug that increases glucose utilization in insulin-sensitive tissues. As Polycystic Ovary Syndrome (PCOS) and diabetes share some altered parameters-such as abnormal glucose: insulin ratio, altered lipidic metabolism and insulin-resistance syndrome- the use of metformin has become increasingly accepted and widespread in the treatment of PCOS. Currently, metformin is used to induce ovulation and during early pregnancy in PCOS patients, however, a complete knowledge of the metformin action has not been achieved yet. This review describes beyond the classical reproductive action of metformin and explores other benefits of the drug. In addition, the present work discusses the molecular mechanisms involved further than the classical pathway that involves the AMP-activated protein kinase.

Microstructural response and grain refinement mechanism of commercially pure titanium subjected to multiple laser shock peening impacts

International Nuclear Information System (INIS)

Lu, J.Z.; Wu, L.J.; Sun, G.F.; Luo, K.Y.; Zhang, Y.K.; Cai, J.; Cui, C.Y.; Luo, X.M.

2017-01-01

The microstructural response and grain subdivision process in commercially pure (CP) titanium subjected to multiple laser shock peening (LSP) impacts were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The micro-hardness curves as a function of the impact time were also determined. The deformation-induced grain refinement mechanism of the close-packed hexagonal (hcp) material by laser shock wave was subsequently analyzed. Experimental results showed that uniform equiaxed grains with an average size of less than 50 nm were generated due to the ultra-high plastic strain induced by multiple LSP impacts. Special attention was paid to four types of novel deformation-induced microstructural features, including a layered slip band in the tension deformation zone, and inverse-transformation martensite, micro-twin grating and micro-twin collision in the compression deformation zone. Furthermore, the grain refinement mechanism in the near-surface layer of CP titanium subjected to multiple LSP impacts contains two types of simultaneous subdivision modes: multi-directional mechanical twin (MT)-MT intersections at (sub)micrometer scale, and the intersection between longitudinal secondary MTs and transverse dislocation walls at nanometer scale. In addition, both grain refinement (nanocrystallization) and the existence of a small amount of inverse-transformation martensite induced by multiple LSP impacts contribute to an increase in the micro-hardness of the near-surface layer.

Clustering mechanism of oxocarboxylic acids involving hydration reaction: Implications for the atmospheric models

Science.gov (United States)

Liu, Ling; Kupiainen-Määttä, Oona; Zhang, Haijie; Li, Hao; Zhong, Jie; Kurtén, Theo; Vehkamäki, Hanna; Zhang, Shaowen; Zhang, Yunhong; Ge, Maofa; Zhang, Xiuhui; Li, Zesheng

2018-06-01

The formation of atmospheric aerosol particles from condensable gases is a dominant source of particulate matter in the boundary layer, but the mechanism is still ambiguous. During the clustering process, precursors with different reactivities can induce various chemical reactions in addition to the formation of hydrogen bonds. However, the clustering mechanism involving chemical reactions is rarely considered in most of the nucleation process models. Oxocarboxylic acids are common compositions of secondary organic aerosol, but the role of oxocarboxylic acids in secondary organic aerosol formation is still not fully understood. In this paper, glyoxylic acid, the simplest and the most abundant atmospheric oxocarboxylic acid, has been selected as a representative example of oxocarboxylic acids in order to study the clustering mechanism involving hydration reactions using density functional theory combined with the Atmospheric Clusters Dynamic Code. The hydration reaction of glyoxylic acid can occur either in the gas phase or during the clustering process. Under atmospheric conditions, the total conversion ratio of glyoxylic acid to its hydration reaction product (2,2-dihydroxyacetic acid) in both gas phase and clusters can be up to 85%, and the product can further participate in the clustering process. The differences in cluster structures and properties induced by the hydration reaction lead to significant differences in cluster formation rates and pathways at relatively low temperatures.

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

OpenAIRE

Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

2017-01-01

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

Functional Neuroanatomy Involved in Automatic order Mental Arithmetic and Recitation of the Multiplication Table

Science.gov (United States)

Wang, Li-Qun; Saito, Masao

We used 1.5T functional magnetic resonance imaging (fMRI) to explore that which brain areas contribute uniquely to numeric computation. The BOLD effect activation pattern of metal arithmetic task (successive subtraction: actual calculation task) was compared with multiplication tables repetition task (rote verbal arithmetic memory task) response. The activation found in right parietal lobule during metal arithmetic task suggested that quantitative cognition or numeric computation may need the assistance of sensuous convert, such as spatial imagination and spatial sensuous convert. In addition, this mechanism may be an ’analog algorithm’ in the simple mental arithmetic processing.

Mechanical property changes during neonatal development and healing using a multiple regression model.

Science.gov (United States)

Ansorge, Heather L; Adams, Sheila; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2012-04-30

During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but a mechanically inferior tendon is produced. As a result, developmental processes have been postulated as a potential paradigm for elucidation of mechanistic insight required to develop treatment modalities to improve adult tissue healing. The objective of this study was to compare and contrast normal development with injury during early and late developmental healing. Using backwards multiple linear regressions, quantitative and objective information was obtained into the structure-function relationships in tendon. Specifically, proteoglycans were shown to be significant predictors of modulus during early developmental healing but not during late developmental healing or normal development. Multiple independent parameters predicted percent relaxation during normal development, however, only biglycan and fibril diameter parameters predicted percent relaxation during early developmental healing. Lastly, multiple differential predictors were observed between early development and early developmental healing; however, no differential predictors were observed between late development and late developmental healing. This study presents a model through which objective analysis of how compositional and structural parameters that affect the development of mechanical parameters can be quantitatively measured. In addition, information from this study can be used to develop new treatment and therapies through which improved adult tendon healing can be obtained. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lean Customer Involvement : A Multiple Case Study on the Effects of Kanban on Customer Involvement

OpenAIRE

Lundheim, Henning

2012-01-01

Customer involvement is an important, but challenging part of software development. Delays and failures can often be attributed to a lack of customer involvement. Different development methodologies provide different strategies for customer involvement, all with their own challenges. Kanban is a new development methodology quickly gaining popularity in the software development community. This thesis aims to answer the question: How does Kanban influence customer involvement? The main prob...

An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

Science.gov (United States)

Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

2016-02-01

The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

Multisensory softness perceived compliance from multiple sources of information

CERN Document Server

Luca, Massimiliano Di

2014-01-01

Offers a unique multidisciplinary overview of how humans interact with soft objects and how multiple sensory signals are used to perceive material properties, with an emphasis on object deformability. The authors describe a range of setups that have been employed to study and exploit sensory signals involved in interactions with compliant objects as well as techniques to simulate and modulate softness - including a psychophysical perspective of the field. Multisensory Softness focuses on the cognitive mechanisms underlying the use of multiple sources of information in softness perception. D

Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

International Nuclear Information System (INIS)

Merini, Luciano J.; Bobillo, Cecilia; Cuadrado, Virginia; Corach, Daniel; Giulietti, Ana M.

2009-01-01

Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg -1 of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P 450 or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P 450 . Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

Phytoremediation potential of the novel atrazine tolerant Lolium multiflorum and studies on the mechanisms involved

Energy Technology Data Exchange (ETDEWEB)

Merini, Luciano J. [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Bobillo, Cecilia [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Cuadrado, Virginia [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina); Corach, Daniel [Servicio de Huellas Digitales Geneticas, Facultad de Farmacia y Bioquimica, Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires, Junin 956, BS As (Argentina); Giulietti, Ana M., E-mail: agiule@ffyb.uba.a [Catedra de Microbiologia Industrial y Biotecnologia, Universidad de Buenos Aires (Argentina)

2009-11-15

Atrazine impact on human health and the environment have been extensively studied. Phytoremediation emerged as a low cost, environmental friendly biotechnological solution for atrazine pollution in soil and water. In vitro atrazine tolerance assays were performed and Lolium multiflorum was found as a novel tolerant species, able to germinate and grow in the presence of 1 mg kg{sup -1} of the herbicide. L. multiflorum presented 20% higher atrazine removal capacity than the natural attenuation, with high initial degradation rate in microcosms. The mechanisms involved in atrazine tolerance such as mutation in psbA gene, enzymatic detoxification via P{sub 450} or chemical hydrolysis through benzoxazinones were evaluated. It was demonstrated that atrazine tolerance is conferred by enhanced enzymatic detoxification via P{sub 450}. Due to its atrazine degradation capacity in soil and its agronomical properties, L. multiflorum is a candidate for designing phytoremediation strategies for atrazine contaminated agricultural soils, especially those involving run-off avoiding. - Finding of a novel atrazine-tolerant species, as a potential candidate for phytoremediating herbicide-contaminated agriculture soils and elucidation of the mechanisms involved in tolerance.

Effects of multiple disturbances in seagrass meadows : shading decreases resilience to grazing

NARCIS (Netherlands)

Eklof, Johan S.; McMahon, Kathryn; Lavery, Paul S.

2009-01-01

Ecosystem shifts are often associated with multiple disturbances, but limited knowledge on the mechanisms involved hampers management. This study investigated how short-term shading affected the resilience of the seagrass Halophila ovalis to grazing by black swans (Cygnus atratus) - a historically

New Insights on Neurobiological Mechanisms underlying Alcohol Addiction

Science.gov (United States)

Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

2012-01-01

Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence. PMID:23159531

Involvement of translation and transcription processes into neurophysiological mechanisms of long-term memory reconsolidation.

Science.gov (United States)

Kozyrev, S A; Nikitin, V P

2013-03-01

We studied the involvement of translation and transcription processes into behavioral and neuronal mechanisms of reconsolidation of the long-term memory of the conditioned taste aversion in edible snails. Injection of cycloheximide (an inhibitor of protein synthesis) to the snails in 48 h after training combined with subsequent reminder and presentation of the conditional stimulus resulted in the development of persistent amnesia and depression of the responses of the defensive behavior command neurons LPl1 and RPl1 to the conditional stimulus. Injection of mRNA synthesis inhibitors actinomycin D or DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidasole) in 48 h after conditioning with subsequent reminding procedure produced no effects on memory retention and on the responses of the command neurons to the conditional stimulus. The study suggests that the proteins translated from previously synthesized and stored mRNA were involved in the mechanisms of reconsolidation of the memory responsible for conditioned taste aversion.

On existence and multiplicity for Schrödinger–Poisson systems involving weighted sublinear nonlinearities

Directory of Open Access Journals (Sweden)

Sara Barile

2017-04-01

where $V, K: \\mathbb{R}^3 \\rightarrow \\mathbb{R}^+$ are suitable potentials and $f: \\mathbb{R}^3 \\times \\mathbb{R} \\rightarrow \\mathbb{R}$ satisfies sublinear growth assumptions involving a finite number of positive weights $W_i$, $i= 1,\\dots,r$ with $r \\geq 1$. By exploiting compact embeddings of the functional space on which we work in every weighted space $L_{W_i}^{w_i}(\\mathbb{R}^3$, $w_i \\in (1, 2$, we establish existence by means of a generalized Weierstrass theorem. Moreover, we prove multiplicity of solutions if $f$ is odd in $u$ and $g(x \\equiv 0$ thanks to a variant of the symmetric mountain pass theorem stated by R. Kajikiya for subquadratic functionals.

Energy transfer mechanism between manganese and neodymium

Energy Technology Data Exchange (ETDEWEB)

Kumar, R [Department of Physics, Government Raza Post-Graduate College, Rampur 244901, U.P., India

1977-01-01

The mechanism of energy transfer between Mn/sup 2 +/ ..-->.. Nd/sup 3 +/ in barium borate glass has been investigated. The change in emission intensities and lifetimes of Mn/sup 2 +/ (donor) due to the presence of Nd/sup 3 +/ (acceptor) are observed. It has been concluded that the mechanism of energy transfer involves a nonradiative resonance process. The electrostatic multiple interaction responsible for the transfer is dipole-dipole in nature.

Taking a(c)count of eye movements: Multiple mechanisms underlie fixations during enumeration.

Science.gov (United States)

Paul, Jacob M; Reeve, Robert A; Forte, Jason D

2017-03-01

We habitually move our eyes when we enumerate sets of objects. It remains unclear whether saccades are directed for numerosity processing as distinct from object-oriented visual processing (e.g., object saliency, scanning heuristics). Here we investigated the extent to which enumeration eye movements are contingent upon the location of objects in an array, and whether fixation patterns vary with enumeration demands. Twenty adults enumerated random dot arrays twice: first to report the set cardinality and second to judge the perceived number of subsets. We manipulated the spatial location of dots by presenting arrays at 0°, 90°, 180°, and 270° orientations. Participants required a similar time to enumerate the set or the perceived number of subsets in the same array. Fixation patterns were systematically shifted in the direction of array rotation, and distributed across similar locations when the same array was shown on multiple occasions. We modeled fixation patterns and dot saliency using a simple filtering model and show participants judged groups of dots in close proximity (2°-2.5° visual angle) as distinct subsets. Modeling results are consistent with the suggestion that enumeration involves visual grouping mechanisms based on object saliency, and specific enumeration demands affect spatial distribution of fixations. Our findings highlight the importance of set computation, rather than object processing per se, for models of numerosity processing.

Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

Science.gov (United States)

Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

2012-06-28

Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

OpenAIRE

Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

2015-01-01

We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on bra...

Hierarchy of mechanisms involved in generating Na/K-ATPase polarity in MDCK epithelial cells

NARCIS (Netherlands)

Mays, R.W.; Siemers, K.A.; Fritz, B.A.; Lowe, A.W.; van Meer, G.; Nelson, W.J.

1995-01-01

We have studied mechanisms involved in generating a polarized distribution of Na/K-ATPase in the basal-lateral membrane of two clones of MDCK II cells. Both clones exhibit polarized distributions of marker proteins of the apical and basal-lateral membranes, including Na/K-ATPase, at steady state.

A Novel Multiple-Bits Collision Attack Based on Double Detection with Error-Tolerant Mechanism

Directory of Open Access Journals (Sweden)

Ye Yuan

2018-01-01

Full Text Available Side-channel collision attacks are more powerful than traditional side-channel attack without knowing the leakage model or establishing the model. Most attack strategies proposed previously need quantities of power traces with high computational complexity and are sensitive to mistakes, which restricts the attack efficiency seriously. In this paper, we propose a multiple-bits side-channel collision attack based on double distance voting detection (DDVD and also an improved version, involving the error-tolerant mechanism, which can find all 120 relations among 16 key bytes when applied to AES (Advanced Encryption Standard algorithm. In addition, we compare our collision detection method called DDVD with the Euclidean distance and the correlation-enhanced collision method under different intensity of noise, which indicates that our detection technique performs better in the circumstances of noise. Furthermore, 4-bit model of our collision detection method is proven to be optimal in theory and in practice. Meanwhile the corresponding practical attack experiments are also performed on a hardware implementation of AES-128 on FPGA board successfully. Results show that our strategy needs less computation time but more traces than LDPC method and the online time for our strategy is about 90% less than CECA and 96% less than BCA with 90% success rate.

Fluorescence excitation involving multiple electron transition states of N{sub 2} and CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Wu, C.Y.R.; Chen, F.Z.; Hung, T.; Judge, D.L. [Univ. of Southern California, Los Angeles, CA (United States)

1997-04-01

The electronic states and electronic structures of N{sub 2} and CO{sub 2} in the 8-50 eV energy region have been studied extensively both experimentally and theoretically. In the energy region higher than 25 eV there exists many electronic states including multiple electron transition (MET) states which are responsible for producing most of the dissociative photoionization products. The electronic states at energies higher than 50 eV have been mainly determined by Auger spectroscopy, double charge transfer, photofragment spectroscopy and ion-ion coincidence spectroscopy. The absorption and ionization spectra of these molecules at energies higher than 50 eV mainly show a monotonic decrease in cross section values and exhibit structureless features. The decay channels of MET and Rydberg (or superexcited) states include autoionization, ionization, dissociative ionization, predissociation, and dissociation while those of single ion and multiple ion states may involve predissociation. and dissociation processes. The study of fluorescence specifically probes electronically excited species resulting from the above-mentioned decay channels and provides information for understanding the competition among these channels.

An Overview of Long Noncoding RNAs Involved in Bone Regeneration from Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Shuping Peng

2018-01-01

Full Text Available Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs are a family of transcripts longer than 200 nt without or with very low protein-coding potential. Recent studies have demonstrated that lncRNAs are widely involved in the regulation of lineage commitment and differentiation of stem cells through multiple mechanisms. In this review, we will summarize the roles and molecular mechanism of lncRNAs including H19, MALAT1, MODR, HOTAIR, DANCR, MEG3, HoxA-AS3, and MIAT in osteogenesis ossification; lncRNA ZBED3-AS1 and CTA-941F9.9, DANCR, and HIT in chondrogenic differentiation; and lncRNA DANCR in osteoclast differentiation. These findings will facilitate the development and application of novel molecular drugs which regulate the balance of bone formation and absorption.

Multiple and variable NHEJ-like genes are involved in resistance to DNA damage in Streptomyces ambofaciens

Directory of Open Access Journals (Sweden)

Grégory Hoff

2016-11-01

Full Text Available Non homologous end-joining (NHEJ is a double strand break (DSB repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing and ligation of the broken ends. In silico analyses performed in the 38 sequenced genomes of Streptomyces species revealed the existence of a large panel of NHEJ-like genes. Indeed, ku genes or ligD domain homologues are scattered throughout the genome in multiple copies and can be distinguished in two categories: the core NHEJ gene set constituted of conserved loci and the variable NHEJ gene set constituted of NHEJ-like genes present in only a part of the species. In Streptomyces ambofaciens ATCC 23877, not only the deletion of core genes but also that of variable genes led to an increased sensitivity to DNA damage induced by electron beam irradiation. Multiple mutants of ku, ligase or polymerase encoding genes showed an aggravated phenotype compared to single mutants. Biochemical assays revealed the ability of Ku-like proteins to protect and to stimulate ligation of DNA ends. RT-qPCR and GFP fusion experiments suggested that ku-like genes show a growth phase dependent expression profile consistent with their involvement in DNA repair during spores formation and/or germination.

Active joint mechanism driven by multiple actuators made of flexible bags: a proposal of dual structural actuator.

Science.gov (United States)

Kimura, Hitoshi; Matsuzaki, Takuya; Kataoka, Mokutaro; Inou, Norio

2013-01-01

An actuator is required to change its speed and force depending on the situation. Using multiple actuators for one driving axis is one of the possible solutions; however, there is an associated problem of output power matching. This study proposes a new active joint mechanism using multiple actuators. Because the actuator is made of a flexible bag, it does not interfere with other actuators when it is depressurized. The proposed joint achieved coordinated motion of multiple actuators. This report also discusses a new actuator which has dual cylindrical structure. The cylinders are composed of flexible bags with different diameters. The joint torque is estimated based on the following factors: empirical formula for the flexible actuator torque, geometric relationship between the joint and the actuator, and the principle of virtual work. The prototype joint mechanism achieves coordinated motion of multiple actuators for one axis. With this motion, small inner actuator contributes high speed motion, whereas large outer actuator generates high torque. The performance of the prototype joint is examined by speed and torque measurements. The joint showed about 30% efficiency at 2.0 Nm load torque under 0.15 MPa air input.

Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

Science.gov (United States)

Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

2015-01-01

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

F18 FDG positron emission tomography revelation of primary testicular lymphoma with concurrent multiple extra nodal involvement

International Nuclear Information System (INIS)

Vamsy, Mohana; Dattatreya, P.S.; Parakh, Megha; Dayal, Monal; Prabhakar Rao, V.V.S.

2013-01-01

Primary testicular lymphoma (PTL) a relatively rare disease of non-Hodgkin's lymphomas occurring with a lesser incidence of 1-2% has a propensity to occur at later ages above 50 years. PTL spreads to extra nodal sites due to deficiency of extra cellular adhesion molecules. We present detection of multiple sites of extra nodal involvement of PTL by F-18 positron emission tomography/computed tomography study aiding early detection of the dissemination thus aiding in staging and management. (author)

Pharmacologic pre- and postconditioning for stroke: Basic mechanisms and translational opportunity

Directory of Open Access Journals (Sweden)

Elga Esposito

2015-01-01

Full Text Available Beyond reperfusion therapies, there are still no widely effective therapies for ischemic stroke. Although much progress has been made to define the molecular pathways involved, targeted neuroprotective strategies have often failed in clinical trials. An emerging hypothesis suggests that focusing on single targets and mechanisms may not work since ischemic stroke triggers multiple pathways in multiple cell types. In this review, we briefly survey and assess the opportunities that may be afforded by pre- and postconditioning therapies, with particular attention to pharmacologic pre- and postconditioning. Pharmacologic conditioning may be defined as the use of chemical agents either before or shortly after stroke onset to trigger mechanisms of endogenous tolerance that are thought to involve evolutionarily conserved signals that offer broad protection against ischemia. Importantly, many of the pharmacologic agents may also have been previously used in humans, thus providing hope for translating basic mechanisms into clinical applications.

Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

Directory of Open Access Journals (Sweden)

M.P. da Silva

2014-02-01

Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

Directory of Open Access Journals (Sweden)

Mohammad F Saeed

2010-09-01

Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

Numerical and Experimental Study of Mechanisms Involved in Boiling Histotripsy.

Science.gov (United States)

Pahk, Ki Joo; Gélat, Pierre; Sinden, David; Dhar, Dipok Kumar; Saffari, Nader

2017-12-01

The aim of boiling histotripsy is to mechanically fractionate tissue as an alternative to thermal ablation for therapeutic applications. In general, the shape of a lesion produced by boiling histotripsy is tadpole like, consisting of a head and a tail. Although many studies have demonstrated the efficacy of boiling histotripsy for fractionating solid tumors, the exact mechanisms underpinning this phenomenon are not yet well understood, particularly the interaction of a boiling vapor bubble with incoming incident shockwaves. To investigate the mechanisms involved in boiling histotripsy, a high-speed camera with a passive cavitation detection system was used to observe the dynamics of bubbles produced in optically transparent tissue-mimicking gel phantoms exposed to the field of a 2.0-MHz high-intensity focused ultrasound (HIFU) transducer. We observed that boiling bubbles were generated in a localized heated region and cavitation clouds were subsequently induced ahead of the expanding bubble. This process was repeated with HIFU pulses and eventually resulted in a tadpole-shaped lesion. A simplified numerical model describing the scattering of the incident ultrasound wave by a vapor bubble was developed to help interpret the experimental observations. Together with the numerical results, these observations suggest that the overall size of a lesion induced by boiling histotripsy is dependent on the sizes of (i) the heated region at the HIFU focus and (ii) the backscattered acoustic field by the original vapor bubble. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms : Involvement of JNK and ERK MAP kinases

NARCIS (Netherlands)

Conde de la Rosa, L; Schoemaker, MH; Vrenken, TE; Buist-Homan, M; Havinga, R; Jansen, PLM; Moshage, H

Background/Aims: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases

NARCIS (Netherlands)

Conde de la Rosa, Laura; Schoemaker, Marieke H.; Vrenken, Titia E.; Buist-Homan, Manon; Havinga, Rick; Jansen, Peter L. M.; Moshage, Han

2006-01-01

BACKGROUND/AIMS: In liver diseases, reactive oxygen species (ROS) are involved in cell death and liver injury, but the mechanisms are not completely elucidated. To elucidate the mechanisms of hepatocyte cell death induced by the ROS superoxide anions and hydrogen peroxide, primary cultures of

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

Directory of Open Access Journals (Sweden)

Marta Herranz

2018-01-01

Full Text Available Background:Mycobacterium tuberculosis (MTB has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs between isolates.Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts.Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission.Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed.Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.

Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS) : study protocol for a randomized controlled trial

NARCIS (Netherlands)

Cambron, Melissa; Mostert, Jop; Haentjens, Patrick; D'Hooghe, Marie; Nagels, Guy; Willekens, Barbara; Heersema, Dorothea; Debruyne, Jan; Van Hecke, Wim; Algoed, Luc; De Klippel, Nina; Fosselle, Erwin; Laureys, Guy; Merckx, Henri; Van Wijmeersch, Bart; Vanopdenbosch, Ludo; Verhagen, Wim; Hupperts, Raymond; Hengstman, Gerald; Michiels, Veronique; Van Merhaegen-Wieleman, Annick; De Keyser, Jacques

2014-01-01

Background: Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced

involvement of multiple cell lineages in atherogenesis

African Journals Online (AJOL)

2017-07-12

Jul 12, 2017 ... Elucidation of all ... molecular mechanisms which underly this .... intima. Monocyte chemoattractant protein-1 ... cell interaction, release of microparticles, pro – ..... Monocytes and macrophages dynamics during atherogenesis.

Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms.

Science.gov (United States)

Vidal-Dupiol, Jeremie; Adjeroud, Mehdi; Roger, Emmanuel; Foure, Laurent; Duval, David; Mone, Yves; Ferrier-Pages, Christine; Tambutte, Eric; Tambutte, Sylvie; Zoccola, Didier; Allemand, Denis; Mitta, Guillaume

2009-08-04

Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28 degrees C to 32 degrees C over 15 days. A second control set kept at constant temperature (28 degrees C). The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching) and the non stressed states (control) were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function) were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin) contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich). Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress. Under thermal stress

In Vitro Effect of Malachite Green on Candida albicans Involves Multiple Pathways and Transcriptional Regulators UPC2 and STP2

Science.gov (United States)

Dhamgaye, Sanjiveeni; Devaux, Frederic; Manoharlal, Raman; Vandeputte, Patrick; Shah, Abdul Haseeb; Singh, Ashutosh; Blugeon, Corinne; Sanglard, Dominique

2012-01-01

In this study, we show that a chemical dye, malachite green (MG), which is commonly used in the fish industry as an antifungal, antiparasitic, and antibacterial agent, could effectively kill Candida albicans and non-C. albicans species. We have demonstrated that Candida cells are susceptible to MG at a very low concentration (MIC that reduces growth by 50% [MIC50], 100 ng ml−1) and that the effect of MG is independent of known antifungal targets, such as ergosterol metabolism and major drug efflux pump proteins. Transcriptional profiling in response to MG treatment of C. albicans cells revealed that of a total of 207 responsive genes, 167 genes involved in oxidative stress, virulence, carbohydrate metabolism, heat shock, amino acid metabolism, etc., were upregulated, while 37 genes involved in iron acquisition, filamentous growth, mitochondrial respiration, etc., were downregulated. We confirmed experimentally that Candida cells exposed to MG resort to a fermentative mode of metabolism, perhaps due to defective respiration. In addition, we showed that MG triggers depletion of intracellular iron pools and enhances reactive oxygen species (ROS) levels. These effects could be reversed by the addition of iron or antioxidants, respectively. We provided evidence that the antifungal effect of MG is exerted through the transcription regulators UPC2 (regulating ergosterol biosynthesis and azole resistance) and STP2 (regulating amino acid permease genes). Taken together, our transcriptome, genetic, and biochemical results allowed us to decipher the multiple mechanisms by which MG exerts its anti-Candida effects, leading to a metabolic shift toward fermentation, increased generation of ROS, labile iron deprivation, and cell necrosis. PMID:22006003

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

Directory of Open Access Journals (Sweden)

Andrea Mike

Full Text Available Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus. Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed, processing of emotions (right entorhinal cortex and socially relevant information (left temporal pole. Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

Science.gov (United States)

Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

2013-01-01

Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats

Directory of Open Access Journals (Sweden)

Yano Takahisa

2011-01-01

Full Text Available Abstract Background Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of acute and chronic peripheral neuropathies. The chronic neuropathy is a dose-limiting toxicity. We previously reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats. In the present study, we investigated the involvement of NR2B-containing N-methyl-D-aspartate (NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Results Repeated administration of oxaliplatin (4 mg/kg, i.p., twice a week caused mechanical allodynia in the fourth week, which was reversed by intrathecal injection of MK-801 (10 nmol and memantine (1 μmol, NMDA receptor antagonists. Similarly, selective NR2B antagonists Ro25-6981 (300 nmol, i.t. and ifenprodil (50 mg/kg, p.o. significantly attenuated the oxaliplatin-induced pain behavior. In addition, the expression of NR2B protein and mRNA in the rat spinal cord was increased by oxaliplatin on Day 25 (late phase but not on Day 5 (early phase. Moreover, we examined the involvement of nitric oxide synthase (NOS as a downstream target of NMDA receptor. L-NAME, a non-selective NOS inhibitor, and 7-nitroindazole, a neuronal NOS (nNOS inhibitor, significantly suppressed the oxaliplatin-induced pain behavior. The intensity of NADPH diaphorase staining, a histochemical marker for NOS, in the superficial layer of spinal dorsal horn was obviously increased by oxaliplatin, and this increased intensity was reversed by intrathecal injection of Ro25-6981. Conclusion These results indicated that spinal NR2B-containing NMDA receptors are involved in the oxaliplatin-induced mechanical allodynia.

Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches.

Science.gov (United States)

Hajishengallis, George; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Lambris, John D

2015-01-01

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

Different Mechanisms of Inflammation Induced in Virus and Autoimmune-Mediated Models of Multiple Sclerosis in C57BL6 Mice

Directory of Open Access Journals (Sweden)

Abhinoy Kishore

2013-01-01

Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease of the human central nervous system (CNS. Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59 induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG induces experimental autoimmune encephalomyelitis (EAE, a mainly CD4+ T-cell-mediated disease, although CD8+ T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as direct viral toxicity may induce MS. Our study directly compares CNS pathology in autoimmune and viral-induced MS models. Mice with viral-induced and EAE demyelinating diseases demonstrated similar patterns and distributions of demyelination that accumulated over the course of the disease. However, significant differences in acute inflammation were noted. Inflammation was restricted mainly to white matter at all times in EAE, whereas inflammation initially largely involved gray matter in acute MHV-induced disease and then is subsequently localized only in white matter in the chronic disease phase. The presence of dual mechanisms of demyelination may be responsible for the failure of immunosuppression to promote long-term remission in many MS patients.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

DEFF Research Database (Denmark)

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti

2011-01-01

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown...... the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture...... underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working...

Structural networks involved in attention and executive functions in multiple sclerosis

Directory of Open Access Journals (Sweden)

Sara Llufriu

2017-01-01

Full Text Available Attention and executive deficits are disabling symptoms in multiple sclerosis (MS that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA of white matter (WM connections or edges between 72 MS subjects and 38 healthy volunteers (HV and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected. Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected. Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected. Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices were associated with worse functioning (r between −0.40 and −0.47, p < 0.05 corrected. In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of

Adaption of Ulva pertusa to multiple-contamination of heavy metals and nutrients: Biological mechanism of outbreak of Ulva sp. green tide.

Science.gov (United States)

Ge, Changzi; Yu, Xiru; Kan, Manman; Qu, Chunfeng

2017-12-15

The multiple-contamination of heavy metals and nutrients worsens increasingly and Ulva sp. green tide occurs almost simultaneously. To reveal the biological mechanism for outbreak of the green tide, Ulva pertusa was exposed to seven-day-multiple-contamination. The relation between pH variation (V pH ), Chl a content, ratio of (Chl a content)/(Chl b content) (R chla/chlb ), SOD activity of U. pertusa (A SOD ) and contamination concentration is [Formula: see text] (pcontamination concentrations of seawaters where Ulva sp. green tide occurred and the contamination concentrations set in the present work, U. pertusa can adapt to multiple-contaminations in these waters. Thus, the adaption to multiple-contamination may be one biological mechanism for the outbreak of Ulva sp. green tide. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms

DEFF Research Database (Denmark)

Nestoras, Konstantinos; Mohammed, Asma Hadi; Schreurs, Ann-Sofie

2010-01-01

The correct levels of deoxyribonucleotide triphosphates and their relative abundance are important to maintain genomic integrity. Ribonucleotide reductase (RNR) regulation is complex and multifaceted. RNR is regulated allosterically by two nucleotide-binding sites, by transcriptional control, and...

Evidence for the involvement of MC4 receptors in the central mechanisms of opioid antinociception

NARCIS (Netherlands)

Starowicz, Katarzyna

2005-01-01

The data described in this thesis extend general knowledge of the involvement of the MC4 receptor in mechanisms of analgesia. The following aspects outlined below constitute novel information. Firstly, the MC4R localization in the DRG is demonstrated. The MC4 receptor was assumed to exist

Multiple trauma in children: critical care overview.

Science.gov (United States)

Wetzel, Randall C; Burns, R Cartland

2002-11-01

Multiple trauma is more than the sum of the injuries. Management not only of the physiologic injury but also of the pathophysiologic responses, along with integration of the child's emotional and developmental needs and the child's family, forms the basis of trauma care. Multiple trauma in children also elicits profound psychological responses from the healthcare providers involved with these children. This overview will address the pathophysiology of multiple trauma in children and the general principles of trauma management by an integrated trauma team. Trauma is a systemic disease. Multiple trauma stimulates the release of multiple inflammatory mediators. A lethal triad of hypothermia, acidosis, and coagulopathy is the direct result of trauma and secondary injury from the systemic response to trauma. Controlling and responding to the secondary pathophysiologic sequelae of trauma is the cornerstone of trauma management in the multiply injured, critically ill child. Damage control surgery is a new, rational approach to the child with multiple trauma. The selection of children for damage control surgery depends on the severity of injury. Major abdominal vascular injuries and multiple visceral injuries are best considered for this approach. The effective management of childhood multiple trauma requires a combined team approach, consideration of the child and family, an organized trauma system, and an effective quality assurance and improvement mechanism.

Study of multiple production mechanisms of neutral and charged particles in proton-proton interactions at 69GeV/c

International Nuclear Information System (INIS)

Boratav, Murat.

1976-01-01

From a sample of 30000 pictures taken in the hydrogen bubble chamber Mirabelle, with a proton beam of 69GeV/c, at Serpukhov, the multiple particle production mechanisms are studied in proton-proton collisions. The neutral pions produced are specially studied, which means that the photons coming from the disintegration of π 0 's have to be detected and measured. From these pion spectra, their multiplicity distributions and the first order moments of these distributions (particularly the Mueller correlation coefficients) data and results are compared with the predictions of theoretical models such as: 'thermodynamic' models (Feynman gas, critical fluid model, etc.) and cluster models (with a fixed size or a size depending on incoming energy). The multiple production mechanisms seem to appear through small-sized, energy-dependent clusters (about two pions per cluster at this energy) [fr

The Effects of Multiple Sets of Squats and Jump Squats on Mechanical Variables.

Science.gov (United States)

Rossetti, Michael L; Munford, Shawn N; Snyder, Brandon W; Davis, Shala E; Moir, Gavin L

2017-07-28

The mechanical responses to two non-ballistic squat and two ballistic jump squat protocols performed over multiple sets were investigated. One protocol from each of the two non-ballistic and ballistic conditions incorporated a pause between the eccentric and concentric phases of the movements in order to determine the influence of the coupling time on the mechanical variables and post-activation potentiation (PAP). Eleven men (age: 21.9 ± 1.8 years; height: 1.79 ± 0.05 m; mass: 87.0 ± 7.4 kg) attended four sessions where they performed multiple sets of squats and jump squats with a load equivalent to 30% 1-repeititon maximum under one of the following conditions: 1) 3 × 4 repetitions of non-ballistic squats (30N-B); 2) 3 × 4 repetitions of non-ballistic squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PN-B); 3) 3 × 4 repetitions of ballistic jump squats (30B); 4) 3 × 4 repetitions of ballistic jump squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PB). Force plates were used to calculate variables including average vertical velocity, average vertical force (GRF), and average power output (PO). Vertical velocities during the ballistic conditions were significantly greater than those attained during the non-ballistic conditions (mean differences: 0.21 - 0.25 m/s, p0.05). Ballistic jump squats may be an effective exercise for developing PO given the high velocities and forces generated in these exercises. Furthermore, the completion of multiple sets of jump squats may induce PAP to enhance PO. The coupling times between the eccentric and concentric phases of the jump squats should be short in order to maximize the GRF and PO across the sets.

Multiple proteins of White spot syndrome virus involved in ...

Indian Academy of Sciences (India)

The recognition and attachment of virus to its host cell surface is a critical step for viral infection. Recent research revealed that -integrin was involved in White spot syndrome virus (WSSV) infection. In this study, the interaction of -integrin with structure proteins of WSSV and motifs involved in WSSV infection was ...

Sudden multiple fractures in a patient with sarcoidosis in multiple organs.

Science.gov (United States)

Sada, Mitsuru; Saraya, Takeshi; Ishii, Haruyuki; Goto, Hajime

2014-04-07

A 30-year-old man who incidentally fractured his right olecranon and other multiple phalanges was admitted to our hospital. He had a 2-year history of uveitis and bilateral hilar lymphadenopathy (BHL), and pulmonary sarcoidosis was diagnosed from transbronchial lung biopsy. Right elbow arthrodesis was performed, and biopsied specimens showed non-caseating epithelioid cell granuloma, suggesting osseous sarcoidosis. He was discharged uneventfully without further treatment, but BHL had progressed with the appearance of lung parenchymal lesions 3 months later. At that time, involvement of other organs was also noted on Gallium-67 scintigraphy, showing accumulations in BHL, axillary and inguinal lymph nodes, enlarged liver and spleen and subcutaneous areas. After initiation of steroid therapy, multiple organ involvement improved, and no further bone involvement has been recognised to date. Osseous sarcoidosis complicated by bone fracture is an extremely rare presentation, but should be considered in patients with sarcoidosis, especially when multiple organs are involved.

Identification of Multiple-Mode Linear Models Based on Particle Swarm Optimizer with Cyclic Network Mechanism

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Tae-Hyoung Kim

2017-01-01

Full Text Available This paper studies the metaheuristic optimizer-based direct identification of a multiple-mode system consisting of a finite set of linear regression representations of subsystems. To this end, the concept of a multiple-mode linear regression model is first introduced, and its identification issues are established. A method for reducing the identification problem for multiple-mode models to an optimization problem is also described in detail. Then, to overcome the difficulties that arise because the formulated optimization problem is inherently ill-conditioned and nonconvex, the cyclic-network-topology-based constrained particle swarm optimizer (CNT-CPSO is introduced, and a concrete procedure for the CNT-CPSO-based identification methodology is developed. This scheme requires no prior knowledge of the mode transitions between subsystems and, unlike some conventional methods, can handle a large amount of data without difficulty during the identification process. This is one of the distinguishing features of the proposed method. The paper also considers an extension of the CNT-CPSO-based identification scheme that makes it possible to simultaneously obtain both the optimal parameters of the multiple submodels and a certain decision parameter involved in the mode transition criteria. Finally, an experimental setup using a DC motor system is established to demonstrate the practical usability of the proposed metaheuristic optimizer-based identification scheme for developing a multiple-mode linear regression model.

Pathogenic Mechanisms Involved in the Hematological Alterations of Arenavirus-induced Hemorrhagic Fevers

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Roberto G. Pozner

2013-01-01

Full Text Available Viral hemorrhagic fevers (VHFs caused by arenaviruses are acute diseases characterized by fever, headache, general malaise, impaired cellular immunity, eventual neurologic involvement, and hemostatic alterations that may ultimately lead to shock and death. The causes of the bleeding are still poorly understood. However, it is generally accepted that these causes are associated to some degree with impaired hemostasis, endothelial cell dysfunction and low platelet counts or function. In this article, we present the current knowledge about the hematological alterations present in VHF induced by arenaviruses, including new aspects on the underlying pathogenic mechanisms.

Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

Directory of Open Access Journals (Sweden)

Juan Ignacio Rojas

2016-03-01

Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

Directory of Open Access Journals (Sweden)

Tambutte Sylvie

2009-08-01

Full Text Available Abstract Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C. The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching and the non stressed states (control were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich. Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress

Multiplicative formulation of quantum mechanics

International Nuclear Information System (INIS)

Voros, A.; Leboeuf, P.

1991-01-01

A general semi-classical description for the eigenfunctions of the multidimensional Schroedinger operator cannot be based on the WKB method which is incompatible with classically ergodic behavior. An alternative, more general multiplicative parametrization of quantum wave functions is suggested, whereby the semi-classical behavior of eigenfunctions can be traced in the presence of classical ergodicity, in the form of diffusive patterns of phase-space zeros in the quantum wave functions. (author) 24 refs.; 4 figs

An unusual presentation of brucellosis, involving multiple organ systems, with low agglutinating titers: a case report

Directory of Open Access Journals (Sweden)

Khorvash Farzin

2007-07-01

Full Text Available Abstract Background Brucellosis is a multi-system disease that may present with a broad spectrum of clinical manifestations. While hepatic involvement in brucellosis is not rare, it may rarely involve the kidney or display with cardiac manifestations. Central nervous system involvement in brucellosis sometimes can cause demyelinating syndromes. Here we present a case of brucella hepatitis, myocarditis, acute disseminated encephalomyelitis, and renal failure. Case presentation A 26-year-old man presented with fever, ataxia, and dysarthria. He was a shepherd and gave a history of low grade fever, chilly sensation, cold sweating, loss of appetite, arthralgia and 10 Kg weight loss during the previous 3 months. He had a body temperature of 39°C at the time of admission. On laboratory tests he had elevated level of liver enzymes, blood urea nitrogen, Creatinine, Creatine phosphokinase (MB, and moderate proteinuria. He also had abnormal echocardiography and brain MRI. Enzyme-linked immunosorbent assay for IgG and IgM was negative. Standard tube agglutination test (STAT and 2-mercaptoethanol (2-ME titers were 1:80 and 1:40 respectively. Finally he was diagnosed with brucellosis by positive blood culture and the polymerase chain reaction for Brucella mellitensis. Conclusion In endemic areas clinicians should consider brucellosis in any unusual presentation involving multiple organ systems, even if serology is inconclusive. In endemic areas low STAT and 2-ME titers should be considered as an indication of brucellosis and in these cases additional testing is recommended to rule out brucellosis.

Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis

Directory of Open Access Journals (Sweden)

Martin M. Herrmann

2016-10-01

Full Text Available After encounter with a central nervous system (CNS-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1 rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

Multiple mechanisms of PCB neurotoxicity

Energy Technology Data Exchange (ETDEWEB)

Carpenter, D.O.; Stoner, C.T.; Lawrence, D.A. [Univ. of New York, Albany, NY (United States)] [and others

1996-12-31

Polychlorinated biphenyls (PCBs) have been implicated in cancer, but many of the symptoms in humans exposed to PCBs are related to the nervous system and behavior. We demonstrated three different direct mechanisms whereby PCBs are neurotoxic in rats. By using flow cytometry, we demonstrated that the orthosubstituted PCB congener 2,4,4{prime}, but neither TCDD nor the coplanar PCB congener 3,4,5,3{prime},4{prime}, causes rapid death of cerebellar granule cells. The ortho-substituted congener 2,4,4{prime} reduced long-term potentiation, an indicator of cognitive potential, in hippocampal brain slices, but a similar effect was observed for the coplanar congener 3,4,3{prime},4{prime}, indicating that this effect may be caused by both ortho- and coplanar congeners by mechanisms presumably not mediated via the Ah receptor. It was previously shown that some ortho-substituted PCB congeners cause a reduction in levels of the neurotransmitter dopamine, and we present in vitro and in vivo evidence that this is due to reduction of synthesis of dopamine via inhibition of the enzyme tyrosine hydroxylase. Thus, PCBs have a variety of mechanisms of primary neurotoxicity, and neurotoxicity is a characteristic of ortho-substituted, non-dioxin-like congeners as well as some coplanar congeners. The relative contribution of each of these mechanisms to the loss of cognitive function in humans exposed to PCBs remains to be determined. 42 refs., 3 figs., 1 tab.

Cannabidiol inhibits angiogenesis by multiple mechanisms.

Science.gov (United States)

Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

2012-11-01

Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Mechanisms and factors involved in hip injuries during frontal crashes.

Science.gov (United States)

Yoganandan, N; Pintar, F A; Gennarelli, T A; Maltese, M R; Eppinger, R H

2001-11-01

This study was conducted to collect data and gain insights relative to the mechanisms and factors involved in hip injuries during frontal crashes and to study the tolerance of hip injuries from this type of loading. Unembalmed human cadavers were seated on a standard automotive seat (reinforced) and subjected to knee impact test to each lower extremity. Varying combinations of flexion and adduction/abduction were used for initial alignment conditions and pre-positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate system. A load cell on the front of the pendulum recorded the impact force. Peak impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123 to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were not apparent in three tests. Eight tests resulted in trauma. Fractures involving the pelvis including the acetabulum and proximal femur occurred in five out of the eight tests, and distal femoral bone fracture occurred in one test. These results underscore the importance of leg pre-positioning and the orientation of the impacting axis to produce specific types of trauma to the pelvic region of the lower extremity.

Multiple self-healing squamous epithelioma er en arvelig tilstand med selvhelende hudkræft

DEFF Research Database (Denmark)

Broesby-Olsen, Sigurd; Frandsen, Stine Krog; Thomassen, Mads

2012-01-01

Multiple self-healing squamous epithelioma - Ferguson-Smith disease (MSSE) is an autosomal dominant inherited disease with multiple, recurrent, histologically malignant tumours that undergo spontaneous regression. The gene for MSSE has recently been identified as the transforming growth factor-be......-beta receptor 1 (TGFBR1). Although rare, MSSE constitutes an important model of tumour-biology research. The discovery of the genetic background for MSSE paves the way for further elucidating the mechanisms involved in this peculiar self-healing cancer syndrome....

Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

Energy Technology Data Exchange (ETDEWEB)

Rizzuto, F.; Spikes, J.D.

1975-01-01

A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms*

Science.gov (United States)

Grimm, Marcus O. W.; Kuchenbecker, Johanna; Grösgen, Sven; Burg, Verena K.; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Friess, Petra; de Wilde, Martijn C.; Broersen, Laus M.; Penke, Botond; Péter, Mária; Vígh, László; Grimm, Heike S.; Hartmann, Tobias

2011-01-01

Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects. PMID:21324907

Learning with Multiple Representations: An Example of a Revision Lesson in Mathematics

Science.gov (United States)

Wong, Darren; Poo, Sng Peng; Hock, Ng Eng; Kang, Wee Loo

2011-01-01

We describe an example of learning with multiple representations in an A-level revision lesson on mechanics. The context of the problem involved the motion of a ball thrown vertically upwards in air and studying how the associated physical quantities changed during its flight. Different groups of students were assigned to look at the ball's motion…

The mechanisms involved at the cell level; Les mecanismes mis en jeu au niveau cellulaire

Energy Technology Data Exchange (ETDEWEB)

Leblanc, G.; Pourcher, Th.; Perron, B. [Nice Univ., Dir. des Sciences du Vivant, Dept. de Biologie Joliot-Curie, 06 (France); Guillain, F. [CEA Grenoble, Dir. des Sciences du Vivant, 38 (France); Quemeneur, E. [CEA Marcoule, Dir. des Sciences du Vivant, 30 (France); Fritsch, P. [CEA Bruyeres le Chatel, Dir. des Sciences du Vivant, 91 (France)

2003-07-01

The mechanisms responsible at the cell level for inducing toxic reactions after contamination are as yet only imperfectly known. Work still needs to be done for both contaminants that have a biological role, such as iodine, and those that do not, such as cadmium, uranium and plutonium. In particular, these mechanisms bring into play, in biological membranes, carriers which are the physiological partners responsible for material exchange with the environment or inside the body. As they lack absolute selectivity, these carriers, which are involved in the assimilation and accumulation of vital mineral elements, also have the ability to transport toxic elements and isotopes. (authors)

Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

Directory of Open Access Journals (Sweden)

Daniela Marasco

2015-04-01

Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

Vitamin D and remyelination in multiple sclerosis.

Science.gov (United States)

Matías-Guíu, J; Oreja-Guevara, C; Matias-Guiu, J A; Gomez-Pinedo, U

2018-04-01

Several studies have found an association between multiple sclerosis and vitamin D (VD) deficiency, which suggests that VD may play a role in the immune response. However, few studies have addressed its role in remyelination. The VD receptor and the enzymes transforming VD into metabolites which activate the VD receptor are expressed in central nervous system (CNS) cells, which suggests a potential effect of VD on the CNS. Both in vitro and animal model studies have shown that VD may play a role in myelination by acting on factors that influence the microenvironment which promotes both proliferation and differentiation of neural stem cells into oligodendrocyte progenitor cells and oligodendrocytes. It remains unknown whether the mechanisms of internalisation of VD in the CNS are synergistic with or antagonistic to the mechanisms that facilitate the entry of VD metabolites into immune cells. VD seems to play a role in the CNS and our hypothesis is that VD is involved in remyelination. Understanding the basic mechanisms of VD in myelination is necessary to manage multiple sclerosis patients with VD deficiency. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

Directory of Open Access Journals (Sweden)

Aïsha Sahaï

2017-10-01

Full Text Available Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.

Multiple mechanisms quench passive spiral galaxies

Science.gov (United States)

Fraser-McKelvie, Amelia; Brown, Michael J. I.; Pimbblet, Kevin; Dolley, Tim; Bonne, Nicolas J.

2018-02-01

We examine the properties of a sample of 35 nearby passive spiral galaxies in order to determine their dominant quenching mechanism(s). All five low-mass (M⋆ environments. We postulate that cluster-scale gas stripping and heating mechanisms operating only in rich clusters are required to quench low-mass passive spirals, and ram-pressure stripping and strangulation are obvious candidates. For higher mass passive spirals, while trends are present, the story is less clear. The passive spiral bar fraction is high: 74 ± 15 per cent, compared with 36 ± 5 per cent for a mass, redshift and T-type matched comparison sample of star-forming spiral galaxies. The high mass passive spirals occur mostly, but not exclusively, in groups, and can be central or satellite galaxies. The passive spiral group fraction of 74 ± 15 per cent is similar to that of the comparison sample of star-forming galaxies at 61 ± 7 per cent. We find evidence for both quenching via internal structure and environment in our passive spiral sample, though some galaxies have evidence of neither. From this, we conclude no one mechanism is responsible for quenching star formation in passive spiral galaxies - rather, a mixture of mechanisms is required to produce the passive spiral distribution we see today.

Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms.

Science.gov (United States)

Chastanet, Arnaud; Losick, Richard

2011-11-01

The response regulator Spo0A governs multiple developmental processes in Bacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of spo0A is governed by a promoter switching mechanism, involving a vegetative, σ(A)-recognized promoter, P(v), and a sporulation σ(H)-recognized promoter, P(s), that is under phosphorylated Spo0A (Spo0A∼P) control. The spo0A regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their proximity to the coding sequence. Here we report that O(1) is responsible for repressing P(v) during the transition to stationary phase, that O(2) is responsible for repressing P(s) during growth, that O(3) is responsible for activating P(s) at the start of sporulation, and that O(4) is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P(v) is impeded due to RNA secondary structure whereas mRNAs originating from P(s) are fully competent for protein synthesis. We propose that the opposing actions of O(2) and O(3) and the enhanced translatability of mRNAs originating from P(s) create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.

Effects of Time-Compressed Speech Training on Multiple Functional and Structural Neural Mechanisms Involving the Left Superior Temporal Gyrus.

Science.gov (United States)

Maruyama, Tsukasa; Takeuchi, Hikaru; Taki, Yasuyuki; Motoki, Kosuke; Jeong, Hyeonjeong; Kotozaki, Yuka; Nakagawa, Seishu; Nouchi, Rui; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Sakaki, Kohei; Sasaki, Yukako; Magistro, Daniele; Kawashima, Ryuta

2018-01-01

Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension.

Involvement of the nitric oxide in melatonin-mediated protection against injury.

Science.gov (United States)

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Multiple-state Feshbach resonances mediated by high-order couplings

International Nuclear Information System (INIS)

Hemming, Christopher J.; Krems, Roman V.

2008-01-01

We present a study of multistate Feshbach resonances mediated by high-order couplings. Our analysis focuses on a system with one open scattering state and multiple bound states. The scattering state is coupled to one off-resonant bound state and multiple Feshbach resonances are induced by a sequence of indirect couplings between the closed channels. We derive a general recursive expression that can be used to fit the experimental data on multistate Feshbach resonances involving one continuum state and several bound states and present numerical solutions for several model systems. Our results elucidate general features of multistate Feshbach resonances induced by high-order couplings and suggest mechanisms for controlling collisions of ultracold atoms and molecules with external fields

Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

OpenAIRE

Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

2014-01-01

Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

Swarming mechanisms in the yellow fever mosquito: aggregation pheromones involved in the mating behavior of Aedes aegypti

Science.gov (United States)

Mosquitoes of various species mate in swarms comprised of tens to thousands flying males. Yet little information is known about mosquito swarming mechanism. Discovering chemical cues involved in mosquito biology leads to better adaptation of disease control interventions. In this study, we aimed ...

[Case of suspected multiple sclerosis with transcallosal lesions involving the upper surface of the corpus callosum].

Science.gov (United States)

Shirafuji, Toshihiko; Oya, Yasushi; Nakamura, Harumasa; Ogata, Katsuhisa; Ogawa, Masafumi; Kawai, Mitsuru

2008-05-01

A 26-year-old woman noticed gradually progressive, right lower leg weakness over a 1.5-month period. Neurological examination revealed right hemiparesis with slightly increased deep tendon reflexes, Babinski's sign on the right side, loss of position sense in the right leg, and slight loss of superficial sensation in the right toes. MR FLAIR images showed a high intensity area measuring 5 x 2 x 3 cm in the left frontal lobe, extending to the outer surface of the body of the corpus callosum and the adjacent right cingulate gyrus. Gadolinium enhancement was seen along the cortex and the outer surface of the body of the corpus callosum. CSF findings showed no pleocytosis, a protein content of 32 mg/dl, a sugar level of 85 mg/dl, and an IgG index of 0.46. The biopsy specimen obtained from the superior frontal gyrus showed perivascular cuffing of T-lymphocytes and some B-lymphocytes, as well as multiple small foci of demyelination. Starting on the second day of admission, the patient was treated with methylprednisolone pulse therapy (1,000 mg/day for 3 days); she was then switched to oral prednisolone (20 mg/day). Thereafter, the patient had two clinical relapses: one was due to a lesion in the dorsal part of the medulla oblongata associated with a disturbance of deep sensation in both hands, and the other was due to a lesion involving the right internal capsule, the globus pallidus, and the caudate nucleus associated with left facial nerve palsy. Visual evoked potentials suggested a demyelinating lesion in the right optic nerve. We suspected a diagnosis of multiple sclerosis based on the presence of more than two clinical episodes of neurological deficits with identifiable lesions on MRI. Multiple sclerosis should be considered in the differential diagnosis of lesions located in the outer part of the corpus callosum and transcallosal bilateral hemispheres on MRI, even though inner callosal lesions are common in multiple sclerosis.

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

Science.gov (United States)

Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mechanisms and neuronal networks involved in reactive and proactive cognitive control of interference in working memory.

Science.gov (United States)

Irlbacher, Kerstin; Kraft, Antje; Kehrer, Stefanie; Brandt, Stephan A

2014-10-01

Cognitive control can be reactive or proactive in nature. Reactive control mechanisms, which support the resolution of interference, start after its onset. Conversely, proactive control involves the anticipation and prevention of interference prior to its occurrence. The interrelation of both types of cognitive control is currently under debate: Are they mediated by different neuronal networks? Or are there neuronal structures that have the potential to act in a proactive as well as in a reactive manner? This review illustrates the way in which integrating knowledge gathered from behavioral studies, functional imaging, and human electroencephalography proves useful in answering these questions. We focus on studies that investigate interference resolution at the level of working memory representations. In summary, different mechanisms are instrumental in supporting reactive and proactive control. Distinct neuronal networks are involved, though some brain regions, especially pre-SMA, possess functions that are relevant to both control modes. Therefore, activation of these brain areas could be observed in reactive, as well as proactive control, but at different times during information processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

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Ding, Song-Ze, E-mail: dingsongze@hotmail.com [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Yang, Yu-Xiu; Li, Xiu-Ling [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Michelli-Rivera, Audrey [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Han, Shuang-Yin [Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China); Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J. [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

2013-05-15

Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and

Multiple complexes of nitrogen assimilatory enzymes in spinach chloroplasts: possible mechanisms for the regulation of enzyme function.

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Yoko Kimata-Ariga

Full Text Available Assimilation of nitrogen is an essential biological process for plant growth and productivity. Here we show that three chloroplast enzymes involved in nitrogen assimilation, glutamate synthase (GOGAT, nitrite reductase (NiR and glutamine synthetase (GS, separately assemble into distinct protein complexes in spinach chloroplasts, as analyzed by western blots under blue native electrophoresis (BN-PAGE. GOGAT and NiR were present not only as monomers, but also as novel complexes with a discrete size (730 kDa and multiple sizes (>120 kDa, respectively, in the stromal fraction of chloroplasts. These complexes showed the same mobility as each monomer on two-dimensional (2D SDS-PAGE after BN-PAGE. The 730 kDa complex containing GOGAT dissociated into monomers, and multiple complexes of NiR reversibly converted into monomers, in response to the changes in the pH of the stromal solvent. On the other hand, the bands detected by anti-GS antibody were present not only in stroma as a conventional decameric holoenzyme complex of 420 kDa, but also in thylakoids as a novel complex of 560 kDa. The polypeptide in the 560 kDa complex showed slower mobility than that of the 420 kDa complex on the 2D SDS-PAGE, implying the assembly of distinct GS isoforms or a post-translational modification of the same GS protein. The function of these multiple complexes was evaluated by in-gel GS activity under native conditions and by the binding ability of NiR and GOGAT with their physiological electron donor, ferredoxin. The results indicate that these multiplicities in size and localization of the three nitrogen assimilatory enzymes may be involved in the physiological regulation of their enzyme function, in a similar way as recently described cases of carbon assimilatory enzymes.

Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

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Tobias Ruck

2015-07-01

Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

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Urue?a, Claudia; Cifuentes, Claudia; Casta?eda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

2008-01-01

Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytosk...

Mechanism(s) involved in opioid drug abuse modulation of HAND.

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Dutta, Raini; Roy, Sabita

2012-07-01

Drug abuse and HIV infection are interlinked. From the onset of the HIV/AIDS epidemic, the impact of illicit drug use on HIV disease progression has been a focus of many investigations. Both laboratory-based and epidemiological studies strongly indicate that drug abuse may exacerbate HIV disease progression and increase mortality and morbidity in these patients. Increase susceptibility to opportunistic infection has been implicated as one of the major causes for this detriment. Furthermore, opioids are known to elicit prevalence of neurodegenerative disorders in HIV-infected patients. Numerous authors have delineated various molecular as well as cellular mechanisms associated with neurological complications in these patients. This review gives an overview of these findings. Understanding the mechanisms will allow for the development of targeted therapies aimed at reducing the progression of neurocognitive decline in the drug abusing HIV infected individuals.

Multiple sclerosis: Pregnancy and women's health issues.

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Mendibe Bilbao, M; Boyero Durán, S; Bárcena Llona, J; Rodriguez-Antigüedad, A

2016-08-18

The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. To analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease. We conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for 'multiple sclerosis', 'MS', 'EAE', 'pregnancy', 'hormonal factors', 'treatment', and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts. We provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, fetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

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Scott Cukras

Full Text Available Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

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Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

2014-01-01

Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

Specificity and multiplicity in the recognition of individuals: implications for the evolution of social behaviour.

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Wiley, R H

2013-02-01

Recognition of conspecifics occurs when individuals classify sets of conspecifics based on sensory input from them and associate these sets with different responses. Classification of conspecifics can vary in specificity (the number of individuals included in a set) and multiplicity (the number of sets differentiated). In other words, the information transmitted varies in complexity. Although recognition of conspecifics has been reported in a wide variety of organisms, few reports have addressed the specificity or multiplicity of this capability. This review discusses examples of these patterns, the mechanisms that can produce them, and the evolution of these mechanisms. Individual recognition is one end of a spectrum of specificity, and binary classification of conspecifics is one end of a spectrum of multiplicity. In some cases, recognition requires no more than simple forms of learning, such as habituation, yet results in individually specific recognition. In other cases, recognition of individuals involves complex associations of multiple cues with multiple previous experiences in particular contexts. Complex mechanisms for recognition are expected to evolve only when simpler mechanisms do not provide sufficient specificity and multiplicity to obtain the available advantages. In particular, the evolution of cooperation and deception is always promoted by specificity and multiplicity in recognition. Nevertheless, there is only one demonstration that recognition of specific individuals contributes to cooperation in animals other than primates. Human capacities for individual recognition probably have a central role in the evolution of complex forms of human cooperation and deception. Although relatively little studied, this capability probably rivals cognitive abilities for language. © 2012 The Author. Biological Reviews © 2012 Cambridge Philosophical Society.

A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

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Andrew P. Wojtovich

2013-03-01

Full Text Available Opening of BK-type Ca2+ activated K+ channels protects the heart against ischemia-reperfusion (IR injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats.

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Lozano-Cuenca, J; González-Hernández, A; López-Canales, O A; Villagrana-Zesati, J R; Rodríguez-Choreão, J D; Morín-Zaragoza, R; Castillo-Henkel, E F; López-Canales, J S

2017-08-07

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (Pclobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability.

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Jasse, Laurence; Vukusic, Sandra; Durand-Dubief, Françoise; Vartin, Cristina; Piras, Carolina; Bernard, Martine; Pélisson, Denis; Confavreux, Christian; Vighetto, Alain; Tilikete, Caroline

2013-10-01

The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs). Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25). PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests. Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.

Dual mechanisms regulating glutamate decarboxylases and accumulation of gamma-aminobutyric acid in tea (Camellia sinensis) leaves exposed to multiple stresses.

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Mei, Xin; Chen, Yiyong; Zhang, Lingyun; Fu, Xiumin; Wei, Qing; Grierson, Don; Zhou, Ying; Huang, Yahui; Dong, Fang; Yang, Ziyin

2016-03-29

γ-Aminobutyric acid (GABA) is one of the major inhibitory neurotransmitters in the central nervous system. It has multiple positive effects on mammalian physiology and is an important bioactive component of tea (Camellia sinensis). GABA generally occurs at a very low level in plants but GABA content increases substantially after exposure to a range of stresses, especially oxygen-deficiency. During processing of tea leaves, a combination of anoxic stress and mechanical damage are essential for the high accumulation of GABA. This is believed to be initiated by a change in glutamate decarboxylase activity, but the underlying mechanisms are unclear. In the present study we characterized factors regulating the expression and activity of three tea glutamate decarboxylase genes (CsGAD1, 2, and 3), and their encoded enzymes. The results suggests that, unlike the model plant Arabidopsis thaliana, there are dual mechanisms regulating the accumulation of GABA in tea leaves exposed to multiple stresses, including activation of CsGAD1 enzymatic activity by calmodulin upon the onset of the stress and accumulation of high levels of CsGAD2 mRNA induced by a combination of anoxic stress and mechanical damage.

Acoustic emission generated by dislocation mechanisms during the deformation of metals

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Heiple, C.R.

1978-01-01

Acoustic emission is a transient elastic wave generated by the rapid release of energy within a material. A wide variety of mechanisms have been proposed as possible sources of acoustic emission. Proposed mechanisms have included crack propagation, precipitate fracture, twin formation, martensite formation, dislocation motion and/or multiplication. This paper is concerned with acoustic emission generated by dislocation mechanisms operating during plastic deformation. Twinning and martensitic phase transformations are excluded even though dislocation motion is involved in the nucleation and growth of twins and the growth of martensite

Acoustic emission generated by dislocation mechanisms during the deformation of metals

Energy Technology Data Exchange (ETDEWEB)

Heiple, C.R.

1978-01-01

Acoustic emission is a transient elastic wave generated by the rapid release of energy within a material. A wide variety of mechanisms have been proposed as possible sources of acoustic emission. Proposed mechanisms have included crack propagation, precipitate fracture, twin formation, martensite formation, dislocation motion and/or multiplication. This paper is concerned with acoustic emission generated by dislocation mechanisms operating during plastic deformation. Twinning and martensitic phase transformations are excluded even though dislocation motion is involved in the nucleation and growth of twins and the growth of martensite.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

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Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas

A perspective on multiple waves of influenza pandemics.

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Mummert, Anna; Weiss, Howard; Long, Li-Ping; Amigó, José M; Wan, Xiu-Feng

2013-01-01

A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies. We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where each wave spreads through one sub-population. The fourth mechanism is virus mutation which causes delayed susceptibility of individuals. The fifth mechanism is waning immunity. Each mechanism is incorporated into separate mathematical models, and outbreaks are then simulated. We use the models to examine the effects of the initial number of infected individuals (e.g., border control at the beginning of the outbreak) and the timing of and amount of available vaccinations. Four models, individually or in any combination, reproduce the two waves of the 2009 H1N1 pandemic in the United States, both qualitatively and quantitatively. One model reproduces the two waves only qualitatively. All models indicate that significantly reducing or delaying the initial numbers of infected individuals would have little impact on the attack rate. Instead, this reduction or delay results in a single wave as opposed to two waves. Furthermore, four of these models also indicate that a vaccination program started earlier than October 2009 (when the H1N1 vaccine was initially distributed) could have eliminated the second wave of infection, while more vaccine available starting in October would not have eliminated the second wave.

A perspective on multiple waves of influenza pandemics.

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Anna Mummert

Full Text Available A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies.We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography, where each wave spreads through one sub-population. The fourth mechanism is virus mutation which causes delayed susceptibility of individuals. The fifth mechanism is waning immunity. Each mechanism is incorporated into separate mathematical models, and outbreaks are then simulated. We use the models to examine the effects of the initial number of infected individuals (e.g., border control at the beginning of the outbreak and the timing of and amount of available vaccinations.Four models, individually or in any combination, reproduce the two waves of the 2009 H1N1 pandemic in the United States, both qualitatively and quantitatively. One model reproduces the two waves only qualitatively. All models indicate that significantly reducing or delaying the initial numbers of infected individuals would have little impact on the attack rate. Instead, this reduction or delay results in a single wave as opposed to two waves. Furthermore, four of these models also indicate that a vaccination program started earlier than October 2009 (when the H1N1 vaccine was initially distributed could have eliminated the second wave of infection, while more vaccine available starting in October would not have eliminated the second wave.

Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

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Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

2008-09-01

Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

Mechanisms of behavior modification in clinical behavioral medicine in China.

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

2014-08-01

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

Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved

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M. H. Mohd. Sani

2012-01-01

Full Text Available Muntingia calabura L. (family Elaeocarpaceae has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test and thermal (hot plate test models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05 antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO donor, NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS, methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP pathway, or their combination also caused significant (P<0.05 change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

Structure-function relations in physiology education: Where's the mechanism?

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Lira, Matthew E; Gardner, Stephanie M

2017-06-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such as structure-function relations, selectively neglect mechanisms by not mentioning this term explicitly. We explored how students characterized mechanisms and functions to shed light on how students make sense of these terms. Students characterized mechanisms as 1 ) processes that occur at levels of organization lower than that of functions; and 2 ) as detailed events with many steps involved. We also found that students produced more variability in how they characterized functions compared with mechanisms: students characterized functions in relation to multiple levels of organization and multiple definitions. We interpret these results as evidence that students see mechanisms as holding a more narrow definition than used in the biological sciences, and that students struggle to coordinate and distinguish mechanisms from functions due to cognitive processes germane to learning in many domains. We offer the instructional suggestion that we scaffold student learning by affording students opportunities to relate and also distinguish between these terms so central to understanding physiology. Copyright © 2017 the American Physiological Society.

Teaching and Evaluation Materials Utilizing Multiple Representations in Mechanics

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Savinainen, A.; Nieminen, P.; Makynen, A.; Viiri, J.

2013-01-01

In this paper, we present materials and teaching ideas utilizing multiple representations in the contexts of kinematics and the force concept. These ideas and materials are substantiated by evidence and can be readily used in teaching with no special training. In addition, we briefly discuss two multiple-choice tests based on physics education…

Multiple non-syndromic odontogenic keratocysts in three siblings

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Nirwan, Amit; Wanjari, Sangeeta Panjab; Saikhedkar, Rashmi; Karun, Vinayak

2013-01-01

Occurrence of multiple cysts (MC) involving the jaw is rare. When multiple, it is usually associated with a syndrome. Occurrence of MC without syndromic association is extremely rare. Multiple odontogenic cysts mostly could be odontogenic keratocysts or dentigerous cysts. Odontogenic keratocyst shows involvement of mandible over maxilla, with peak incidence in second and third decade and it is exceedingly rare before 10 years of age. However multiple odontogenic keratocysts found in children are often reflective of nevoid basal cell carcinoma syndrome. Here is a case report which documents multiple jaw cysts involving both the jaws, in three siblings of ages 10, 13 and 17 years with negative parental history. All three reported cases were free of any systemic involvement. As odontogenic keratocyst spreads through bone marrow, destruction is more before any clinical manifestation. Therefore, early detection and intervention are essential in preventing extensive destruction. PMID:23505078

Simultaneous Measurement of Multiple Mechanical Properties of Single Cells Using AFM by Indentation and Vibration.

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Zhang, Chuang; Shi, Jialin; Wang, Wenxue; Xi, Ning; Wang, Yuechao; Liu, Lianqing

2017-12-01

The mechanical properties of cells, which are the main characteristics determining their physical performance and physiological functions, have been actively studied in the fields of cytobiology and biomedical engineering and for the development of medicines. In this study, an indentation-vibration-based method is proposed to simultaneously measure the mechanical properties of cells in situ, including cellular mass (m), elasticity (k), and viscosity (c). The proposed measurement method is implemented based on the principle of forced vibration stimulated by simple harmonic force using an atomic force microscope (AFM) system integrated with a piezoelectric transducer as the substrate vibrator. The corresponding theoretical model containing the three mechanical properties is derived and used to perform simulations and calculations. Living and fixed human embryonic kidney 293 (HEK 293) cells were subjected to indentation and vibration to measure and compare their mechanical parameters and verify the proposed approach. The results that the fixed sample cells are more viscous and elastic than the living sample cells and the measured mechanical properties of cell are consistent within, but not outside of the central region of the cell, are in accordance with the previous studies. This work provides an approach to simultaneous measurement of the multiple mechanical properties of single cells using an integrated AFM system based on the principle force vibration and thickness-corrected Hertz model. This study should contribute to progress in biomedical engineering, cytobiology, medicine, early diagnosis, specific therapy and cell-powered robots.

Multiple proteins of White spot syndrome virus involved in ...

Indian Academy of Sciences (India)

2014-03-20

Mar 20, 2014 ... β-integrin with structure proteins of WSSV and motifs involved in WSSV infection was examined. The results showed ... Introduction. White spot ... denatured conditions and renatured by successive 12 h incu- bations with 6, 4, ...

Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

Directory of Open Access Journals (Sweden)

Amy ePerrin Ross

2013-03-01

Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

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Zhara M Hatami

2016-02-01

Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

An Approach to Implementing A Threshold Adjusting Mechanism in Very Complex Negotiations : A Preliminary Result

OpenAIRE

Fujita, Katsuhide; Ito, Takayuki; Hattori, Hiromitsu; Klein, Mark

2007-01-01

In this paper, we propose a threshold adjusting mechanism in very complex negotiations among software agents. The proposed mechanism can facilitate agents to reach an agreement while keeping their private information as much as possible. Multi-issue negotiation protocols have been studied widely and represent a promising field since most negotiation problems in the real world involve interdependent multiple issues. We have proposed negotiation protocols where a bidding-based mechanism is used...

Multiple Beneficial Health Effects of Natural Alkylglycerols from Shark Liver Oil

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Alain B. Legrand

2010-07-01

Full Text Available Alkylglycerols (alkyl-Gro are ether lipids abundant in the liver of some elasmobranch fish species such as ratfishes and some sharks. Shark liver oil from Centrophorus squamosus (SLO, or alkyl-Gro mix from this source, have several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, or anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids, and lipid signaling interactions. Natural alkyl-Gro mix from SLO contains several alkyl-Gro, varying by chain length and unsaturation. Six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro, were synthesized and tested for anti-tumor and anti-metastatic activities on a model of grafted tumor in mice (3LL cells. 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0 or no (12:0, 14:0, 18:0 effect. Multiple compounds and mechanisms are probably involved in the multiple activities of natural alkyl-Gro.

Effect of multiple forming tools on geometrical and mechanical properties in incremental sheet forming

Science.gov (United States)

Wernicke, S.; Dang, T.; Gies, S.; Tekkaya, A. E.

2018-05-01

The tendency to a higher variety of products requires economical manufacturing processes suitable for the production of prototypes and small batches. In the case of complex hollow-shaped parts, single point incremental forming (SPIF) represents a highly flexible process. The flexibility of this process comes along with a very long process time. To decrease the process time, a new incremental forming approach with multiple forming tools is investigated. The influence of two incremental forming tools on the resulting mechanical and geometrical component properties compared to SPIF is presented. Sheets made of EN AW-1050A were formed to frustums of a pyramid using different tool-path strategies. Furthermore, several variations of the tool-path strategy are analyzed. A time saving between 40% and 60% was observed depending on the tool-path and the radii of the forming tools while the mechanical properties remained unchanged. This knowledge can increase the cost efficiency of incremental forming processes.

Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation

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Gunzburg Robert

2006-04-01

Full Text Available Abstract Background Spinal manipulation has been found to create demonstrable segmental and intersegmental spinal motions thought to be biomechanically related to its mechanisms. In the case of impulsive-type instrument device comparisons, significant differences in the force-time characteristics and concomitant motion responses of spinal manipulative instruments have been reported, but studies investigating the response to multiple thrusts (multiple impulse trains have not been conducted. The purpose of this study was to determine multi-axial segmental and intersegmental motion responses of ovine lumbar vertebrae to single impulse and multiple impulse spinal manipulative thrusts (SMTs. Methods Fifteen adolescent Merino sheep were examined. Tri-axial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under fluoroscopic guidance while the animals were anesthetized. A hand-held electromechanical chiropractic adjusting instrument (Impulse was used to apply single and repeated force impulses (13 total over a 2.5 second time interval at three different force settings (low, medium, and high along the posteroanterior axis of the T12 spinous process. Axial (AX, posteroanterior (PA, and medial-lateral (ML acceleration responses in adjacent segments (L1, L2 were recorded at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2 and intersegmental acceleration transfer (L1–L2 for each axis and each force setting were computed from the acceleration-time recordings. The initial acceleration response for a single thrust and the maximum acceleration response observed during the 12 multiple impulse trains were compared using a paired observations t-test (POTT, alpha = .05. Results Segmental and intersegmental acceleration responses mirrored the peak force magnitude produced by the Impulse Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes. Compared to

Multi-physics modeling of single/multiple-track defect mechanisms in electron beam selective melting

International Nuclear Information System (INIS)

Yan, Wentao; Ge, Wenjun; Qian, Ya; Lin, Stephen; Zhou, Bin; Liu, Wing Kam; Lin, Feng; Wagner, Gregory J.

2017-01-01

Metallic powder bed-based additive manufacturing technologies have many promising attributes. The single track acts as one fundamental building unit, which largely influences the final product quality such as the surface roughness and dimensional accuracy. A high-fidelity powder-scale model is developed to predict the detailed formation processes of single/multiple-track defects, including the balling effect, single track nonuniformity and inter-track voids. These processes are difficult to observe in experiments; previous studies have proposed different or even conflicting explanations. Our study clarifies the underlying formation mechanisms, reveals the influence of key factors, and guides the improvement of fabrication quality of single tracks. Additionally, the manufacturing processes of multiple tracks along S/Z-shaped scan paths with various hatching distance are simulated to further understand the defects in complex structures. The simulations demonstrate that the hatching distance should be no larger than the width of the remelted region within the substrate rather than the width of the melted region within the powder layer. Thus, single track simulations can provide valuable insight for complex structures.

An ultrafast spectroscopic and quantum mechanical investigation of multiple emissions in push-pull pyridinium derivatives bearing different electron donors.

Science.gov (United States)

Carlotti, B; Benassi, E; Cesaretti, A; Fortuna, C G; Spalletti, A; Barone, V; Elisei, F

2015-08-28

A joint experimental and theoretical approach, involving state-of-the-art femtosecond fluorescence up-conversion measurements and quantum mechanical computations including vibronic effects, was employed to get a deep insight into the excited state dynamics of two cationic dipolar chromophores (Donor-π-Acceptor(+)) where the electron deficient portion is a N-methyl pyridinium and the electron donor a trimethoxyphenyl or a pyrene, respectively. The ultrafast spectroscopic investigation, and the time resolved area normalised emission spectra in particular, revealed a peculiar multiple emissive behaviour and allowed the distinct emitting states to be remarkably distinguished from solvation dynamics, occurring in water in a similar timescale. The two and three emissions experimentally detected for the trimethoxyphenyl and pyrene derivatives, respectively, were associated with specific local emissive minima in the potential energy surface of S1 on the ground of quantum-mechanical calculations. A low polar and planar Locally Excited (LE) state together with a highly polar and Twisted Intramolecular Charge Transfer (TICT) state is identified to be responsible for the dual emission of the trimethoxyphenyl compound. Interestingly, the more complex photobehaviour of the pyrenyl derivative was explained considering the contribution to the fluorescence coming not only from the LE and TICT states but also from a nearly Planar Intramolecular Charge Transfer (PICT) state, with both the TICT and the PICT generated from LE by progressive torsion around the quasi-single bond between the methylpyridinium and the ethene bridge. These findings point to an interconversion between rotamers for the pyrene compound taking place in its excited state against the Non-equilibrated Excited Rotamers (NEER) principle.

The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

Science.gov (United States)

Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

2011-01-01

Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

Does mechanism of drug action matter to inform rational polytherapy in epilepsy?

Science.gov (United States)

Giussani, Giorgia; Beghi, Ettore

2013-05-01

When monotherapy for epilepsy fails, add-on therapy is an alternative option. There are several possible antiepileptic drug combinations based on their different and multiple mechanisms of action and pharmacokinetic interactions. However, only when benefits of drug combinations outweigh the harms, polytherapy can be defined as "rational". In the past 20 years, second generation AEDs have been marketed, some of which have better defined mechanisms of action and better pharmacokinetic profile. The mechanisms of action of AEDs involve, among others, blockade of voltage-gated sodium channels, blockade of voltage-gated calcium channel, activation of the ionotropic GABAA receptor and increase of GABA levels at the synaptic cleft, blockade of glutamate receptors, binding to synaptic vesicle protein 2A, and opening of KCNQ (Kv7) potassium channels. Aim of this review was to examine published reports on AEDs combinations in animal models and humans focusing on mechanisms of action and pharmacokinetic interactions. Studies in animals have shown that AED combinations are more effective when using drugs with different mechanisms of action. The most effective combination was found using a drug with a single mechanism of action and another with multiple mechanisms of action. In humans some combinations between a blocker of voltage-gated sodium channels and a drug with multiple mechanisms of action may be synergistic. Future studies are necessary to better define rational combinations and complementary mechanisms of action, considering also pharmacokinetic interactions and measures of toxicity and not only drug efficacy.

A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

Directory of Open Access Journals (Sweden)

Chen Xie

Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

Multiple homicides.

Science.gov (United States)

Copeland, A R

1989-09-01

A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

Epigenetic changes in neurology: DNA methylation in multiple sclerosis.

Science.gov (United States)

Iridoy Zulet, M; Pulido Fontes, L; Ayuso Blanco, T; Lacruz Bescos, F; Mendioroz Iriarte, M

2017-09-01

Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

公安机关参与的矛盾纠纷多元解决机制的构建%On the Construction of Public Security Organs Involved Conflicts and Disputes Multiple Solution Mechanism

Institute of Scientific and Technical Information of China (English)

俞利平; 任继升

2013-01-01

The construction of conflicts and disputes multiple solution mechanism is a common subject facing all the countries in the aspects of disputes solution and judicial system development .Solving social conflicts and disputes is a major research subject for current public security organs .This paper analyzes the role and function of public security organs in solving conflicts and disputes based on the relevant theories , points out the difficulties fa-cing public security organs in solving conflicts and disputes and put forwards some proposals as to the construction of a multiple solution mechanism .%矛盾纠纷多元解决机制是当今世界各国在纠纷解决和司法制度发展中面临的共同课题，化解社会矛盾纠纷，则成为公安机关现阶段的一个重要研究课题。以新时期公安机关参与矛盾纠纷多元解决机制的理论基础为依据，分析公安机关在化解矛盾纠纷多元机制中的主体地位和作用，找出公安机关在化解矛盾纠纷多元机制中的困境，提出完善公安机关化解矛盾纠纷多元机制的建议。

Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

Science.gov (United States)

Fujita, Masahide; Andoh, Tsugunobu; Saiki, Ikuo; Kuraishi, Yasushi

2008-02-01

We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but not the ET(B)-receptor antagonist BQ-788 (1 and 3 nmol/site), inhibited mechanical allodynia in mice with grown melanoma. In naive mice, an intraplantar injection of tumor extract (1 and 3 mg/site), which was prepared from the grown melanoma in the paw, produced mechanical allodynia, which was inhibited by BQ-123 and BQ-788 at doses of 3 and 10 nmol/site. An intraplantar injection of ET-1 (1 and 10 pmol/site) elicited licking behavior, which was increased in the melanoma-bearing hind paw. BQ-123 (3 and 10 nmol/site) inhibited licking induced by ET-1 (10 pmol/site). The level of mRNA of ET(A), but not ET(B), receptor, was significantly increased in the dorsal root ganglia on the inoculated side. Cultured B16-BL6 cells contained ET, and the melanoma mass increased the concentration of ET as it grew bigger. These results suggest that ET-1 and ET(A) receptor are at least partly involved in the induction of pain induced by melanoma cell inoculation.

Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

International Nuclear Information System (INIS)

Kaneuji, Takeshi; Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro; Takahashi, Tetsu; Nishihara, Tatsuji

2011-01-01

Highlights: → Effect of compressive force on osteoblasts were examined. → Compressive force induced OPG expression and suppressed osteoclastogenesis. → This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm 2 ) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-κB ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of IκBα, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca 2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-κB) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca 2+ pathway.

Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

Energy Technology Data Exchange (ETDEWEB)

Kaneuji, Takeshi [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori; Toshinaga, Akihiro [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Takahashi, Tetsu [Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu 803-8580 (Japan)

2011-04-29

Highlights: {yields} Effect of compressive force on osteoblasts were examined. {yields} Compressive force induced OPG expression and suppressed osteoclastogenesis. {yields} This enhancement of OPG is dependent on Wnt/Ca2+ signal pathway. -- Abstract: Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm{sup 2}) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-{kappa}B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I{kappa}B{alpha}, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca{sup 2+} pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL. Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-{kappa}B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt

IDEA and Family Involvement

Directory of Open Access Journals (Sweden)

Mehmet Emin Öztürk

2017-01-01

Full Text Available Individuals with Disabilities Education Act (IDEA gives many rights to parents with special needs in terms of involvement and participation. Given the importance of family involvement in the special education process, and federal legislation that increasingly mandated and supported such involvement over time, considerable research has focused on the multiple ways that relationships between schools and families in the special education decision making process have played out. Educational professionals should create a positive climate for CLD families so that they feel more comfortable and therefore are able to participate more authentically and meaningfully.

Visualization of a City Sustainability Index (CSI: Towards Transdisciplinary Approaches Involving Multiple Stakeholders

Directory of Open Access Journals (Sweden)

Koichiro Mori

2015-09-01

Full Text Available We have developed a visualized 3-D model of a City Sustainability Index (CSI based on our original concept of city sustainability in which a sustainable city is defined as one that maximizes socio-economic benefits while meeting constraint conditions of the environment and socio-economic equity on a permanent basis. The CSI is based on constraint and maximization indicators. Constraint indicators assess whether a city meets the necessary minimum conditions for city sustainability. Maximization indicators measure the benefits that a city generates in socio-economic aspects. When used in the policy-making process, the choice of constraint indicators should be implemented using a top-down approach. In contrast, a bottom-up approach is more suitable for defining maximization indicators because this technique involves multiple stakeholders (in a transdisciplinary approach. Using different materials of various colors, shapes, sizes, we designed and constructed the visualized physical model of the CSI to help people evaluate and compare the performance of different cities in terms of sustainability. The visualized model of the CSI can convey complicated information in a simple and straightforward manner to diverse stakeholders so that the sustainability analysis can be understood intuitively by ordinary citizens as well as experts. Thus, the CSI model helps stakeholders to develop critical thinking about city sustainability and enables policymakers to make informed decisions for sustainability through a transdisciplinary approach.

Study on the mechanism of seepage flow in the grouting for multiple fractured model

International Nuclear Information System (INIS)

Nishigaki, Makoto; Mikake, Shin-ichiro

2002-01-01

The purpose of study is to improve the grouting method for fractured rock masses. In this paper, the results on the fundamental phenomenon for grasping the properties of grouting injection and seepage flow are discussed. The case of grouting stage is studied about the multiple hydraulic fractured apertures in the injected borehole. So the theory on the mechanism is constructed, and experiment is executed in order to verify the availability of the theory. From the results, it is shown that Bernoulli's law is able to prove the behavior of the grouting. And the theoretical evaluation is executed on the experiential procedure of the grouting. (author)

Mechanism of chimera formation during the Multiple Displacement Amplification reaction

Directory of Open Access Journals (Sweden)

Stockwell Timothy B

2007-04-01

Full Text Available Abstract Background Multiple Displacement Amplification (MDA is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

Science.gov (United States)

Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

Gravity alterations are widely recognized to influence living systems. They may cause temporary or permanent effects on physiology and development at different levels, from gene expression to morphogenesis. However, the molecular mechanisms underlying these effects are often unclear, and adequate model systems to study them are required. To address this problem we developed a new experimental model of how gravity affects morphogenesis during tail regeneration in the newt Pleurodeles waltl. The effects of increased gravity on newt tail morphogenesis were first documented in two joint Russian-US NASA spaceflight experiments in the Russian Foton-M2 (2005) and Foton-M3 (2007) missions. In these experiments the shape of newt tail regenerate was found to depend on the gravity level, being dorso-ventrally symmetrical in microgravity and in neutrally-buoyant aquarium controls, versus hook-like and bent downward in 1g controls. These 1g controls were conducted in spaceflight habitats using a water-saturated PVA sponge mat. These results were reproducible in multiple spaceflight, and ground laboratory studies, both in the US at NASA ARC and in Russia at IDB RAS, and were characterized in detail using morphometry and histology approaches. The role of hypergravity in shaping morphogenesis was confirmed at NASA ARC with an experiment in the ISS Testbed 8-foot diameter centrifuge operating at 2g. Animals that experienced two-week centrifugation (the period of time used in the Foton flights) developed the same hook-like regenerates as 1g controls, and morphometric analysis revealed no significant difference between 1g and 2g groups, however both were significantly different from aquarium controls. We hypothesize that exposure to 1g or 2g during tail morphogenesis constitutes excessive loading for newts that are adapted to microgravity-like conditions in their aquatic habitat. Because Heat Shock Proteins (HSPs) are stress-induced molecules that respond to a broad variety of

Generalization of Wilemski-Fixman-Weiss decoupling approximation to the case involving multiple sinks of different sizes, shapes, and reactivities.

Science.gov (United States)

Uhm, Jesik; Lee, Jinuk; Eun, Changsun; Lee, Sangyoub

2006-08-07

We generalize the Wilemski-Fixman-Weiss decoupling approximation to calculate the transient rate of absorption of point particles into multiple sinks of different sizes, shapes, and reactivities. As an application we consider the case involving two spherical sinks. We obtain a Laplace-transform expression for the transient rate that is in excellent agreement with computer simulations. The long-time steady-state rate has a relatively simple expression, which clearly shows the dependence on the diffusion constant of the particles and on the sizes and reactivities of sinks, and its numerical result is in good agreement with the known exact result that is given in terms of recursion relations.

Mechanisms Involved in Nematode Control by Endophytic Fungi.

Science.gov (United States)

Schouten, Alexander

2016-08-04

Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood but most likely multifactorial. This knowledge gap obstructs the progress regarding the development of endophytes or endophyte-derived constituents into biocontrol agents. In part, this may be caused by the fact that endophytic fungi form a rather heterogeneous group. By combining the knowledge of the currently characterized antagonistic endophytic fungi and their effects on nematode behavior and biology with the knowledge of microbial competition and induced plant defenses, the various mechanisms by which this nematode antagonism operates or may operate are discussed. Now that new technologies are becoming available and more accessible, the currently unresolved mechanisms can be studied in greater detail than ever before.

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

Science.gov (United States)

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

General mechanism involved in subwavelength optics of conducting microstructures: charge-oscillation-induced light emission and interference.

Science.gov (United States)

Huang, Xian-Rong; Peng, Ru-Wen

2010-04-01

Interactions between light and conducting microstructures or nanostructures can result in a variety of novel phenomena, but their underlying mechanisms have not been completely understood. From calculations of surface charge density waves on conducting gratings and by comparing them with classical surface plasmons, we revealed a general yet concrete picture regarding the coupling of light to free electron oscillation on structured conducting surfaces that can lead to oscillating subwavelength charge patterns (i.e., structured surface plasmons). New wavelets emitted from these light sources then destructively interfere to form evanescent waves. This principle, usually combined with other mechanisms, is mainly a geometrical effect that can be universally involved in light scattering from all periodic and non-periodic structures containing free electrons. This picture may provide clear guidelines for developing conductor-based nano-optical devices.

Tc-99m MIBI imaging for secondary skeletal involvement in breast and prostate cancers and multiple myeloma

International Nuclear Information System (INIS)

Zehra, F.; Haq, S.; Fatmi, S.; Safaqat, S.

2004-01-01

Objective:The Objective of the study was to evaluate the role of Tc-99m MIBI whole body imaging in assessing secondary osseous involvement in patients with malignancy of breast, prostate or multiple myeloma. In this study a total of 41 patients were included. Out of these 18 had breast carcinoma, 12 had prostate carcinoma and 11 were diagnosed cases of multiple myeloma. All patients had their whole body MIBI imaging done which was compared with MDP bone scan by employing some other diagnostic modality (plain radiographs, CT scan, MRI scan or histopathological evidence) to confirm the lesions detected by either of the scans. The results of all the studies were evaluated qualitatively by assessing the number of lesions visually by three experienced nuclear physicians. Quantitative analysis of the lesions was also done, by calculating the lesion to normal uptake ratio, to augment the findings of visual assessment and for statistical analysis. Results: Results obtained in this study by MIBI and MDP imaging varied significantly among different groups and subgroups of patients depending on the primary malignancy and stage of therapy. However results obtained by imaging of patients within a group and subgroup were consistent with each other. MIBI scan showed a sensitivity of 99% in cases of multiple myeloma, where MDP scan was only 16% sensitive. In case of pre-therapy patients of breast and prostate carcinoma, the sensitivity of MIBI scan came out to be 80% and 74% respectively. In patients who were on chemo/radiotherapy MIBI scan was 54% sensitive in patients with breast carcinoma and 38% sensitive in patients with prostate carcinoma. MDP scan showed a sensitivity of 100% in all the groups. The positive predictive value of MIBI scan came out to be 100% but that of MDP was 42-76% in different groups. It is therefore concluded that the most significant role of MIBI imaging is in detection of bone metastases secondary to breast and prostate carcinoma in pre

Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

Science.gov (United States)

Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

2014-07-07

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway.

Science.gov (United States)

Sato, Yukuto; Hashiguchi, Yasuyuki; Nishida, Mutsumi

2009-02-20

Duplicate genes are considered to have evolved through the partitioning of ancestral functions among duplicates (subfunctionalization) and/or the acquisition of novel functions from a beneficial mutation (neofunctionalization). Additionally, an increase in gene dosage resulting from duplication may also confer an advantageous effect, as has been suggested for histone, tRNA, and rRNA genes. Currently, there is little understanding of the effect of increased gene dosage on subcellular networks like signal transduction pathways. Addressing this issue may provide further insights into the evolution by gene duplication. We analyzed the evolution of multiple stickleback phosphodiesterase (PDE, EC: 3.1.4.17) 1C genes involved in the cyclic nucleotide signaling pathway. Stickleback has 8-9 copies of this gene, whereas only one or two loci exist in other model vertebrates. Our phylogenetic and synteny analyses suggested that the multiple PDE1C genes in stickleback were generated by repeated duplications of >100-kbp chromosome segments. Sequence evolution analysis did not provide strong evidence for neofunctionalization in the coding sequences of stickleback PDE1C isoforms. On the other hand, gene expression analysis suggested that the derived isoforms acquired expression in new organs, implying their neofunctionalization in terms of expression patterns. In addition, at least seven isoforms of the stickleback PDE1C were co-expressed with olfactory-type G-proteins in the nose, suggesting that PDE1C dosage is increased in the stickleback olfactory transduction (OT) pathway. In silico simulations of OT implied that the increased PDE1C dosage extends the longevity of the depolarization signals of the olfactory receptor neuron. The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our analyses imply that an increase in gene product sometimes

Evolution of multiple phosphodiesterase isoforms in stickleback involved in cAMP signal transduction pathway

Directory of Open Access Journals (Sweden)

Nishida Mutsumi

2009-02-01

Full Text Available Abstract Background Duplicate genes are considered to have evolved through the partitioning of ancestral functions among duplicates (subfunctionalization and/or the acquisition of novel functions from a beneficial mutation (neofunctionalization. Additionally, an increase in gene dosage resulting from duplication may also confer an advantageous effect, as has been suggested for histone, tRNA, and rRNA genes. Currently, there is little understanding of the effect of increased gene dosage on subcellular networks like signal transduction pathways. Addressing this issue may provide further insights into the evolution by gene duplication. Results We analyzed the evolution of multiple stickleback phosphodiesterase (PDE, EC: 3.1.4.17 1C genes involved in the cyclic nucleotide signaling pathway. Stickleback has 8–9 copies of this gene, whereas only one or two loci exist in other model vertebrates. Our phylogenetic and synteny analyses suggested that the multiple PDE1C genes in stickleback were generated by repeated duplications of >100-kbp chromosome segments. Sequence evolution analysis did not provide strong evidence for neofunctionalization in the coding sequences of stickleback PDE1C isoforms. On the other hand, gene expression analysis suggested that the derived isoforms acquired expression in new organs, implying their neofunctionalization in terms of expression patterns. In addition, at least seven isoforms of the stickleback PDE1C were co-expressed with olfactory-type G-proteins in the nose, suggesting that PDE1C dosage is increased in the stickleback olfactory transduction (OT pathway. In silico simulations of OT implied that the increased PDE1C dosage extends the longevity of the depolarization signals of the olfactory receptor neuron. Conclusion The predicted effect of the increase in PDE1C products on the OT pathway may play an important role in stickleback behavior and ecology. However, this possibility should be empirically examined. Our

Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

Science.gov (United States)

Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

2015-09-01

During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

Science.gov (United States)

Suneetha, A; Raja Rajeswari, K

2016-04-15

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via

Computational exploration of single-protein mechanics by steered molecular dynamics

Energy Technology Data Exchange (ETDEWEB)

Sotomayor, Marcos [Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio (United States)

2015-12-31

Hair cell mechanotransduction happens in tens of microseconds, involves forces of a few picoNewtons, and is mediated by nanometer-scale molecular conformational changes. As proteins involved in this process become identified and their high resolution structures become available, multiple tools are being used to explore their “single-molecule responses” to force. Optical tweezers and atomic force microscopy offer exquisite force and extension resolution, but cannot reach the high loading rates expected for high frequency auditory stimuli. Molecular dynamics (MD) simulations can reach these fast time scales, and also provide a unique view of the molecular events underlying protein mechanics, but its predictions must be experimentally verified. Thus a combination of simulations and experiments might be appropriate to study the molecular mechanics of hearing. Here I review the basics of MD simulations and the different methods used to apply force and study protein mechanics in silico. Simulations of tip link proteins are used to illustrate the advantages and limitations of this method.

Unstart Coupling Mechanism Analysis of Multiple-Modules Hypersonic Inlet

Directory of Open Access Journals (Sweden)

Jichao Hu

2013-01-01

Full Text Available The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Unstart coupling mechanism analysis of multiple-modules hypersonic inlet.

Science.gov (United States)

Hu, Jichao; Chang, Juntao; Wang, Lei; Cao, Shibin; Bao, Wen

2013-01-01

The combination of multiplemodules in parallel manner is an important way to achieve the much higher thrust of scramjet engine. For the multiple-modules scramjet engine, when inlet unstarted oscillatory flow appears in a single-module engine due to high backpressure, how to interact with each module by massflow spillage, and whether inlet unstart occurs in other modules are important issues. The unstarted flowfield and coupling characteristic for a three-module hypersonic inlet caused by center module II and side module III were, conducted respectively. The results indicate that the other two hypersonic inlets are forced into unstarted flow when unstarted phenomenon appears on a single-module hypersonic inlet due to high backpressure, and the reversed flow in the isolator dominates the formation, expansion, shrinkage, and disappearance of the vortexes, and thus, it is the major factor of unstart coupling of multiple-modules hypersonic inlet. The coupling effect among multiple modules makes hypersonic inlet be more likely unstarted.

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Science.gov (United States)

Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

2011-01-01

Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

Science.gov (United States)

Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

2017-01-01

Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

Multiple Wins, Multiple Organizations—How to Manage Institutional Interaction in Financing Forest Landscape Restoration (FLR

Directory of Open Access Journals (Sweden)

Astrid Carrapatoso

2018-03-01

Full Text Available By restoring forest ecosystems and fostering resilient and sustainable land use practices, Forest Landscape Restoration (FLR contributes to climate change mitigation, adaptation and sustainable development as well as the protection of biological diversity and combating desertification. This integrative approach provides the opportunity for multiple wins, but it necessitates the management of complex institutional interactions arising from the involvement of multiple international organizations. Focusing on the pivotal aspect of financing, this article surveys the landscape of public international institutions supporting FLR and analyzes the effectiveness of existing mechanisms of inter-institutional coordination and harmonization. Methodologically, our research is based on a document analysis, complemented by participant observation of the two Bonn Climate Change Conferences in May and November 2017 as well as the Global Landscapes Forum in December 2017. We find that financial institutions have established fairly effective rules for the management of positive and negative externalities through the introduction of co-benefits and safeguards. The fact that each institution has their own safeguards provisions, however, leads to significant transaction costs for recipient countries. In the discussion, we thus recommend that institutions should refrain from an unnecessary duplication of standards and focus on best practice.

Multiple Cranial Neuropathies Without Limb Involvements: Guillain-Barre Syndrome Variant?

OpenAIRE

Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-01-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunction...

Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

Energy Technology Data Exchange (ETDEWEB)

Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

2015-05-15

Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

International Nuclear Information System (INIS)

Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

2015-01-01

Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

Analysis of the outer membrane proteome and secretome of Bacteroides fragilis reveals a multiplicity of secretion mechanisms.

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Marlena M Wilson

Full Text Available Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes.

MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

DEFF Research Database (Denmark)

Leucci, E; Cocco, M; Onnis, A

2008-01-01

at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

Formation of (E)-nerolidol in tea (Camellia sinensis) leaves exposed to multiple stresses during tea manufacturing.

Science.gov (United States)

Zhou, Ying; Zeng, Lanting; Liu, Xiaoyu; Gui, Jiadong; Mei, Xin; Fu, Xiumin; Dong, Fang; Tang, Jingchi; Zhang, Lingyun; Yang, Ziyin

2017-09-15

(E)-Nerolidol is a volatile sesquiterpene that contributes to the floral aroma of teas (Camellia sinensis). The unique manufacturing process for oolong tea involves multiple stresses, resulting in a high content of (E)-nerolidol, which is not known to form in tea leaves. This study aimed to determine the formation mechanism of (E)-nerolidol in tea exposed to multiple stresses during tea manufacture. C. sinensis (E)-nerolidol synthase (CsNES) recombinant protein, found in the cytosol, was found to transform farnesyl diphosphate into (E)-nerolidol. CsNES was highly expressed during the oolong tea turn over process, resulting in (E)-nerolidol accumulation. Continuous mechanical damage, simulating the turn over process, significantly enhanced CsNES expression level and (E)-nerolidol content. The combination of low temperature stress and mechanical damage had a synergistic effect on (E)-nerolidol formation. This is the first evidence of (E)-nerolidol formation mechanism in tea leaves and a characteristic example of plant volatile formation in response to dual stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

A theory of economic growth with material/energy resources and dematerialization: interaction of three growth mechanisms

NARCIS (Netherlands)

Ayes, R.U.; van den Bergh, J.C.J.M.

2005-01-01

The nature of energy and material resources in a non-optimizing growth theory framework is clarified. This involves two modifications of the conventional theory. Firstly, multiple feedback mechanisms or "growth engines" are identified, such that the impact of the cost of production through demand on

Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

Science.gov (United States)

Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

2012-12-01

The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

Science.gov (United States)

Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

2017-07-01

Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

Effect of multiple repairs in girth welds of pipelines on the mechanical properties

International Nuclear Information System (INIS)

Vega, O.E.; Hallen, J.M.; Villagomez, A.; Contreras, A.

2008-01-01

This work presents the results of multiple weld repairs in the same area in seamless API X-52 microalloyed steel pipe. Four conditions of shielded metal arc welding repairs and one as-welded specimen of the girth weld were characterized to determine changes in the microstructure, grain size in the heat affected zone, and to evaluate their effect on the mechanical properties of the weld joints. The mechanical properties by means of tension tests, Charpy-V impact resistance and Vickers hardness of the welds were analyzed. The results indicate that significant changes are not generated in the microstructural constituents of the heat affected zone. Grain growth in the heat affected zone at the specimen mid-thickness with the number of repairs was observed. Tensile strength of the weld joints meets the requirement of the API 1104 standard even after the fourth weld repair. Significant reduction in Charpy-V impact resistance with the number of weld repairs was found when the notch location was in the intersection of the fusion line with the specimen mid-thickness. A significant increase in the Vickers hardness of the heat affected zone occurred after the first repair and a gradual decrease in the Vickers hardness occurred as the number of repairs increases

Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

Science.gov (United States)

Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

2014-01-01

This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

Cortical mechanisms for trans-saccadic memory and integration of multiple object features

Science.gov (United States)

Prime, Steven L.; Vesia, Michael; Crawford, J. Douglas

2011-01-01

Constructing an internal representation of the world from successive visual fixations, i.e. separated by saccadic eye movements, is known as trans-saccadic perception. Research on trans-saccadic perception (TSP) has been traditionally aimed at resolving the problems of memory capacity and visual integration across saccades. In this paper, we review this literature on TSP with a focus on research showing that egocentric measures of the saccadic eye movement can be used to integrate simple object features across saccades, and that the memory capacity for items retained across saccades, like visual working memory, is restricted to about three to four items. We also review recent transcranial magnetic stimulation experiments which suggest that the right parietal eye field and frontal eye fields play a key functional role in spatial updating of objects in TSP. We conclude by speculating on possible cortical mechanisms for governing egocentric spatial updating of multiple objects in TSP. PMID:21242142

Numerical calculations in elementary quantum mechanics using Feynman path integrals

International Nuclear Information System (INIS)

Scher, G.; Smith, M.; Baranger, M.

1980-01-01

We show that it is possible to do numerical calculations in elementary quantum mechanics using Feynman path integrals. Our method involves discretizing both time and space, and summing paths through matrix multiplication. We give numerical results for various one-dimensional potentials. The calculations of energy levels and wavefunctions take approximately 100 times longer than with standard methods, but there are other problems for which such an approach should be more efficient

The time-course of feature interference in agreement comprehension: Multiple mechanisms and asymmetrical attraction.

Science.gov (United States)

Tanner, Darren; Nicol, Janet; Brehm, Laurel

2014-10-01

Attraction interference in language comprehension and production may be as a result of common or different processes. In the present paper, we investigate attraction interference during language comprehension, focusing on the contexts in which interference arises and the time-course of these effects. Using evidence from event-related brain potentials (ERPs) and sentence judgment times, we show that agreement attraction in comprehension is best explained as morphosyntactic interference during memory retrieval. This stands in contrast to attraction as a message-level process involving the representation of the subject NP's number features, which is a strong contributor to attraction in production. We thus argue that the cognitive antecedents of agreement attraction in comprehension are non-identical with those of attraction in production, and moreover, that attraction in comprehension is primarily a consequence of similarity-based interference in cue-based memory retrieval processes. We suggest that mechanisms responsible for attraction during language comprehension are a subset of those involved in language production.

Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma

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Koulieris Efstathios

2012-04-01

Full Text Available Abstract Background HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig. Using this method, we measured intact immunoglobulin (heavy/light chain; HLC IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR in a series of IgG or IgA multiple myeloma (MM patients, to investigate and assess the contribution of these tests to disease evaluation. Patients and methods HevyLite™ assays were used in sera from 130 healthy individuals (HI and 103 MM patients, at time of diagnosis. In patients, the level of paraprotein was IgG in 78 (52 IgG-kappa, 26 IgG-lambda and IgΑ in 25 (13 IgΑ-kappa, 12 IgΑ-lambda. Durie-Salmon and International Staging System stages were evenly distributed. Symptomatic patients (n = 77 received treatment while asymptomatic ones (n = 26 were followed. Patients' median follow-up was at 32.6 months. HLCR was calculated with the involved Ig (either G or A as numerator. Results In HI, median IgG-kappa was 6.85, IgG-lambda 3.81, IgA-kappa 1.19 and IgA-lambda 0.98 g/L. The corresponding median involving HLC values in MM patients were 25.8, 23.45, 28.9 and 36.4 g/L. HLC-IgG related to anemia, high serum free light chain ratio and extensive bone marrow infiltration, while high HLCR correlated with the same plus increased β2-microglobulin. In addition, increased HLCR and the presence of immunoparesis correlated with time to treatment. Patients with high HLCR had a significantly shorter survival (p = 0.022; HLCR retained its prognostic value in multivariate analysis. Conclusions HLC and HLCR quantify the precise amount of the involved immunoglobulin more accurately than other methods; moreover, they carry prognostic information regarding survival in MM patients.

HLA-DP antigens are involved in the susceptibility to multiple sclerosis

DEFF Research Database (Denmark)

Ødum, Niels; Hyldig-Nielsen, J J; Morling, N

1988-01-01

Forty-five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA-DP using Primed Lymphocyte Typing. Thirty-nine MS-patients and 63 controls were also DNA-typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA-DP and -DR ge...... susceptibility to MS....

Language Learning Enhanced by Massive Multiple Online Role-Playing Games (MMORPGs) and the Underlying Behavioral and Neural Mechanisms

OpenAIRE

Zhang, Yongjun; Song, Hongwen; Liu, Xiaoming; Tang, Dinghong; Chen, Yue-e; Zhang, Xiaochu

2017-01-01

Massive Multiple Online Role-Playing Games (MMORPGs) have increased in popularity among children, juveniles, and adults since MMORPGs’ appearance in this digital age. MMORPGs can be applied to enhancing language learning, which is drawing researchers’ attention from different fields and many studies have validated MMORPGs’ positive effect on language learning. However, there are few studies on the underlying behavioral or neural mechanism of such effect. This paper reviews the educational app...

Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved.

Science.gov (United States)

Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M

2015-01-01

Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

Arbuscular mycorrhizal fungi for the biocontrol of plant-parasitic nematodes: a review of the mechanisms involved

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Nele eSchouteden

2015-11-01

Full Text Available Arbuscular mycorrhizal fungi (AMF are obligate root symbionts that can protect their host plant against biotic stress factors such as plant parasitic nematode (PPN infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead towards future field applications of AMF against PPN. The scientific community has entered an exciting era that provide the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead.

Arbuscular Mycorrhizal Fungi for the Biocontrol of Plant-Parasitic Nematodes: A Review of the Mechanisms Involved

Science.gov (United States)

Schouteden, Nele; De Waele, Dirk; Panis, Bart; Vos, Christine M.

2015-01-01

Arbuscular mycorrhizal fungi (AMF) are obligate root symbionts that can protect their host plant against biotic stress factors such as plant-parasitic nematode (PPN) infection. PPN consist of a wide range of species with different life styles that can cause major damage in many important crops worldwide. Various mechanisms have been proposed to play a role in the biocontrol effect of AMF against PPN. This review presents an overview of the different mechanisms that have been proposed, and discusses into more detail the plausibility of their involvement in the biocontrol against PPN specifically. The proposed mechanisms include enhanced plant tolerance, direct competition for nutrients and space, induced systemic resistance (ISR) and altered rhizosphere interactions. Recent studies have emphasized the importance of ISR in biocontrol and are increasingly placing rhizosphere effects on the foreground as well, both of which will be the focal point of this review. Though AMF are not yet widely used in conventional agriculture, recent data help to develop a better insight into the modes of action, which will eventually lead toward future field applications of AMF against PPN. The scientific community has entered an exciting era that provides the tools to actually unravel the underlying molecular mechanisms, making this a timely opportunity for a review of our current knowledge and the challenges ahead. PMID:26635750

Young, disadvantaged fathers' involvement with their infants: an ecological perspective.

Science.gov (United States)

Gavin, Loretta E; Black, Maureen M; Minor, Sherman; Abel, Yolanda; Papas, Mia A; Bentley, Margaret E

2002-09-01

To investigate fathers' involvement with their children using an ecological model, multiple respondents, and a comprehensive definition of fathers' involvement. The study's primary objectives were: (a) to describe the characteristics of fathers whose infants are born to low-income, urban, African-American adolescent mothers; (b) to describe the ways in which fathers are involved with their children; and (c) to identify factors associated with fathers' involvement. A total of 181 first-time mothers (aged parenting. Mothers provided the name of their infant's father; 109 (60%) of the fathers also agreed to participate. Baseline interviews of mothers, fathers, and grandmothers addressed demographic characteristics, relationships, and the father's involvement with his child. Three multivariate regression models were used to identify factors associated with paternal involvement, explaining 35% to 51% of the variability in father involvement. Regardless of the respondent (mother, father, or grandmother), paternal involvement was predicted most strongly by the quality of the parents' romantic relationship. The father's employment status, the maternal grandmother's education, and the father's relationship with the baby's maternal grandmother were also associated with paternal involvement. The study confirmed the value of an ecological perspective that uses multiple informants and a comprehensive definition of father involvement that includes multiple role functions. Efforts to increase paternal involvement should help young parents separate the father's relationship with their child from the romantic relationship between the mother and father, address the roles played by maternal grandmothers, and assist fathers to complete their education, and obtain and keep jobs.

MULTIPLE OBJECTS

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A. A. Bosov

2015-04-01

Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

The immunogenetics of multiple sclerosis

DEFF Research Database (Denmark)

Svejgaard, A.

2008-01-01

with complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...

Multiple sporadic colorectal cancers display a unique methylation phenotype.

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Victoria Gonzalo

Full Text Available Epigenetics are thought to play a major role in the carcinogenesis of multiple sporadic colorectal cancers (CRC. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the epigenetic signature of multiple CRC using a genome-scale DNA methylation profiling. We analyzed 12 patients with synchronous CRC and 29 age-, sex-, and tumor location-paired patients with solitary tumors from the EPICOLON II cohort. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significant results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP; KRAS and BRAF mutations and mismatch repair deficiency status. Functional annotation clustering was performed. We identified 102 CpG sites that showed significant DNA hypermethylation in multiple tumors with respect to the solitary counterparts (difference in β value ≥0.1. Methylight assays validated the results for 4 selected genes (p = 0.0002. Eight out of 12(66.6% multiple tumors were classified as CIMP-high, as compared to 5 out of 29(17.2% solitary tumors (p = 0.004. Interestingly, 76 out of the 102 (74.5% hypermethylated CpG sites found in multiple tumors were also seen in CIMP-high tumors. Functional analysis of hypermethylated genes found in multiple tumors showed enrichment of genes involved in different tumorigenic functions. In conclusion, multiple CRC are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity.

Longer epilepsy duration and multiple lobe involvement predict worse seizure outcomes for patients with refractory temporal lobe epilepsy associated with neurocysticercosis

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Lucas Crociati Meguins

2015-12-01

Full Text Available ABSTRACT Objective To investigate the surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS and neurocysticercosis (NCC. Methods A retrospective investigation of patients with TLE-HS was conducted in a tertiary center. Results Seventy-nine (62.2%, 37 (29.1%, 6 (4.7%, and 5 (3.9% patients were Engel class I, II, III, and IV, respectively. Fifty-two (71.2% patients with epilepsy durations ≤ 10 years prior to surgery were seizure-free 1 year after the operation compared to 27 (50.0% patients with epilepsy durations > 10 years (p = 0.0121. Forty-three (72.9% patients with three or fewer lobes affected by NCC were seizure-free one year after the operation, and 36 (52.9% patients with more than three involved lobes were seizure-free after surgery (p = 0.0163. Conclusions Longer epilepsy durations and multiple lobe involvement predicted worse seizure outcomes in TLE-HS plus NCC patients.

The Vulnerability of Vessels Involved in the Role of Embolism and Hypoperfusion in the Mechanisms of Ischemic Cerebrovascular Diseases

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Yong Peng Yu

2016-01-01

Full Text Available Accurate definition and better understanding of the mechanisms of stroke are crucial as this will guide the effective care and therapy. In this paper, we review the previous basic and clinical researches on the causes or mechanisms of ischemic cerebrovascular diseases (ICVD and interpret the correlation between embolism and hypoperfusion based on vascular stenosis and arterial intimal lesions. It was suggested that if there is no embolus (dynamic or in situ emboli, there might be no cerebral infarction. Three kinds of different clinical outcomes of TIA were theoretically interpreted based on its mechanisms. We suppose that there is a correlation between embolism and hypoperfusion, and which mechanisms (hypoperfusion or hypoperfusion induced microemboli playing the dominant role in each type of ICVD depends on the unique background of arterial intimal lesions (the vulnerability of vessels. That is to say, the vulnerability of vessels is involved in the role of embolism and hypoperfusion in the mechanisms of ischemic cerebrovascular diseases. This inference might enrich and provide better understandings for the underlying etiologies of ischemic cerebrovascular events.

Confocal Cornea Microscopy Detects Involvement of Corneal Nerve Fibers in a Patient with Light-Chain Amyloid Neuropathy Caused by Multiple Myeloma: A Case Report

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Dietrich Sturm

2016-06-01

Full Text Available Changes in the subbasal corneal plexus detected by confocal cornea microscopy (CCM have been described for various types of neuropathy. An involvement of these nerves within light-chain (AL amyloid neuropathy (a rare cause of polyneuropathy has never been shown. Here, we report on a case of a patient suffering from neuropathy caused by AL amyloidosis and underlying multiple myeloma. Small-fiber damage was detected by CCM.

The adaptor molecule signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is essential in mechanisms involving the Fyn tyrosine kinase for induction and progression of collagen-induced arthritis.

Science.gov (United States)

Zhong, Ming-Chao; Veillette, André

2013-11-01

Signaling lymphocytic activation molecule-associated protein (SAP) is an Src homology 2 domain-only adaptor involved in multiple immune cell functions. It has also been linked to immunodeficiencies and autoimmune diseases, such as systemic lupus erythematosus. Here, we examined the role and mechanism of action of SAP in autoimmunity using a mouse model of autoimmune arthritis, collagen-induced arthritis (CIA). We found that SAP was essential for development of CIA in response to collagen immunization. It was also required for production of collagen-specific antibodies, which play a key role in disease pathogenesis. These effects required SAP expression in T cells, not in B cells. In mice immunized with a high dose of collagen, the activity of SAP was nearly independent of its ability to bind the protein tyrosine kinase Fyn and correlated with the capacity of SAP to promote full differentiation of follicular T helper (TFH) cells. However, with a lower dose of collagen, the role of SAP was more dependent on Fyn binding, suggesting that additional mechanisms other than TFH cell differentiation were involved. Further studies suggested that this might be due to a role of the SAP-Fyn interaction in natural killer T cell development through the ability of SAP-Fyn to promote Vav-1 activation. We also found that removal of SAP expression during progression of CIA attenuated disease severity. However, it had no effect on disease when CIA was clinically established. Together, these results indicate that SAP plays an essential role in CIA because of Fyn-independent and Fyn-dependent effects on TFH cells and, possibly, other T cell types.

Multiple-membrane multiple-electrolyte redox flow battery design

Science.gov (United States)

Yan, Yushan; Gu, Shuang; Gong, Ke

2017-05-02

A redox flow battery is provided. The redox flow battery involves multiple-membrane (at least one cation exchange membrane and at least one anion exchange membrane), multiple-electrolyte (one electrolyte in contact with the negative electrode, one electrolyte in contact with the positive electrode, and at least one electrolyte disposed between the two membranes) as the basic characteristic, such as a double-membrane, triple electrolyte (DMTE) configuration or a triple-membrane, quadruple electrolyte (TMQE) configuration. The cation exchange membrane is used to separate the negative or positive electrolyte and the middle electrolyte, and the anion exchange membrane is used to separate the middle electrolyte and the positive or negative electrolyte.

Perception of the Body in Space: Mechanisms

Science.gov (United States)

Young, Laurence R.

1991-01-01

The principal topic is the perception of body orientation and motion in space and the extent to which these perceptual abstraction can be related directly to the knowledge of sensory mechanisms, particularly for the vestibular apparatus. Spatial orientation is firmly based on the underlying sensory mechanisms and their central integration. For some of the simplest situations, like rotation about a vertical axis in darkness, the dynamic response of the semicircular canals furnishes almost enough information to explain the sensations of turning and stopping. For more complex conditions involving multiple sensory systems and possible conflicts among their messages, a mechanistic response requires significant speculative assumptions. The models that exist for multisensory spatial orientation are still largely of the non-rational parameter variety. They are capable of predicting relationships among input motions and output perceptions of motion, but they involve computational functions that do not now and perhaps never will have their counterpart in central nervous system machinery. The challenge continues to be in the iterative process of testing models by experiment, correcting them where necessary, and testing them again.

Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

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Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

2009-12-01

Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

Mechanisms of Candida biofilm drug resistance

Science.gov (United States)

Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

2013-01-01

Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

Chemotherapeutics-resistance "arms" race: An update on mechanisms involved in resistance limiting EGFR inhibitors in lung cancer.

Science.gov (United States)

Singh, Pankaj Kumar; Silakari, Om

2017-10-01

Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc., in the development of tolerance towards the EGFR TKI's, along with other commonly known mechanisms, such as amplification of signalling pathways such as, c-MET, Erbb2, AXL, additional acquired secondary mutations (PIK3CA, BRAF), or phenotypic transformation (small cell or epithelial to mesenchymal transitions). Interestingly, a recent study showed development of resistance via another point mutation, C797S, in case of tumors which were previously resistant and were administered agents capable of overcoming T790M gatekeeper mutation based resistance. Thus, raising serious concern over the direction of drug development involving tyrosine kinases such as EGFR. Current approaches focussing on development of third generation inhibitors, dual inhibitors or inhibitors of HSP90 have shown significant activity but do not answer the long term question of resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

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Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

2011-01-01

The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

Involvement of protein kinase C in the mechanism of action of Escherichia coli heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205

International Nuclear Information System (INIS)

Gupta, Dyuti Datta; Saha, Subhrajit; Chakrabarti, Manoj K.

2005-01-01

The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP 3 -mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKCα) was specified using isotype-specific pseudosubstrate, which showed pronounce enzyme activity. Inhibition of enzyme activity by PKCα-specific inhibitor Goe6976 and immunoblott study employing isotype-specific antibody further demonstrated the involvement of calcium-dependent isoform of PKC in the mechanism of action of E. coli STa. Moreover, inhibition of guanylate cyclase activity by PKCα-specific inhibitor Goe6976 suggested the involvement of PKCα in the regulation of guanylate cyclase activity

Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

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A. Achiron

2004-01-01

Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

Geophysical Factor Resolving of Rainfall Mechanism for Super Typhoons by Using Multiple Spatiotemporal Components Analysis

Science.gov (United States)

Huang, Chien-Lin; Hsu, Nien-Sheng

2016-04-01

This study develops a novel methodology to resolve the geophysical cause of typhoon-induced rainfall considering diverse dynamic co-evolution at multiple spatiotemporal components. The multi-order hidden patterns of complex hydrological process in chaos are detected to understand the fundamental laws of rainfall mechanism. The discovered spatiotemporal features are utilized to develop a state-of-the-art descriptive statistical model for mechanism validation, modeling and further prediction during typhoons. The time series of hourly typhoon precipitation from different types of moving track, atmospheric field and landforms are respectively precede the signal analytical process to qualify each type of rainfall cause and to quantify the corresponding affected degree based on the measured geophysical atmospheric-hydrological variables. This study applies the developed methodology in Taiwan Island which is constituted by complex diverse landform formation. The identified driving-causes include: (1) cloud height to ground surface; (2) co-movement effect induced by typhoon wind field with monsoon; (3) stem capacity; (4) interaction between typhoon rain band and terrain; (5) structural intensity variance of typhoon; and (6) integrated cloudy density of rain band. Results show that: (1) for the central maximum wind speed exceeding 51 m/sec, Causes (1) and (3) are the primary ones to generate rainfall; (2) for the typhoon moving toward the direction of 155° to 175°, Cause (2) is the primary one; (3) for the direction of 90° to 155°, Cause (4) is the primary one; (4) for the typhoon passing through mountain chain which above 3500 m, Cause (5) is the primary one; and (5) for the moving speed lower than 18 km/hr, Cause (6) is the primary one. Besides, the multiple geophysical component-based precipitation modeling can achieve 81% of average accuracy and 0.732 of average correlation coefficient (CC) within average 46 hours of duration, that improve their predictability.

Effective Information Technology Governance Mechanisms: An Australian Study

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Syaiful Ali

2006-01-01

Full Text Available Growing importance of information technology (IT, as a strategic factor for organizations in achieving their objectives, have raised the concern of organizations in establishing and implementing effective IT governance. This study seeks to empirically examine the individual IT governance mechanisms that influence the overall effectiveness of IT governance. The data were obtained by using web based survey from 176 members of ISACA (Information Systems and Audit Control Association Australia. This study examines the influences of six proposed IT governance mechanisms on the overall effectiveness of IT governance. Using Factor Analysis and Multiple Regression techniques, the current study finds significant positive relationships between the overall level of effective IT governance and the following four IT governance mechanisms: the existence of ethics/ culture of compliance in IT, corporate communication systems, an IT strategy committee, and the involvement of senior management in IT.

Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

Science.gov (United States)

Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

1984-05-01

Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

Current perspectives on the mechanism of action of artemisinins.

Science.gov (United States)

Golenser, Jacob; Waknine, Judith H; Krugliak, Miriam; Hunt, Nicholas H; Grau, Georges E

2006-12-01

Artemisinin derivatives are the most recent single drugs approved and introduced for public antimalarial treatment. Although their recommended use is for treatment of Plasmodium falciparum infection, these drugs also act against other parasites, as well as against tumor cells. The mechanisms of action attributed to artemisinin include interference with parasite transport proteins, disruption of parasite mitochondrial function, modulation of host immune function and inhibition of angiogenesis. Artemisinin combination therapies are currently the preferred treatment for malaria. These combinations may prevent the induction of parasite drug resistance. However, in view of the multiple mechanisms involved, especially when additional drugs are used, the combined therapy should be carefully examined for antagonistic effects. It is now a general theory that the crucial mechanism is interference with plasmodial SERCA. Therefore, future development of resistance may be associated with overproduction or mutations of this transporter. However, a general mechanism, such as alterations in general drug transport pathways, is feasible. In this article, we review the evidence for each mechanism of action suggested.

A Mechanism for Land-Atmosphere Feedback Involving Planetary Wave Structures

Science.gov (United States)

Koster, Randal D.; Chang, Yehui; Schubert, Siegfried D.

2014-01-01

While the ability of land surface conditions to influence the atmosphere has been demonstrated in various modeling and observational studies, the precise mechanisms by which land-atmosphere feedback occurs are still largely unknown particularly the mechanisms that allow land moisture state in one region to affect atmospheric conditions in another. Such remote impacts are examined here in the context of atmospheric general circulation model (AGCM) simulations, leading to the identification of one potential mechanism: the phase-locking and amplification of a planetary wave through the imposition of a spatial pattern of soil moisture at the land surface. This mechanism, shown here to be relevant in the AGCM, apparently also operates in nature, as suggested by supporting evidence found in reanalysis data.

Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

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Williams Mandy

2005-01-01

Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

Mechanisms for cytoplasmic organization: an overview.

Science.gov (United States)

Pagliaro, L

2000-01-01

One of the basic characteristics of life is the intrinsic organization of cytoplasm, yet we know surprisingly little about the manner in which cytoplasmic macromolecules are arranged. It is clear that cytoplasm is not the homogeneous "soup" it was once envisioned to be, but a comprehensive model for cytoplasmic organization is not available in modern cell biology. The premise of this volume is that phase separation in cytoplasm may play a role in organization at the subcellular level. Other mechanisms for non-membrane-bounded intracellular organization have previously been proposed. Some of these will be reviewed in this chapter. Multiple mechanisms, involving phase separation, specific intracellular targeting, formation of macromolecular complexes, and channeling, all could well contribute to cytoplasmic organization. Temporal and spatial organization, as well as composition, are likely to be important in defining the characteristics of cytoplasm.

Mechanisms Involved in Nematode Control by Endophytic Fungi

NARCIS (Netherlands)

Schouten, Sander

2016-01-01

Colonization of plants by particular endophytic fungi can provide plants with improved defenses toward nematodes. Evidently, such endophytes can be important in developing more sustainable agricultural practices. The mechanisms playing a role in this quantitative antagonism are poorly understood

A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

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Xinkui Liu

2018-01-01

Full Text Available Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

Design of clinical trials involving multiple hypothesis tests with a common control.

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Schou, I Manjula; Marschner, Ian C

2017-07-01

Randomized clinical trials comparing several treatments to a common control are often reported in the medical literature. For example, multiple experimental treatments may be compared with placebo, or in combination therapy trials, a combination therapy may be compared with each of its constituent monotherapies. Such trials are typically designed using a balanced approach in which equal numbers of individuals are randomized to each arm, however, this can result in an inefficient use of resources. We provide a unified framework and new theoretical results for optimal design of such single-control multiple-comparator studies. We consider variance optimal designs based on D-, A-, and E-optimality criteria, using a general model that allows for heteroscedasticity and a range of effect measures that include both continuous and binary outcomes. We demonstrate the sensitivity of these designs to the type of optimality criterion by showing that the optimal allocation ratios are systematically ordered according to the optimality criterion. Given this sensitivity to the optimality criterion, we argue that power optimality is a more suitable approach when designing clinical trials where testing is the objective. Weighted variance optimal designs are also discussed, which, like power optimal designs, allow the treatment difference to play a major role in determining allocation ratios. We illustrate our methods using two real clinical trial examples taken from the medical literature. Some recommendations on the use of optimal designs in single-control multiple-comparator trials are also provided. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sentencing Multiple Crimes

DEFF Research Database (Denmark)

Most people assume that criminal offenders have only been convicted of a single crime. However, in reality almost half of offenders stand to be sentenced for more than one crime.The high proportion of multiple crime offenders poses a number of practical and theoretical challenges for the criminal......, and psychology offer their perspectives to the volume. A comprehensive examination of the dynamics involved with sentencing multiple offenders has the potential to be a powerful tool for legal scholars and professionals, particularly given the practical importance of the topic and the relative dearth of research...

The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

Science.gov (United States)

Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

2010-05-01

The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms

The Toxicity of Nanoparticles Depends on Multiple Molecular and Physicochemical Mechanisms

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Yue-Wern Huang

2017-12-01

Full Text Available Nanotechnology is an emerging discipline that studies matters at the nanoscale level. Eventually, the goal is to manipulate matters at the atomic level to serve mankind. One growing area in nanotechnology is biomedical applications, which involve disease management and the discovery of basic biological principles. In this review, we discuss characteristics of nanomaterials, with an emphasis on transition metal oxide nanoparticles that influence cytotoxicity. Identification of those properties may lead to the design of more efficient and safer nanosized products for various industrial purposes and provide guidance for assessment of human and environmental health risk. We then investigate biochemical and molecular mechanisms of cytotoxicity that include oxidative stress-induced cellular events and alteration of the pathways pertaining to intracellular calcium homeostasis. All the stresses lead to cell injuries and death. Furthermore, as exposure to nanoparticles results in deregulation of the cell cycle (i.e., interfering with cell proliferation, the change in cell number is a function of cell killing and the suppression of cell proliferation. Collectively, the review article provides insights into the complexity of nanotoxicology.

Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

Energy Technology Data Exchange (ETDEWEB)

Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

2012-06-15

Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

Current knowledge of detoxification mechanisms of xenobiotic in honey bees.

Science.gov (United States)

Gong, Youhui; Diao, Qingyun

2017-01-01

The western honey bee Apis mellifera is the most important managed pollinator species in the world. Multiple factors have been implicated as potential causes or factors contributing to colony collapse disorder, including honey bee pathogens and nutritional deficiencies as well as exposure to pesticides. Honey bees' genome is characterized by a paucity of genes associated with detoxification, which makes them vulnerable to specific pesticides, especially to combinations of pesticides in real field environments. Many studies have investigated the mechanisms involved in detoxification of xenobiotics/pesticides in honey bees, from primal enzyme assays or toxicity bioassays to characterization of transcript gene expression and protein expression in response to xenobiotics/insecticides by using a global transcriptomic or proteomic approach, and even to functional characterizations. The global transcriptomic and proteomic approach allowed us to learn that detoxification mechanisms in honey bees involve multiple genes and pathways along with changes in energy metabolism and cellular stress response. P450 genes, is highly implicated in the direct detoxification of xenobiotics/insecticides in honey bees and their expression can be regulated by honey/pollen constitutes, resulting in the tolerance of honey bees to other xenobiotics or insecticides. P450s is also a key detoxification enzyme that mediate synergism interaction between acaricides/insecticides and fungicides through inhibition P450 activity by fungicides or competition for detoxification enzymes between acaricides. With the wide use of insecticides in agriculture, understanding the detoxification mechanism of insecticides in honey bees and how honeybees fight with the xenobiotis or insecticides to survive in the changing environment will finally benefit honeybees' management.

Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

Science.gov (United States)

Ding, Jiang-Hua; Chang, Yu-Sui

2012-08-01

Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats

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Katagiri Ayano

2012-03-01

Full Text Available Abstract Background It has been reported that the P2Y12 receptor (P2Y12R is involved in satellite glial cells (SGCs activation, indicating that P2Y12R expressed in SGCs may play functional roles in orofacial neuropathic pain mechanisms. However, the involvement of P2Y12R in orofacial neuropathic pain mechanisms is still unknown. We therefore studied the reflex to noxious mechanical or heat stimulation of the tongue, P2Y12R and glial fibrillary acidic protein (GFAP immunohistochemistries in the trigeminal ganglion (TG in a rat model of unilateral lingual nerve crush (LNC to evaluate role of P2Y12R in SGC in lingual neuropathic pain. Results The head-withdrawal reflex thresholds to mechanical and heat stimulation of the lateral tongue were significantly decreased in LNC-rats compared to sham-rats. These nocifensive effects were apparent on day 1 after LNC and lasted for 17 days. On days 3, 9, 15 and 21 after LNC, the mean relative number of TG neurons encircled with GFAP-immunoreactive (IR cells significantly increased in the ophthalmic, maxillary and mandibular branch regions of TG. On day 3 after LNC, P2Y12R expression occurred in GFAP-IR cells but not neuronal nuclei (NeuN-IR cells (i.e. neurons in TG. After 3 days of successive administration of the P2Y12R antagonist MRS2395 into TG in LNC-rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly decreased coincident with a significant reversal of the lowered head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue compared to vehicle-injected rats. Furthermore, after 3 days of successive administration of the P2YR agonist 2-MeSADP into the TG in naïve rats, the mean relative number of TG neurons encircled with GFAP-IR cells was significantly increased and head-withdrawal reflex thresholds to mechanical and heat stimulation of the tongue were significantly decreased in a dose-dependent manner compared to vehicle-injected rats

Safe Dynamic Multiple Inheritance

DEFF Research Database (Denmark)

Ernst, Erik

2002-01-01

Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

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Karunaratne SHP Parakrama

2008-08-01

Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

Adolescents' Perceptions of Their Fathers' Involvement: Significance to School Attitudes.

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Flouri, Eirini; Buchanan, Ann; Bream, Victoria

2002-01-01

Based on data from 2,722 British adolescents, this study explores whether perceived father involvement can be associated with school attitudes. Multiple regression analysis showed that both father involvement and mother involvement contributed significantly and independently to positive school attitudes. Furthermore, the association between father…

Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

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Farrero, Eva; Prats, Enric; Povedano, Mónica; Martinez-Matos, J Antonio; Manresa, Frederic; Escarrabill, Joan

2005-06-01

To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). Retrospective study in a tertiary care referral center. HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

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Lewei Duan

2013-01-01

Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

[A case of transverse colon cancer with multiple liver metastases and hepatic pedicle lymph node involvement showing pathological complete response by XELOX plus bevacizumab].

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Mukai, Toshiki; Akiyoshi, Takashi; Koga, Rintaro; Arita, Junichi; Saiura, Akio; Ikeda, Atsushi; Nagasue, Yasutomo; Oikawa, Yoshinori; Yamakawa, Keiko; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi; Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Yamamoto, Chiriko; Yamaguchi, Toshiharu

2012-12-01

A 70-year-old woman was referred to our hospital because of abdominal pain. Abdominal computed tomography(CT)and colonoscopy revealed transverse colon cancer with multiple liver metastases, with involvement of the hepatic pedicle and superior mesenteric artery lymph nodes. The patient received eight courses of XELOX plus bevacizumab, and CT showed a decrease in the size of the liver metastases and hepatic pedicle lymphadenopathy. Right hemicolectomy, partial hepatectomy, and hepatic pedicle lymph node resection were performed. Histopathological examination of the resected tissue revealed no residual cancer cells, suggesting a pathological complete response. The patient remains well 7 months after operation, without any signs of recurrence. Surgical resection should be considered for patients with initially unresectable colon cancer with liver metastases and hepatic pedicle lymph nodes involvement if systemic chemotherapy is effective.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

OpenAIRE

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...

Mechanisms involved in the psychological distress of Black Caribbeans in the United States

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Govia, Ishtar O.

The mental health of ethnic minorities in the United States is of urgent concern. The accelerated growth of groups of ethnic minorities and immigrants in the United States and the stressors to which they are exposed, implores academic researchers to investigate more deeply health disparities and the factors that exacerbate or minimize such inequalities. This dissertation attended to that concern. It used data from the National Survey of American Life (NSAL), the first survey with a national representative sample of Black Caribbeans, to explore mechanisms that involved in the psychological distress of Black Caribbeans in the United States. In a series of three studies, the dissertation investigated the role and consequence of (1) chronic discrimination, immigration factors, and closeness to ethnic and racial groups; (2) personal control and social support; and (3) family relations and social roles in the psychological distress of Black Caribbeans. Study 1 examined how the associations between discrimination and psychological distress were buffered or exacerbated by closeness to ethnic group and closeness to racial group. It also examined how these associations differed depending on immigration factors. Results indicated that the buffering or exacerbating effect of ethnic and racial group closeness varied according to the type of discrimination (subtle or severe) and were more pronounced among those born in the United States. Using the stress process framework, Study 2 tested moderation and mediation models of the effects of social support and personal control in the association between discrimination and distress. Results from a series of analyses on 579 respondents suggested that personal control served as a mediator in this relationship and that emotional support exerted a direct distress deterring function. Study 3 investigated sex differences in the associations between social roles, intergenerational family relationship perceptions and distress. Results

Advanced paternal age effects in neurodevelopmental disorders-review of potential underlying mechanisms.

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Janecka, M; Mill, J; Basson, M A; Goriely, A; Spiers, H; Reichenberg, A; Schalkwyk, L; Fernandes, C

2017-01-31

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders.

Study of the Genes and Mechanism Involved in the Radioadaptive Response

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Dasgupta, Pushan R.

2009-01-01

The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

MULTIPLE SPINAL CANAL MENINGIOMAS

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Nandigama Pratap Kumar

2016-10-01

Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

Dual Headquarters Involvement in Multibusiness Firms

DEFF Research Database (Denmark)

Nell, Phillip Christopher; Kappen, Philip; Dellestrand, Henrik

The strategy literature has shown that headquarters involve themselves into subsidiary operations to add value. Yet, little is known about the extent to which multiple headquarters do so. Therefore, we investigate antecedents of corporate and divisional headquarters’ involvement in innovation...... development projects of subsidiaries. Analyses of 85 innovation development projects reveal that dual innovation importance (innovation that is important for the division and the rest of the firm), and dual dual embeddedness (innovating subsidiary is embedded both within the division and in the rest...... of the firm) lead to greater dual headquarters involvement, especially when the innovation development network is large. The results contribute to the literature on complex parenting and theory of selective headquarters involvement....

Higgsplosion: Solving the hierarchy problem via rapid decays of heavy states into multiple Higgs bosons

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Khoze, Valentin V.; Spannowsky, Michael

2018-01-01

We introduce and discuss two inter-related mechanisms operative in the electroweak sector of the Standard Model at high energies. Higgsplosion, the first mechanism, occurs at some critical energy in the 25 to 103 TeV range, and leads to an exponentially growing decay rate of highly energetic particles into multiple Higgs bosons. We argue that this is a well-controlled non-perturbative phenomenon in the Higgs-sector which involves the final state Higgs multiplicities n in the regime nλ ≫ 1 where λ is the Higgs self-coupling. If this mechanism is realised in nature, the cross-sections for producing ultra-high multiplicities of Higgs bosons are likely to become observable and even dominant in this energy range. At the same time, however, the apparent exponential growth of these cross-sections at even higher energies will be tamed and automatically cut-off by a related Higgspersion mechanism. As a result, and in contrast to previous studies, multi-Higgs production does not violate perturbative unitarity. Building on this approach, we then argue that the effects of Higgsplosion alter quantum corrections from very heavy states to the Higgs boson mass. Above a certain energy, which is much smaller than their masses, these states would rapidly decay into multiple Higgs bosons. The heavy states become unrealised as they decay much faster than they are formed. The loop integrals contributing to the Higgs mass will be cut off not by the masses of the heavy states, but by the characteristic loop momenta where their decay widths become comparable to their masses. Hence, the cut-off scale would be many orders of magnitude lower than the heavy mass scales themselves, thus suppressing their quantum corrections to the Higgs boson mass.

Emerging drugs for primary progressive multiple sclerosis.

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Narayan, Ram Narendra; Forsthuber, Thomas; Stüve, Olaf

2018-04-24

The identification of effective therapies for progressive forms of multiple sclerosis (MS) has remains a priority and challenge for the global MS community. Despite a few proposed mechanisms, a more complete understanding of the mechanisms involved in the pathogenesis of these MS phenotypes, animal models that incorporate these pathogenic characteristics, novel trial designs, drug repurposing strategies, and new models of collaboration between clinical and basic science personnel may be required in identifying effective therapies. Areas covered: Here, we review the current knowledge on putative pathogenic mechanisms in primary progressive MS (PPMS). Also, the rationale and outcomes of key phase II or III trial initiatives in PPMS are summarized. Future perspectives are outlined. Expert opinion: The recent approval of ocrelizumab is a major milestone forward in the therapy of PPMS. One reason for success of this drug is appropriate patient selection. The ultimate goal in PPMS therapy should be the reversal of disability, and the arrest of disease progression. Our current understanding of PPMS suggests that a combination of immune-modulatory, myelin-restorative, and neuro-regenerative therapies particularly early in the disease course would be a reasonable strategy. Finally, selection of appropriate patients, selection of appropriate outcomes and monitoring therapy is again crucial for success of therapeutic strategies.

Neuromodulatory treatments for chronic pain: efficacy and mechanisms

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Jensen, Mark P.; Day, Melissa A.; Miró, Jordi

2017-01-01

Chronic pain is common, and the available treatments do not provide adequate relief for most patients. Neuromodulatory interventions that modify brain processes underlying the experience of pain have the potential to provide substantial relief for some of these patients. The purpose of this Review is to summarize the state of knowledge regarding the efficacy and mechanisms of noninvasive neuromodulatory treatments for chronic pain. The findings provide support for the efficacy and positive side-effect profile of hypnosis, and limited evidence for the potential efficacy of meditation training, noninvasive electrical stimulation procedures, and neurofeedback procedures. Mechanisms research indicates that hypnosis influences multiple neurophysiological processes involved in the experience of pain. Evidence also indicates that mindfulness meditation has both immediate and long-term effects on cortical structures and activity involved in attention, emotional responding and pain. Less is known about the mechanisms of other neuromodulatory treatments. On the basis of the data discussed in this Review, training in the use of self-hypnosis might be considered a viable ‘first-line’ approach to treat chronic pain. More-definitive research regarding the benefits and costs of meditation training, noninvasive brain stimulation and neurofeedback is needed before these treatments can be recommended for the treatment of chronic pain. PMID:24535464

Extracting the Beat: An Experience-dependent Complex Integration of Multisensory Information Involving Multiple Levels of the Nervous System

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Laurel J. Trainor

2009-04-01

Full Text Available In a series of studies we have shown that movement (or vestibular stimulation that is synchronized to every second or every third beat of a metrically ambiguous rhythm pattern biases people to perceive the meter as a march or as a waltz, respectively. Riggle (this volume claims that we postulate an "innate", "specialized brain unit" for beat perception that is "directly" influenced by vestibular input. In fact, to the contrary, we argue that experience likely plays a large role in the development of rhythmic auditory-movement interactions, and that rhythmic processing in the brain is widely distributed and includes subcortical and cortical areas involved in sound processing and movement. Further, we argue that vestibular and auditory information are integrated at various subcortical and cortical levels along with input from other sensory modalities, and it is not clear which levels are most important for rhythm processing or, indeed, what a "direct" influence of vestibular input would mean. Finally, we argue that vestibular input to sound location mechanisms may be involved, but likely cannot explain the influence of vestibular input on the perception of auditory rhythm. This remains an empirical question for future research.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

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Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Multiple mutualist effects on genomewide expression in the tripartite association between Medicago truncatula, nitrogen-fixing bacteria and mycorrhizal fungi.

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Afkhami, Michelle E; Stinchcombe, John R

2016-10-01

While all species interact with multiple mutualists, the fitness consequences and molecular mechanisms underlying these interactions remain largely unknown. We combined factorial ecological experiments with genomewide expression analyses to examine the phenotypic and transcriptomic responses of model legume Medicago truncatula to rhizobia and mycorrhizal fungi. We found synergistic effects of these mutualists on plant performance and examined unique features of plant gene expression responses to multiple mutualists. There were genomewide signatures of mutualists and multiple mutualists on expression, with partners often affecting unique sets of genes. Mycorrhizal fungi had stronger effects on plant expression than rhizobia, with 70% of differentially expressed genes affected by fungi. Fungal and bacterial mutualists had joint effects on 10% of differentially expressed genes, including unexpected, nonadditive effects on some genes with important functions such as nutrient metabolism. For a subset of genes, interacting with multiple mutualists even led to reversals in the direction of expression (shifts from up to downregulation) compared to interacting with single mutualists. Rhizobia also affected the expression of several mycorrhizal genes, including those involved in nutrient transfer to host plants, indicating that partner species can also impact each other's molecular phenotypes. Collectively, these data illustrate the diverse molecular mechanisms and transcriptional responses associated with the synergistic benefits of multiple mutualists. © 2016 John Wiley & Sons Ltd.

Rehabilitation and multiple sclerosis

DEFF Research Database (Denmark)

Dalgas, Ulrik

2011-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

Comparisons of auction mechanisms in a multiple unit setting: A consideration for restructuring electric power markets

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Bernard, John Charles

The objective of this study was to compare the performance of five single sided auctions that could be used in restructured electric power markets across different market sizes in a multiple unit setting. Auction selection would profoundly influence an industry over $200 billion in size in the United States, and the consequences of implementing an inappropriate mechanism would be great. Experimental methods were selected to analyze the auctions. Two rounds of experiments were conducted, the first testing the sealed offer last accepted offer (LAO) and first rejected offer (FRO), and the clock English (ENG) and sealed offer English (SOE) in markets of sizes two and six. The FRO, SOE, and ENG used the same pricing rule. Second round testing was on the LAO, FRO, and the nonuniform price multiple unit Vickrey (MUV) in markets of sizes two, four, and six. Experiments lasted 23 and 75 periods for rounds 1 and 2 respectively. Analysis of variance and contrast analysis were used to examine the data. The four performance measures used were price, efficiency, profits per unit, and supply revelation. Five basic principles were also assessed: no sales at losses, all low cost capacity should be offered and sold, no high cost capacity should sell, and the market should clear. It was expected group size and auction type would affect performance. For all performance measures, group size was a significant variable, with smaller groups showing poorer performance. Auction type was significant only for the efficiency performance measure, where clock auctions outperformed the others. Clock auctions also proved superior for the first four principles. The FRO performed poorly in almost all situations, and should not be a preferred mechanism in any market. The ENG was highly efficient, but expensive for the buyer. The SOE appeared superior to the FRO and ENG. The clock improves efficiency over the FRO while less information kept prices under the ENG. The MUV was superior in revealing costs

A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

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Vineeth Rajan

2014-01-01

Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

Programmed necrosis and necroptosis – molecular mechanisms

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Agata Giżycka

2015-12-01

Full Text Available Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Management of Klippel-Trenauny syndrome with multiple organ involvement

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Nassiri Javad

2007-01-01

Full Text Available Klippel-Trenauny syndrome is a disturbance in the development of the mesodermal and ectodermal tissues occurring in utero, which is characterized by vascular nevi, varicose veins, soft tissue, and occasionally, bone hyperplasia. Our patient is a 6-year-old boy with presentation of left lower extremity over growth, abdominal mass, abdominal pain, bilateral buttock mass, rectal bleeding, and skin hemangiomatosis. The major problems of this case were involvement of the levator ani, external anal sphincter, and encasement of the sciatic nerves within the buttock mass. We concluded that the use of muscle and nerve stimulator for detection and saving sphincters and the nerves in these cases could improve the results of surgical resection.

Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

International Nuclear Information System (INIS)

Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

2014-01-01

Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

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Jun eWang

2014-03-01

Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens.

Science.gov (United States)

Bardo, M T

1998-01-01

Multiple lines of research have implicated the mesolimbic dopamine system in drug reward measured by either the drug self-administration or conditioned place preference paradigm. The present review summarizes recent work that examines the neuropharmacological mechanisms by which drugs impinge on this dopaminergic neural circuitry, as well as other systems that provide input and output circuits to the mesolimbic dopamine system. Studies examining the effect of selective agonist and antagonist drugs administered systemically have indicated that multiple neurotransmitters are involved, including dopamine, serotonin, acetylcholine, glutamate, GABA, and various peptides. Direct microinjection studies have also provided crucial evidence indicating that, in addition to the mesolimbic dopamine system, other structures play a role in drug reward, including the ventral pallidum, amygdala, hippocampus, hypothalamus, and pedunculopontine tegmental nucleus. GABAergic circuitry descending from the nucleus accumbens to the pedunculopontine tegmental nucleus via the ventral pallidum appears to be especially important in directing the behavioral sequelae associated with reward produced by various drugs of abuse. However, activation of the reward circuitry is achieved differently for various drugs of abuse. With amphetamine and cocaine, initiation of reward is controlled within the nucleus accumbens and prefrontal cortex, respectively. With opiates, initiation of reward involves the ventral tegmental area, nucleus accumbens, hippocampus, and hypothalamus. It is not clear presently if these multiple anatomical structures mediate opiate reward by converging on a single output system or multiple output systems.

Managing Supplier Involvement in New Product Development: A Multiple-Case Study

NARCIS (Netherlands)

F.E.A. van Echtelt (Ferrie); J.Y.F. Wynstra (Finn); A.J. van Weele (Arjan); G.M. Duysters (Geert)

2006-01-01

textabstractExisting studies of supplier involvement in new product development have mainly focused on project-related short-term processes and success-factors. This study validates and extends an existing exploratory framework, which comprises both long-term strategic processes and short-term

Managing supplier involvement in new product development : a multiple-case study

NARCIS (Netherlands)

Echtelt, van F.E.A.; Wynstra, J.Y.F.; Weele, van A.J.; Duysters, G.M.

2008-01-01

Existing studies of supplier involvement in new product development have mainly focused on project-related short-term processes and success factors. This study validates and extends an existing exploratory framework, which comprises both long-term strategic processes and short-term operational

Multiple-Symbol, Partially Coherent Detection of MPSK

Science.gov (United States)

Simon, Marvin K.; Divsalar, Dariush

1994-01-01

Proposed method of reception of multiple-phase-shift-keyed (MPSK) radio signals involves multiple-symbol, partially coherent detection. Instead of attempting to determine phase of transmitted signal during each symbol period as in coherent detection, receiver acquires signal data during multiple-symbol observation interval, then produces maximum-likelihood-sequence estimate of phases transmitted during interval. Combination of coherent-reception and incoherent-reception decision rules are used.

A rare condition of anorectal dysfunction in a patient with multiple sclerosis: Coexistence of faecal incontinence and mechanical constipation: Report of case.

Science.gov (United States)

Dandin, Özgür; Akpak, Yaşam Kemal; Karakaş, Dursun Özgür; Hazer, Batuhan; Ergin, Tuncer; Dandinoğlu, Taner; Teomete, Uygar

2014-01-01

Multiple sclerosis is a chronic demyelinating neurological disease and causing a variety of neurological symptoms, including discomfort of anorectal function. Constipation and faecal incontinence present as anorectal dysfunction in MS and anal manometry, colonic transit time, electromyography, and defecography can be used for assessment. We presented a thirty-three years old woman with rare condition of anorectal dysfunction in multiple sclerosis. Anal manometry, defecography were done, and synchronously anal incontinence and mechanical constipation due to rectocele and anismus were detected in this patient. Although anal incontinence and constipation are seen often in patients with multiple sclerosis, in the literature, coexistence of animus, rectocele and anal incontinence are quite rare. Defecography and anal manometry are useful diagnostic methods for demonstration of anorectal dysfuntions in patients with MS. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave tequilana Weber and Agave angustifolia Haw.

Science.gov (United States)

Gómez-Rodríguez, Víctor Manuel; Rodríguez-Garay, Benjamín; Barba-Gonzalez, Rodrigo

2012-01-01

A cytological analysis of the microsporogenesis was carried out in the Agave tequilana and A. angustifolia species. Several abnormalities such as chromosomal bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found. The morphological analysis of the pollen, together with the above-mentioned 2n microspores, allowed us to confirm the presence of 2n pollen as well as its frequency. In both A. tequilana and A. angustifolia two different mechanisms were observed: the first mechanism, a failure in the cytokinesis in meiosis II caused the formation of dyads with two 2n cells and triads containing two n cells and one 2n cell; the second mechanism, involves an abnormal spindle, which caused the formation of triads with two n cells and one 2n cell. Likewise, the presence of monads was detected in both species, these, might be caused by a failure of the cytokinesis in both meiotic divisions. This is the first report about the presence of a Second Division Restitution mechanism (SDR) which causes the formation of 2n pollen in the genus Agave. The genetic implications of the presence of 2n pollen in the genus Agave are discussed.

How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

Science.gov (United States)

Singh, Amit; Kar, Sujita Kumar

2017-01-01

Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

Prediction of mechanical fatigue caused by multiple random excitations

NARCIS (Netherlands)

Bonte, M.H.A.; de Boer, Andries; Liebregts, R.

2004-01-01

A simulation method is presented for the fatigue analysis of automotive and other products that are subjected to multiple random excitations. The method is denoted as frequency domain stress-life fatigue analysis and was implemented in the automotive industry at DAF Trucks N.V. in Eindhoven, The

Mechanisms Design

DEFF Research Database (Denmark)

Restrepo-Giraldo, John Dairo

2006-01-01

Most products and machines involve some kind of controlled movement. From window casements to DVD players, from harbor cranes to the shears to prune your garden, all these machines require mechanisms to move. This course intends to provide the analytical and conceptual tools to design such mechan......Most products and machines involve some kind of controlled movement. From window casements to DVD players, from harbor cranes to the shears to prune your garden, all these machines require mechanisms to move. This course intends to provide the analytical and conceptual tools to design...... using criteria such as size, performance parameters, operation environment, etc. Content: Understanding Mechanisms Design (2 weeks) Definitions, mechanisms representations, kinematic diagrams, the four bar linkage, mobility, applications of mechanisms, types of mechanisms, special mechanisms, the design......: equations for various mechanisms. At the end of this module you will be able to analyze existing mechanisms and to describe their movement. Designing mechanisms (7 weeks) Type synthesis and dimensional synthesis, function generation, path generation, three precision points in multi-loop mechanisms...

Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients.

Directory of Open Access Journals (Sweden)

Anne Waschbisch

Full Text Available Immunoglobulin-like transcript (ILT 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue. We also studied the ability of interferon beta, alone or in combination with vitamin D, to induce upregulation of these receptors in vitro, and compared expression levels between interferon-treated and untreated multiple sclerosis patients. In vitro interferon beta treatment led to a robust upregulation of ILT3 and ILT4 on monocytes, and dihydroxyvitamin D3 increased expression of ILT3 but not ILT4. ILT3 was abundant in demyelinating lesions in postmortem brain, and expression on monocytes in the cerebrospinal fluid was higher than in peripheral blood, suggesting that the central nervous system milieu induces ILT3, or that ILT3 positive monocytes preferentially enter the brain. Our data are consistent with involvement of ILT3 and ILT4 in the modulation of immune responsiveness in multiple sclerosis by both interferon and vitamin D.

Differences between Homicides Committed by Lone and Multiple Offenders in Korea.

Science.gov (United States)

Park, Jisun; Cho, Joon Tag

2018-05-16

The aim of this study was to differentiate between homicides committed by multiple offenders and homicides committed by lone offenders. Using data on homicide incidents that occurred in South Korea between 1985 and 2008, we compared 134 homicides committed by multiple offenders, with 369 homicides committed by lone offenders. A greater proportion of homicides committed by multiple offenders involved injuries to the victim's head compared to homicides by lone offenders. Homicides committed by multiple offenders were more likely to involve blunt instruments and ligatures, whereas homicides by lone offenders were more likely to involve sharp instruments. In addition, a majority of the homicides committed by multiple offenders were planned. The results of this study have practical implications for homicide investigations, as well as theoretical implications for homicide research on the difference in offense behaviors based on the number of offenders. © 2018 American Academy of Forensic Sciences.

Elder Care, Multiple Role Involvement, and Well-Being Among Middle-Aged Men and Women in Japan.

Science.gov (United States)

Kikuzawa, Saeko

2015-12-01

Japan's population is aging at an unprecedented rate. Combined with the tradition of family responsibility for elder care, this rapid population aging has resulted in middle-aged Japanese people being much more likely today than in past decades to face the responsibility of caring for their elderly parents alongside their other major roles. Using nationally representative Japanese data, this study assessed the individual and combined implications of caregiving and other role involvements for the well-being of middle-aged men and women. Some evidence was found for deleterious psychological consequences of the caregiver role. However, in contrast to expectations, the interaction between the roles of caregiver and worker was positively associated with well-being among both men and women. The results suggest the importance of middle-aged adults being able to keep working when they have to care for their aging parents. Another important finding was significant gender differences in the psychological consequences of holding multiple family- and work-related roles and in combining these with the caregiver role. Further analysis showed that the spousal role was also negatively associated with depressive symptoms and positively associated with satisfaction for men but not for women. Gender differences in the findings appear to reflect the significant gender asymmetry in role experiences in Japan.

Accounting for multiple births in randomised trials: a systematic review.

Science.gov (United States)

Yelland, Lisa Nicole; Sullivan, Thomas Richard; Makrides, Maria

2015-03-01

Multiple births are an important subgroup to consider in trials aimed at reducing preterm birth or its consequences. Including multiples results in a unique mixture of independent and clustered data, which has implications for the design, analysis and reporting of the trial. We aimed to determine how multiple births were taken into account in the design and analysis of recent trials involving preterm infants, and whether key information relevant to multiple births was reported. We conducted a systematic review of multicentre randomised trials involving preterm infants published between 2008 and 2013. Information relevant to multiple births was extracted. Of the 56 trials included in the review, 6 (11%) excluded multiples and 24 (43%) failed to indicate whether multiples were included. Among the 26 trials that reported multiples were included, only one (4%) accounted for clustering in the sample size calculations and eight (31%) took the clustering into account in the analysis of the primary outcome. Of the 20 trials that randomised infants, 12 (60%) failed to report how infants from the same birth were randomised. Information on multiple births is often poorly reported in trials involving preterm infants, and clustering due to multiple births is rarely taken into account. Since ignoring clustering could result in inappropriate recommendations for clinical practice, clustering should be taken into account in the design and analysis of future neonatal and perinatal trials including infants from a multiple birth. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

May Diet and Dietary Supplements Improve the Wellness of Multiple Sclerosis Patients? A Molecular Approach

Directory of Open Access Journals (Sweden)

Paolo Riccio

2010-01-01

Full Text Available Multiple sclerosis is a complex and multifactorial neurological disease, and nutrition is one of the environmental factors possibly involved in its pathogenesis. At present, the role of nutrition is unclear, and MS therapy is not associated to a particular diet. MS clinical trials based on specific diets or dietary supplements are very few and in some cases controversial. To understand how diet can influence the course of MS and improve the wellness of MS patients, it is necessary to identify the dietary molecules, their targets and the molecular mechanisms involved in the control of the disease. The aim of this paper is to provide a molecular basis for the nutritional intervention in MS by evaluating at molecular level the effect of dietary molecules on the inflammatory and autoimmune processes involved in the disease.

Erector spinae plane block may aid weaning from mechanical ventilation in patients with multiple rib fractures: Case report of two cases

Directory of Open Access Journals (Sweden)

Amar Nandhakumar

2018-01-01

Full Text Available Uncontrolled pain in patients with rib fracture leads to atelectasis and impaired cough which can progress to pneumonia and respiratory failure necessitating mechanical ventilation. Of the various pain modalities, regional anaesthesia (epidural and paravertebral is better than systemic and oral analgesics. The erector spinae plane block (ESPB is a new modality in the armamentarium for the management of pain in multiple rib fractures, which is simple to perform and without major complications. We report a case series where ESPB helped in weaning the patients from mechanical ventilation. Further randomised controlled studies are warranted in comparing their efficacy in relation to other regional anaesthetic techniques.

Interfacial Mechanics Analysis of a Brittle Coating–Ductile Substrate System Involved in Thermoelastic Contact

Directory of Open Access Journals (Sweden)

Chi Zhang

2017-02-01

Full Text Available In this paper, interfacial stress analysis for a brittle coating/ductile substrate system, which is involved in a sliding contact with a rigid ball, is presented. By combining interface mechanics theory and the image point method, stress and displacement responses within a coated material for normal load, tangential load, and thermal load are obtained; further, the Green’s functions are established. The effects of coating thickness, friction coefficient, and a coating’s thermoelastic properties on the interfacial shear stress, τxz, and transverse stress, σxx, distributions are discussed in detail. A phenomenon, where interfacial shear stress tends to be relieved by frictional heating, is found in the case of a coating material’s thermal expansion coefficient being less than a substrate material’s thermal expansion coefficient. Additionally, numerical results show that distribution of interfacial stress can be altered and, therefore, interfacial damage can be modified by adjusting a coating’s structural parameters and thermoelastic properties.

Defense Mechanisms: A Bibliography.

Science.gov (United States)

Pedrini, D. T.; Pedrini, Bonnie C.

This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

Insertion of molecular oxygen into a palladium(II) methyl bond: a radical chain mechanism involving palladium(III) intermediates.

Science.gov (United States)

Boisvert, Luc; Denney, Melanie C; Hanson, Susan Kloek; Goldberg, Karen I

2009-11-04

The reaction of (bipy)PdMe(2) (1) (bipy = 2,2'-bipyridine) with molecular oxygen results in the formation of the palladium(II) methylperoxide complex (bipy)PdMe(OOMe) (2). The identity of the product 2 has been confirmed by independent synthesis. Results of kinetic studies of this unprecedented oxygen insertion reaction into a palladium alkyl bond support the involvement of a radical chain mechanism. Reproducible rates, attained in the presence of the radical initiator 2,2'-azobis(2-methylpropionitrile) (AIBN), reveal that the reaction is overall first-order (one-half-order in both [1] and [AIBN], and zero-order in [O(2)]). The unusual rate law (half-order in [1]) implies that the reaction proceeds by a mechanism that differs significantly from those for organic autoxidations and for the recently reported examples of insertion of O(2) into Pd(II) hydride bonds. The mechanism for the autoxidation of 1 is more closely related to that found for the autoxidation of main group and early transition metal alkyl complexes. Notably, the chain propagation is proposed to proceed via a stepwise associative homolytic substitution at the Pd center of 1 with formation of a pentacoordinate Pd(III) intermediate.

Multiscale modelling of DNA mechanics

International Nuclear Information System (INIS)

Dršata, Tomáš; Lankaš, Filip

2015-01-01

Mechanical properties of DNA are important not only in a wide range of biological processes but also in the emerging field of DNA nanotechnology. We review some of the recent developments in modeling these properties, emphasizing the multiscale nature of the problem. Modern atomic resolution, explicit solvent molecular dynamics simulations have contributed to our understanding of DNA fine structure and conformational polymorphism. These simulations may serve as data sources to parameterize rigid base models which themselves have undergone major development. A consistent buildup of larger entities involving multiple rigid bases enables us to describe DNA at more global scales. Free energy methods to impose large strains on DNA, as well as bead models and other approaches, are also briefly discussed. (topical review)

Alpha-particles induce autophagy in multiple myeloma cells

Directory of Open Access Journals (Sweden)

Joelle Marcelle Gaschet

2015-10-01

Full Text Available Objectives: Radiations emitted by the radionuclides in radioimmunotherapy (RIT approaches induce direct killing of the targeted cells as well as indirect killing through bystander effect. Our research group is dedicated to the development of α-RIT, i.e RIT using α-particles especially for the treatment of multiple myeloma (MM. γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by 213Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of 213Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.Methods: Murine 5T33 and human LP-1 multiple myeloma (MM cell lines were used to study the effects of such α-particles. We first examined the effects of 213Bi on proliferation rate, double strand DNA breaks, cell cycle and cell death. Then, we investigated autophagy after 213Bi irradiation. Finally, a co-culture of dendritic cells (DC with irradiated tumour cells or their culture media was performed to test whether it would induce DC activation.Results: We showed that 213Bi induces DNA double strand breaks, cell cycle arrest and autophagy in both cell lines but we detected only slight levels of early apoptosis within the 120 hours following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented 213Bi induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s, however no increase in membrane or extracellular expression of danger associated molecular patterns (DAMPs was observed after irradiation.Conclusion: This study demonstrates that 213Bi induces mainly necrosis in MM cells, low levels of apoptosis and also autophagy that might be involved in tumor cell death.

Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

Science.gov (United States)

Taylor, Beth A; Thompson, Paul D

2015-06-01

This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

Multiple cis-acting elements involved in up-regulation of a cytochrome P450 gene conferring resistance to deltamethrin in smal brown planthopper, Laodelphax striatellus (Fallén).

Science.gov (United States)

Pu, Jian; Sun, Haina; Wang, Jinda; Wu, Min; Wang, Kangxu; Denholm, Ian; Han, Zhaojun

2016-11-01

As well as arising from single point mutations in binding sites or detoxifying enzymes, it is likely that insecticide resistance mechanisms are frequently controlled by multiple genetic factors, resulting in resistance being inherited as a quantitative trait. However, empirical evidence for this is still rare. Here we analyse the causes of up-regulation of CYP6FU1, a monoxygenase implicated in resistance to deltamethrin in the rice pest Laodelphax striatellus. The 5'-flanking region of this gene was cloned and sequenced from individuals of a susceptible and a resistant strain. A luminescent reporter assay was used to evaluate different 5'-flanking regions and their fragments for promoter activity. Mutations enhancing promoter activity in various fragments were characterized, singly and in combination, by site mutation recovery. Nucleotide diversity in flanking sequences was greatly reduced in deltamethrin-resistant insects compared to susceptible ones. Phylogenetic sequence analysis found that CYP6FU1 had five different types of 5'-flanking region. All five types were present in a susceptible strain but only a single type showing the highest promoter activity was present in a resistant strain. Four cis-acting elements were identified whose influence on up-regulation was much more pronounced in combination than when present singly. Of these, two were new transcription factor (TF) binding sites produced by mutations, another one was also a new TF binding site alternated from an existing one, and the fourth was a unique transcription start site. These results demonstrate that multiple cis-acting elements are involved in up-regulating CYP6FU1 to generate a resistance phenotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neurological manifestaions among Sudanese patients with multiple ...

African Journals Online (AJOL)

Background: Multiple myeloma may involve the nervous system at every level, including the neuromuscular junction, peripheral nerve, plexus, spinal nerve root, spinal cord, meninges, and brain. Such involvement may be primary or secondary, as well as non-invasive paraneoplastic effects. Objective: To find out the ...

Primary laryngeal localization of multiple myeloma: A case report

OpenAIRE

Allegra, Eugenia; Marino, Nicol?; Modica, Domenico; Emmanuele, Carmela; Saita, Vincenzo

2017-01-01

Multiple myeloma is a lymphoproliferative disease that may involve the bone marrow as well as extramedullary soft tissues. However, laryngeal localization of multiple myeloma is extremely rare. We herein present the case of a 68-year-old male patient with a history of dyspnea, dysphonia and dysphagia. Laryngoscopic examination revealed a lesion involving the right glottis and right vestibular (false) vocal fold, with absence of ipsilateral laryngeal motility and constriction of the airway. Co...

Microarray Analysis of the Molecular Mechanism Involved in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Cheng Tan

2018-01-01

Full Text Available Purpose. This study aimed to investigate the underlying molecular mechanisms of Parkinson’s disease (PD by bioinformatics. Methods. Using the microarray dataset GSE72267 from the Gene Expression Omnibus database, which included 40 blood samples from PD patients and 19 matched controls, differentially expressed genes (DEGs were identified after data preprocessing, followed by Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analyses. Protein-protein interaction (PPI network, microRNA- (miRNA- target regulatory network, and transcription factor- (TF- target regulatory networks were constructed. Results. Of 819 DEGs obtained, 359 were upregulated and 460 were downregulated. Two GO terms, “rRNA processing” and “cytoplasm,” and two KEGG pathways, “metabolic pathways” and “TNF signaling pathway,” played roles in PD development. Intercellular adhesion molecule 1 (ICAM1 was the hub node in the PPI network; hsa-miR-7-5p, hsa-miR-433-3p, and hsa-miR-133b participated in PD pathogenesis. Six TFs, including zinc finger and BTB domain-containing 7A, ovo-like transcriptional repressor 1, GATA-binding protein 3, transcription factor dp-1, SMAD family member 1, and quiescin sulfhydryl oxidase 1, were related to PD. Conclusions. “rRNA processing,” “cytoplasm,” “metabolic pathways,” and “TNF signaling pathway” were key pathways involved in PD. ICAM1, hsa-miR-7-5p, hsa-miR-433-3p, hsa-miR-133b, and the abovementioned six TFs might play important roles in PD development.

Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide

International Nuclear Information System (INIS)

Kurokawa, Yuko; Sekiguchi, Fumiko; Kubo, Satoko; Yamasaki, Yoshiko; Matsuda, Sachi; Okamoto, Yukari; Sekimoto, Teruki; Fukatsu, Anna; Nishikawa, Hiroyuki; Kume, Toshiaki; Fukushima, Nobuyuki; Akaike, Akinori; Kawabata, Atsufumi

2011-01-01

Highlights: ► Hydrogen sulfide causes NMDA receptor-independent neurotoxicity in mouse fetal cortical neurons. ► Activation of ERK mediates the toxicity of hydrogen sulfide. ► Apoptotic mechanisms are involved in the hydrogen-induced cell death. -- Abstract: Hydrogen sulfide (H 2 S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H 2 S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H 2 S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.

Unidirectional, dual-comb lasing under multiple pulse formation mechanisms in a passively mode-locked fiber ring laser

Science.gov (United States)

Liu, Ya; Zhao, Xin; Hu, Guoqing; Li, Cui; Zhao, Bofeng; Zheng, Zheng

2016-09-01

Dual-comb lasers from which asynchronous ultrashort pulses can be simultaneously generated have recently become an interesting research subject. They could be an intriguing alternative to the current dual-laser optical-frequency-comb source with highly sophisticated electronic control systems. If generated through a common light path traveled by all pulses, the common-mode noises between the spectral lines of different pulse trains could be significantly reduced. Therefore, coherent dual-comb generation from a completely common-path, unidirectional lasing cavity would be an interesting territory to explore. In this paper, we demonstrate such a dual-comb lasing scheme based on a nanomaterial saturable absorber with additional pulse narrowing and broadening mechanisms concurrently introduced into a mode-locked fiber laser. The interactions between multiple soliton formation mechanisms result in unusual bifurcation into two-pulse states with quite different characteristics. Simultaneous oscillation of pulses with four-fold difference in pulsewidths and tens of Hz repetition rate difference is observed. The coherence between these spectral-overlapped, picosecond and femtosecond pulses is further verified by the corresponding asynchronous cross-sampling and dual-comb spectroscopy measurements.

Dual Headquarters Involvement in Subsidiary Innovation

DEFF Research Database (Denmark)

Dellestrand, Henrik; Kappen, Philip; Nell, Phillip Christopher

2014-01-01

The strategy and international business literature has identified the overall potential for headquarters to add value by allocating resources to subsidiary activities, but little is known about the extent to which multiple headquarters simultaneously involves itself in subsidiary operations....... The current paper takes on this neglected question by empirically investigating corporate and divisional headquarters direct involvement in innovation development projects at the subsidiary level. Analyses that draw upon 85 innovation development projects in 23 multinational enterprises reveal that dual...... of the developing subsidiary positively moderates the two aforementioned effects on dual headquarters involvement in innovation development. The results lend support for the notion that parenting in complex structures entails complex headquarters structures. Thus, the results question simplistic views...

Measurement and Analysis of Multiple Output Transient Propagation in BJT Analog Circuits

Science.gov (United States)

Roche, Nicolas J.-H.; Khachatrian, A.; Warner, J. H.; Buchner, S. P.; McMorrow, D.; Clymer, D. A.

2016-08-01

The propagation of Analog Single Event Transients (ASETs) to multiple outputs of Bipolar Junction Transistor (BJTs) Integrated Circuits (ICs) is reported for the first time. The results demonstrate that ASETs can appear at several outputs of a BJT amplifier or comparator as a result of a single ion or single laser pulse strike at a single physical location on the chip of a large-scale integrated BJT analog circuit. This is independent of interconnect cross-talk or charge-sharing effects. Laser experiments, together with SPICE simulations and analysis of the ASET's propagation in the s-domain are used to explain how multiple-output transients (MOTs) are generated and propagate in the device. This study demonstrates that both the charge collection associated with an ASET and the ASET's shape, commonly used to characterize the propagation of SETs in devices and systems, are unable to explain quantitatively how MOTs propagate through an integrated analog circuit. The analysis methodology adopted here involves combining the Fourier transform of the propagating signal and the current-source transfer function in the s-domain. This approach reveals the mechanisms involved in the transient signal propagation from its point of generation to one or more outputs without the signal following a continuous interconnect path.

Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

Directory of Open Access Journals (Sweden)

Annett Eitner

2017-11-01

Full Text Available Pain due to osteoarthritis (OA is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate

Notes on the Epidemiology of Multiple Sclerosis, with Special Reference to Dietary Habits

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Lauer, Klaus

2014-01-01

A hypothesis, based primarily on the occurrence of multiple sclerosis (MS) in the Faroe Islands and supported by numerous analytical epidemiological studies, is described. It proposes that MS is caused by the interaction of a virus disease with intestinal pathology, e.g., infectious mononucleosis, and application of smoked and nitrate/nitrite-cured meat products in the diet during circumscribed time intervals. The biological mechanisms might involve a break of tolerance by an alteration of self within the central nervous system, by nitrophenylated compounds conjugated to animal tissue, in particular to proteins occurring in the central nervous system. Further research is needed. PMID:24577315

Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants.

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Korkaric, Muris; Behra, Renata; Fischer, Beat B; Junghans, Marion; Eggen, Rik I L

2015-05-01

The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanisms involved in alleviation of intestinal inflammation by bifidobacterium breve soluble factors.

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Elise Heuvelin

Full Text Available OBJECTIVES: Soluble factors released by Bifidobacterium breve C50 (Bb alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM and other Gram(+ commensal bacteria to dampen inflammatory chemokine secretion. METHODS: TNFalpha-induced chemokine (CXCL8 secretion and alteration of NF-kappaB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. RESULTS: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kappaB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkappaB-alpha molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. CONCLUSIONS: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylations involved in inflammatory processes and by protective conditioning of dendritic cells.

Reward-related learning via multiple memory systems.

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Delgado, Mauricio R; Dickerson, Kathryn C

2012-07-15

The application of a neuroeconomic approach to the study of reward-related processes has provided significant insights in our understanding of human learning and decision making. Much of this research has focused primarily on the contributions of the corticostriatal circuitry, involved in trial-and-error reward learning. As a result, less consideration has been allotted to the potential influence of different neural mechanisms such as the hippocampus or to more common ways in human society in which information is acquired and utilized to reach a decision, such as through explicit instruction rather than trial-and-error learning. This review examines the individual contributions of multiple learning and memory neural systems and their interactions during human decision making in both normal and neuropsychiatric populations. Specifically, the anatomical and functional connectivity across multiple memory systems are highlighted to suggest that probing the role of the hippocampus and its interactions with the corticostriatal circuitry via the application of model-based neuroeconomic approaches may provide novel insights into neuropsychiatric populations that suffer from damage to one of these structures and as a consequence have deficits in learning, memory, or decision making. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

MULTIPLE SCALES FOR SUSTAINABLE RESULTS

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This session will highlight recent research that incorporates the use of multiple scales and innovative environmental accounting to better inform decisions that affect sustainability, resilience, and vulnerability at all scales. Effective decision-making involves assessment at mu...

Primary care physicians' willingness to disclose oncology errors involving multiple providers to patients.

Science.gov (United States)

Mazor, Kathleen; Roblin, Douglas W; Greene, Sarah M; Fouayzi, Hassan; Gallagher, Thomas H

2016-10-01

Full disclosure of harmful errors to patients, including a statement of regret, an explanation, acceptance of responsibility and commitment to prevent recurrences is the current standard for physicians in the USA. To examine the extent to which primary care physicians' perceptions of event-level, physician-level and organisation-level factors influence intent to disclose a medical error in challenging situations. Cross-sectional survey containing two hypothetical vignettes: (1) delayed diagnosis of breast cancer, and (2) care coordination breakdown causing a delayed response to patient symptoms. In both cases, multiple physicians shared responsibility for the error, and both involved oncology diagnoses. The study was conducted in the context of the HMO Cancer Research Network Cancer Communication Research Center. Primary care physicians from three integrated healthcare delivery systems located in Washington, Massachusetts and Georgia; responses from 297 participants were included in these analyses. The dependent variable intent to disclose included intent to provide an apology, an explanation, information about the cause and plans for preventing recurrences. Independent variables included event-level factors (responsibility for the event, perceived seriousness of the event, predictions about a lawsuit); physician-level factors (value of patient-centred communication, communication self-efficacy and feelings about practice); organisation-level factors included perceived support for communication and time constraints. A majority of respondents would not fully disclose in either situation. The strongest predictors of disclosure were perceived personal responsibility, perceived seriousness of the event and perceived value of patient-centred communication. These variables were consistently associated with intent to disclose. To make meaningful progress towards improving disclosure; physicians, risk managers, organisational leaders, professional organisations and

Involvement of thiol-based mechanisms in plant development.

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Rouhier, Nicolas; Cerveau, Delphine; Couturier, Jérémy; Reichheld, Jean-Philippe; Rey, Pascal

2015-08-01

Increasing knowledge has been recently gained regarding the redox regulation of plant developmental stages. The current state of knowledge concerning the involvement of glutathione, glutaredoxins and thioredoxins in plant development is reviewed. The control of the thiol redox status is mainly ensured by glutathione (GSH), a cysteine-containing tripeptide and by reductases sharing redox-active cysteines, glutaredoxins (GRXs) and thioredoxins (TRXs). Indeed, thiol groups present in many regulatory proteins and metabolic enzymes are prone to oxidation, ultimately leading to post-translational modifications such as disulfide bond formation or glutathionylation. This review focuses on the involvement of GSH, GRXs and TRXs in plant development. Recent studies showed that the proper functioning of root and shoot apical meristems depends on glutathione content and redox status, which regulate, among others, cell cycle and hormone-related processes. A critical role of GRXs in the formation of floral organs has been uncovered, likely through the redox regulation of TGA transcription factor activity. TRXs fulfill many functions in plant development via the regulation of embryo formation, the control of cell-to-cell communication, the mobilization of seed reserves, the biogenesis of chloroplastic structures, the metabolism of carbon and the maintenance of cell redox homeostasis. This review also highlights the tight relationships between thiols, hormones and carbon metabolism, allowing a proper development of plants in relation with the varying environment and the energy availability. GSH, GRXs and TRXs play key roles during the whole plant developmental cycle via their antioxidant functions and the redox-regulation of signaling pathways. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

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Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

2016-10-01

As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Optical transitions involving unconfined energy states in In/sub x/Ga/sub 1-//sub x/As/GaAs multiple quantum wells

International Nuclear Information System (INIS)

Ji, G.; Dobbelaere, W.; Huang, D.; Morkoc, H.

1989-01-01

Optical transitions with energies higher than that of the GaAs band gap in highly strained In/sub x/Ga/sub 1-//sub x/As/GaAs multiple--quantum-well structures have been observed in photoreflectance spectra. In some samples as many as seven such structures were present. We identify them as transitions between the unconfined electron states and the confined heavy-hole states. For energies below the GaAs signal, intense transitions corresponding to such unconfined electron subbands were also observed. The intensity of the transitions involving unconfined electron subbands decreases with increasing well width, but is weakly dependent on the mole fraction x. The transmission coefficients are calculated in order to locate the positions of the unconfined electron subband energies. Good agreement is obtained between the experimental data and the theoretical calculation

Study of the Chemical Mechanism Involved in the Formation of Tungstite in Benzyl Alcohol by the Advanced QEXAFS Technique

DEFF Research Database (Denmark)

Olliges‐Stadler, Inga; Stötzel, Jan; Koziej, Dorota

2012-01-01

Insight into the complex chemical mechanism for the formation of tungstite nanoparticles obtained by the reaction of tungsten hexachloride with benzyl alcohol is presented herein. The organic and inorganic species involved in the formation of the nanoparticles were studied by time‐dependent gas......‐scanning extended X‐ray absorption fine structure spectroscopy enabled the time‐dependent evolution of the starting compound, the intermediates and the product to be monitored over the full reaction period. The reaction starts with fast chlorine substitution and partial reduction during the dissolution...

The ectomycorrhizal fungus Paxillus involutus converts organic matter in plant litter using a trimmed brown-rot mechanism involving Fenton chemistry

DEFF Research Database (Denmark)

Rineau, Francois; Roth, Doris; Shah, Firoz

2012-01-01

chemistry similar to that of brown-rot fungi. The set of enzymes expressed by Pa. involutus during the degradation of the organic matter was similar to the set of enzymes involved in the oxidative degradation of wood by brown-rot fungi. However, Pa. involutus lacked transcripts encoding extracellular...... the mycorrhizal fungi. To capture the nitrogen, the fungi must at least partly disrupt the recalcitrant organic matterprotein complexes within which the nitrogen is embedded. This disruption process is poorly characterized. We used spectroscopic analyses and transcriptome profiling to examine the mechanism...... by which the ectomycorrhizal fungus Paxillus involutus degrades organic matter when acquiring nitrogen from plant litter. The fungus partially degraded polysaccharides and modified the structure of polyphenols. The observed chemical changes were consistent with a hydroxyl radical attack, involving Fenton...

Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

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Carlo Travaglini-Allocatelli

2013-01-01

Full Text Available Cytochromes c (Cyt c are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i heme translocation and delivery, (ii apoCyt thioreductive pathway, and (iii apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

Tokamak engineering mechanics

International Nuclear Information System (INIS)

Song, Yuntao; Wu, Weiyue; Du, Shijun

2014-01-01

Provides a systematic introduction to tokamaks in engineering mechanics. Includes design guides based on full mechanical analysis, which makes it possible to accurately predict load capacity and temperature increases. Presents comprehensive information on important design factors involving materials. Covers the latest advances in and up-to-date references on tokamak devices. Numerous examples reinforce the understanding of concepts and provide procedures for design. Tokamak Engineering Mechanics offers concise and thorough coverage of engineering mechanics theory and application for tokamaks, and the material is reinforced by numerous examples. Chapter topics include general principles, static mechanics, dynamic mechanics, thermal fluid mechanics and multiphysics structural mechanics of tokamak structure analysis. The theoretical principle of the design and the methods of the analysis for various components and load conditions are presented, while the latest engineering technologies are also introduced. The book will provide readers involved in the study of mechanical/fusion engineering with a general understanding of tokamak engineering mechanics.

Learning models of activities involving interacting objects

DEFF Research Database (Denmark)

Manfredotti, Cristina; Pedersen, Kim Steenstrup; Hamilton, Howard J.

2013-01-01

We propose the LEMAIO multi-layer framework, which makes use of hierarchical abstraction to learn models for activities involving multiple interacting objects from time sequences of data concerning the individual objects. Experiments in the sea navigation domain yielded learned models that were t...

Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

International Nuclear Information System (INIS)

Bull, R.J.; Miller, J.H.; Sasser, L.B.; Schultz, I.R.; Thrall, B.D.

1998-01-01

'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax infection.

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Flávia Carolina F de Araujo

Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.

Multiple shadows from distorted static black holes

Science.gov (United States)

Grover, Jai; Kunz, Jutta; Nedkova, Petya; Wittig, Alexander; Yazadjiev, Stoytcho

2018-04-01

We study the local shadow of the Schwarzschild black hole with a quadrupole distortion and the influence of the external gravitational field on the photon dynamics. The external matter sources modify the light ring structure and lead to the appearance of multiple shadow images. In the case of negative quadrupole moments we identify the most prominent mechanism causing multiple shadow formation. Furthermore, we obtain a condition under which this mechanism can be realized. This condition depends on the quadrupole moment, but also on the position of the observer and the celestial sphere.

A Glance on Diagnosis and Ttreatment of Profound Fatigue in Multiple Sclerosis

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Mojtaba Azimian

2007-09-01

Full Text Available Multiple Sclerosis (M.S is one of the prevalent diseases of the central nervous system which cause disability in young adults. This appears as neural signs in different parts and various times. The main defect is local deterioration or destruction of myelin tissue in the brain and spinal cord. Profound fatigue is one the most common symptoms of this disease. Because MS is prevalent in middle ages, so the presence of this symptom affects the life and activity of the patient In these ages people have high amount of activities and this functional disorder creates many difficulties for daily works in patient. For this reason, fatigue problem in patients, always, have caught the attention of researchers. Despite numerous studies, still the exact reason for producing fatigue have not been mentioned But several mechanisms have been discussed, such as: autoimmune mechanism of the disease, Involvement and disorder of endocrine system, involvement of central nervous system and de-synchronization of autonom system. Among these, autoimmune mechanism is considered as a main role in producing fatigue. Lack of proper knowledge regarding exact fatigue mechanism several problems in its treatment. Evaluation is the first step for controlling fatigue, which is done through various tests. Clear and proper evaluation can be obtained by these tests. After evaluation, non-drug and finally drug procedures are helpful. In non-drug treatment the focus is on: sport exercises, suitable diet program, identification and improvement of the patient psychotic disorders, energy conservation methods. Finally, the use of drugs such as Amantadine, Pemoline and Modafini is recommended for fatigue treatment.

Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions

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Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A.; Decker, William; Manjili, Masoud H.; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth P.; Brown, Dustin G.; Lowe, Leroy; Lyerly, H.Kim

2015-01-01

An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. PMID:26002081

A quantized mechanism for activation of pannexin channels

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Chiu, Yu-Hsin; Jin, Xueyao; Medina, Christopher B.; Leonhardt, Susan A.; Kiessling, Volker; Bennett, Brad C.; Shu, Shaofang; Tamm, Lukas K.; Yeager, Mark; Ravichandran, Kodi S.; Bayliss, Douglas A.

2017-01-01

Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer. Progressive PANX1 channel opening is directly linked to permeation of ions and large molecules (ATP and fluorescent dyes) and occurs during both irreversible (caspase cleavage-mediated) and reversible (α1 adrenoceptor-mediated) forms of channel activation. This unique, quantized activation process enables fine tuning of PANX1 channel activity and may be a generalized regulatory mechanism for other related multimeric channels. PMID:28134257

Basic dynamics at a multiple resonance

International Nuclear Information System (INIS)

Ferraz-Mello, S.; Yokoyama, T.

The problem of multiple resonance is dealt with as it occurs in Celestial Mechanics and in non-linear Mechanics. In perturbation theory small divisors occur as a consequence of the fact that the flows in the phase space of the real system and the flows in the phase space of the so-called undisturbed system are not homeomorphic at all. Whatever the perturbation technique we adopt, the first step is to correct the topology of the undisturbed flows. It is shown that at a multiple resonance we are led to dynamical systems that are generally non-integrable. The basic representatives of these systems are the n-pendulums theta sup(:) sub(k) = σ sub(j)A sub(jk) sin theta sub(j). Multiple resonances are classified as syndetic or asyndetic following the eigenvalues of a quadratic form. Some degenerate cases are also presented. (Author) [pt

Numerical solution of fractured horizontal wells in shale gas reservoirs considering multiple transport mechanisms

Science.gov (United States)

Zhao, Yu-long; Tang, Xu-chuan; Zhang, Lie-hui; Tang, Hong-ming; Tao, Zheng-Wu

2018-06-01

The multiscale pore size and specific gas storage mechanism in organic-rich shale gas reservoirs make gas transport in such reservoirs complicated. Therefore, a model that fully incorporates all transport mechanisms and employs an accurate numerical method is urgently needed to simulate the gas production process. In this paper, a unified model of apparent permeability was first developed, which took into account multiple influential factors including slip flow, Knudsen diffusion (KD), surface diffusion, effects of the adsorbed layer, permeability stress sensitivity, and ad-/desorption phenomena. Subsequently, a comprehensive mathematical model, which included the model of apparent permeability, was derived to describe gas production behaviors. Thereafter, on the basis of unstructured perpendicular bisection grids and finite volume method, a fully implicit numerical simulator was developed using Matlab software. The validation and application of the new model were confirmed using a field case reported in the literature. Finally, the impacts of related influencing factors on gas production were analyzed. The results showed that KD resulted in a negligible impact on gas production in the proposed model. The smaller the pore size was, the more obvious the effects of the adsorbed layer on the well production rate would be. Permeability stress sensitivity had a slight effect on well cumulative production in shale gas reservoirs. Adsorbed gas made a major contribution to the later flow period of the well; the greater the adsorbed gas content, the greater the well production rate would be. This paper can improve the understanding of gas production in shale gas reservoirs for petroleum engineers.

Cancer cachexia, mechanism and treatment

Science.gov (United States)

Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Matsubara, Hisahiro; Takabe, Kazuaki

2015-01-01

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials. PMID:25897346

Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

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Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

2011-01-01

Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

QTL analysis of frost damage in pea suggests different mechanisms involved in frost tolerance.

Science.gov (United States)

Klein, Anthony; Houtin, Hervé; Rond, Céline; Marget, Pascal; Jacquin, Françoise; Boucherot, Karen; Huart, Myriam; Rivière, Nathalie; Boutet, Gilles; Lejeune-Hénaut, Isabelle; Burstin, Judith

2014-06-01

Avoidance mechanisms and intrinsic resistance are complementary strategies to improve winter frost tolerance and yield potential in field pea. The development of the winter pea crop represents a major challenge to expand plant protein production in temperate areas. Breeding winter cultivars requires the combination of freezing tolerance as well as high seed productivity and quality. In this context, we investigated the genetic determinism of winter frost tolerance and assessed its genetic relationship with yield and developmental traits. Using a newly identified source of frost resistance, we developed a population of recombinant inbred lines and evaluated it in six environments in Dijon and Clermont-Ferrand between 2005 and 2010. We developed a genetic map comprising 679 markers distributed over seven linkage groups and covering 947.1 cM. One hundred sixty-one quantitative trait loci (QTL) explaining 9-71 % of the phenotypic variation were detected across the six environments for all traits measured. Two clusters of QTL mapped on the linkage groups III and one cluster on LGVI reveal the genetic links between phenology, morphology, yield-related traits and frost tolerance in winter pea. QTL clusters on LGIII highlighted major developmental gene loci (Hr and Le) and the QTL cluster on LGVI explained up to 71 % of the winter frost damage variation. This suggests that a specific architecture and flowering ideotype defines frost tolerance in winter pea. However, two consistent frost tolerance QTL on LGV were independent of phenology and morphology traits, showing that different protective mechanisms are involved in frost tolerance. Finally, these results suggest that frost tolerance can be bred independently to seed productivity and quality.

Biological pathways and genetic mechanisms involved in social functioning.

Science.gov (United States)

Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G

2013-08-01

To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.

Methodology for the selection of routes for international cross-border line projects involving multiple objectives and decision-makers in the analyses of restrictions and environmental possibilities

International Nuclear Information System (INIS)

Angel S, Enrique; Cadena, Luis Fernando

2005-01-01

A scheme was developed and applied to select the optimum environmental route for international cross-border line projects, in a decision making context involving multiple objectives and multiple decision-makers, the project studied was the electricity interconnection for central America (SIEPAC) for which a prospective assessment was carried out regarding the restrictions and possibilities in the light of the Colombian environmental dimensions management model. The methodology proposed followed these stages: Definition and approval of the structure of environmental restriction and criticality variables, sectorization and selection of complex sections, definition of decision-makers for multi-objective analysis; design and application of consultation tool; definition and modeling of options applying SIG; sensitivity analysis of alternative routes and project's environment management. Different options were identified for insertion and permanence of the project according to the criteria of various interest groups and actors consulted: environmental authorities, electricity companies, scientific community and civil society

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

Directory of Open Access Journals (Sweden)

J. Lozano-Cuenca

Full Text Available Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10–9–10–5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10–7.5–10–5 M. The present outcome was not modified by 10–6 M atropine (an antagonist of muscarinic acetylcholine receptors, 3.1×10–7 M glibenclamide (an ATP-sensitive K+ channel blocker, 10–3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker, 10–5 M indomethacin (a prostaglandin synthesis inhibitor, 10–5 M clotrimazole (a cytochrome P450 inhibitor or 10–5 M cycloheximide (a general protein synthesis inhibitor. Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05 by 10–5 M L-NAME (a direct inhibitor of nitric oxide synthase, 10–7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase, 10–6 M KT 5823 (an inhibitor of protein kinase G, 10–2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker and 10–7 M apamin plus 10–7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively, and was blocked by 8×10–2 M potassium (a high concentration and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Modulation of C. elegans Touch Sensitivity Is Integrated at Multiple Levels

Science.gov (United States)

Chen, Xiaoyin

2014-01-01

Sensory systems can adapt to different environmental signals. Here we identify four conditions that modulate anterior touch sensitivity in Caenorhabditis elegans after several hours and demonstrate that such sensory modulation is integrated at multiple levels to produce a single output. Prolonged vibration involving integrin signaling directly sensitizes the touch receptor neurons (TRNs). In contrast, hypoxia, the dauer state, and high salt reduce touch sensitivity by preventing the release of long-range neuroregulators, including two insulin-like proteins. Integration of these latter inputs occurs at upstream neurohormonal cells and at the insulin signaling cascade within the TRNs. These signals and those from integrin signaling converge to modulate touch sensitivity by regulating AKT kinases and DAF-16/FOXO. Thus, activation of either the integrin or insulin pathways can compensate for defects in the other pathway. This modulatory system integrates conflicting signals from different modalities, and adapts touch sensitivity to both mechanical and non-mechanical conditions. PMID:24806678

Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery

International Nuclear Information System (INIS)

Audsley, Michelle D.; Jans, David A.; Moseley, Gregory W.

2016-01-01

Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion. - Highlights: • A new model for Nipah virus W protein nucleocytoplasmic trafficking is proposed. • Nipah W protein is shown to undergo active nuclear export via exportin-1. • Nipah W nuclear import is mediated by multiple nuclear localisation signals.

Microorganisms involved in MIC

Energy Technology Data Exchange (ETDEWEB)

Sorensen, K. [Danish Technological Institute (Denmark)

2011-07-01

Microbiologically influenced corrosion (MIC) is a widespread problem that is difficult to detect and assess because of its complex mechanism. This paper presents the involvement of microorganisms in MIC. Some of the mechanisms that cause MIC include hydrogen consumption, production of acids, anode-cathode formation and electron shuttling. A classic bio-corrosive microorganism in the oil and gas industry is sulphate-reducing prokaryotes (SRP). Methanogens also increase corrosion rates in metals. Some of the phylogenetic orders detected while studying SRP and methanogens are archaeoglobales, clostridiales, methanosarcinales and methanothermococcus. There were some implications, such as growth of SRP not being correlated with growth of methanogens; methanogens were included in MIC risk assessment. A few examples are used to display how microorganisms are involved in topside corrosion and microbial community in producing wells. From the study, it can be concluded that, MIC risk assessment includes system data and empirical knowledge of the distribution and number of microorganisms in the system.

Causal mediation analysis with multiple causally non-ordered mediators.

Science.gov (United States)

Taguri, Masataka; Featherstone, John; Cheng, Jing

2018-01-01

In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

Sensory-specific clock components and memory mechanisms: investigation with parallel timing.

Science.gov (United States)

Gamache, Pierre-Luc; Grondin, Simon

2010-05-01

A challenge for researchers in the time-perception field is to determine whether temporal processing is governed by a central mechanism or by multiple mechanisms working in concert. Behavioral studies of parallel timing offer interesting insights into the question, although the conclusions fail to converge. Most of these studies focus on the number-of-clocks issue, but the commonality of memory mechanisms involved in time processing is often neglected. The present experiment aims to address a straightforward question: do signals from different modalities marking time intervals share the same clock and/or the same memory resources? To this end, an interval reproduction task involving the parallel timing of two sensory signals presented either in the same modality or in different modalities was conducted. The memory component was tested by manipulating the delay separating the presentation of the target intervals and the moment when the reproduction of one of these began. Results show that there is more variance when only visually marked intervals are presented, and this effect is exacerbated with longer retention delays. Finally, when there is only one interval to process, encoding the interval with signals delivered from two modalities helps to reduce variance. Taken together, these results suggest that the hypothesis stating that there are sensory-specific clock components and memory mechanisms is viable.

Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

Science.gov (United States)

Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

2014-12-01

Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

Science.gov (United States)

Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

2017-01-04

Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of food azo dye tartrazine on learning and memory functions in mice and rats, and the possible mechanisms involved.

Science.gov (United States)

Gao, Yonglin; Li, Chunmei; Shen, Jingyu; Yin, Huaxian; An, Xiulin; Jin, Haizhu

2011-08-01

Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in mice and rats. Animals were administered different doses of tartrazine for a period of 30 d and were evaluated by open-field test, step-through test, and Morris water maze test, respectively. Furthermore, the biomarkers of the oxidative stress and pathohistology were also measured to explore the possible mechanisms involved. The results indicated that tartrazine extract significantly enhanced active behavioral response to the open field, increased the escape latency in Morris water maze test and decreased the retention latency in step-through tests. The decline in the activities of catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) as well as a rise in the level of malonaldehyde (MDA) were observed in the brain of tartrazine-treated rats, and these changes were associated with the brain from oxidative damage. The dose levels of tartrazine in the present study produced a few adverse effects in learning and memory functions in animals. The mechanisms might be attributed to promoting lipid peroxidation products and reactive oxygen species, inhibiting endogenous antioxidant defense enzymes and the brain tissue damage. Tartrazine is an artificial azo dye commonly used in human food and pharmaceutical products. Since the last assessment carried out by the Joint FAO/WHO Expert Committee on Food Additives in 1964, many new studies have been conducted. However, there is a little information about the effects on learning and memory performance. The present study was conducted to evaluate the toxic effect of tartrazine on the learning and memory functions in animals and its possible mechanism involved. Based on our results, we believe that more extensive assessment of food additives in current use is warranted. © 2011 Institute of Food

Online unsupervised formation of cell assemblies for the encoding of multiple cognitive maps.

Science.gov (United States)

Salihoglu, Utku; Bersini, Hugues; Yamaguchi, Yoko; Molter, Colin

2009-01-01

Since their introduction sixty years ago, cell assemblies have proved to be a powerful paradigm for brain information processing. After their introduction in artificial intelligence, cell assemblies became commonly used in computational neuroscience as a neural substrate for content addressable memories. However, the mechanisms underlying their formation are poorly understood and, so far, there is no biologically plausible algorithms which can explain how external stimuli can be online stored in cell assemblies. We addressed this question in a previous paper [Salihoglu, U., Bersini, H., Yamaguchi, Y., Molter, C., (2009). A model for the cognitive map formation: Application of the retroaxonal theory. In Proc. IEEE international joint conference on neural networks], were, based on biologically plausible mechanisms, a novel unsupervised algorithm for online cell assemblies' creation was developed. The procedure involved simultaneously, a fast Hebbian/anti-Hebbian learning of the network's recurrent connections for the creation of new cell assemblies, and a slower feedback signal which stabilized the cell assemblies by learning the feedforward input connections. Here, we first quantify the role played by the retroaxonal feedback mechanism. Then, we show how multiple cognitive maps, composed by a set of orthogonal input stimuli, can be encoded in the network. As a result, when facing a previously learned input, the system is able to retrieve the cognitive map it belongs to. As a consequence, ambiguous inputs which could belong to multiple cognitive maps can be disambiguated by the knowledge of the context, i.e. the cognitive map.

Universal core model for multiple-gate field-effect transistors with short channel and quantum mechanical effects

Science.gov (United States)

Shin, Yong Hyeon; Bae, Min Soo; Park, Chuntaek; Park, Joung Won; Park, Hyunwoo; Lee, Yong Ju; Yun, Ilgu

2018-06-01

A universal core model for multiple-gate (MG) field-effect transistors (FETs) with short channel effects (SCEs) and quantum mechanical effects (QMEs) is proposed. By using a Young’s approximation based solution for one-dimensional Poisson’s equations the total inversion charge density (Q inv ) in the channel is modeled for double-gate (DG) and surrounding-gate SG (SG) FETs, following which a universal charge model is derived based on the similarity of the solutions, including for quadruple-gate (QG) FETs. For triple-gate (TG) FETs, the average of DG and QG FETs are used. A SCEs model is also proposed considering the potential difference between the channel’s surface and center. Finally, a QMEs model for MG FETs is developed using the quantum correction compact model. The proposed universal core model is validated on commercially available three-dimensional ATLAS numerical simulations.

Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

Science.gov (United States)

Santollo, Jessica; Daniels, Derek

2015-12-01

Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood. An obvious step toward addressing this open question is identifying which estrogen receptor subtypes are involved and what intracellular processes are involved. This question, however, is complicated not only by the variety of estrogen receptor subtypes that exist, but also because many subtypes have multiple locations of action (i.e. in the nucleus or in the plasma membrane). This review will highlight our current understanding of the roles that specific estrogen receptor subtypes play in mediating estradiol's anorexigenic and anti-dipsogenic effects along with highlighting the many open questions that remain. This review will also describe recent work being performed by our laboratory aimed at answering these open questions. Copyright © 2015 Elsevier Inc. All rights reserved.

Gouty involvement of the patella and extensor mechanism of the knee mimicking aggressive neoplasm. A case series.

Science.gov (United States)

Kester, Christopher; Wallace, Matthew T; Jelinek, James; Aboulafia, Albert

2018-06-01

Gout is a common inflammatory crystal deposition disease that occurs in many joints throughout the body. Active gout is most often associated with painful synovitis causing searing joint pains, but gout can also produce large masses of space-occupying deposits called tophi. Tophi are most frequently seen in juxta-articular locations with or without bony erosion and are often misdiagnosed as degenerative joint disease. Soft tissue deposits and tendon involvement are also known manifestations of gout, but can present with indeterminate and alarming findings on imaging. We present three cases of tophaceous gout mimicking aggressive neoplasms in the extensor mechanism of the knee. All cases presented as extensor tendon masses eroding into the patella, with imaging findings initially concerning for primary musculoskeletal malignancy.

Transcriptional Regulation of Brain-Derived Neurotrophic Factor (BDNF) by Methyl CpG Binding Protein 2 (MeCP2): a Novel Mechanism for Re-Myelination and/or Myelin Repair Involved in the Treatment of Multiple Sclerosis (MS).

Science.gov (United States)

KhorshidAhmad, Tina; Acosta, Crystal; Cortes, Claudia; Lakowski, Ted M; Gangadaran, Surendiran; Namaka, Michael

2016-03-01

Multiple sclerosis (MS) is a chronic progressive, neurological disease characterized by the targeted immune system-mediated destruction of central nervous system (CNS) myelin. Autoreactive CD4+ T helper cells have a key role in orchestrating MS-induced myelin damage. Once activated, circulating Th1-cells secrete a variety of inflammatory cytokines that foster the breakdown of blood-brain barrier (BBB) eventually infiltrating into the CNS. Inside the CNS, they become reactivated upon exposure to the myelin structural proteins and continue to produce inflammatory cytokines such as tumor necrosis factor α (TNFα) that leads to direct activation of antibodies and macrophages that are involved in the phagocytosis of myelin. Proliferating oligodendrocyte precursors (OPs) migrating to the lesion sites are capable of acute remyelination but unable to completely repair or restore the immune system-mediated myelin damage. This results in various permanent clinical neurological disabilities such as cognitive dysfunction, fatigue, bowel/bladder abnormalities, and neuropathic pain. At present, there is no cure for MS. Recent remyelination and/or myelin repair strategies have focused on the role of the neurotrophin brain-derived neurotrophic factor (BDNF) and its upstream transcriptional repressor methyl CpG binding protein (MeCP2). Research in the field of epigenetic therapeutics involving histone deacetylase (HDAC) inhibitors and lysine acetyl transferase (KAT) inhibitors is being explored to repress the detrimental effects of MeCP2. This review will address the role of MeCP2 and BDNF in remyelination and/or myelin repair and the potential of HDAC and KAT inhibitors as novel therapeutic interventions for MS.

One-dimensional multiple-well oscillators: A time-dependent

Indian Academy of Sciences (India)

... quantum mechanical multiple-well oscillators. An imaginary-time evolution technique, coupled with the minimization of energy expectation value to reach a global minimum, subject to orthogonality constraint (for excited states) has been employed. Pseudodegeneracy in symmetric, deep multiple-well potentials, probability ...

The progestin etonogestrel enhances the respiratory response to metabolic acidosis in newborn rats. Evidence for a mechanism involving supramedullary structures.

Science.gov (United States)

Loiseau, Camille; Osinski, Diane; Joubert, Fanny; Straus, Christian; Similowski, Thomas; Bodineau, Laurence

2014-05-01

Central congenital hypoventilation syndrome is a neuro-respiratory disease characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+) chemosensitivity has been observed in some central congenital hypoventilation syndrome patients coincidental with contraceptive treatment by a potent progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin effect remain unknown, although structures of medulla oblongata, midbrain or diencephalon are known to be targets for progesterone. In the present study, on ex vivo preparations of central nervous system of newborn rats, we show that acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the increased respiratory frequency induced by metabolic acidosis via a mechanism involving supramedullary structures located in pontine, mesencephalic or diencephalic regions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cerebral arterial gas embolism from attempted mechanical thrombectomy: recovery following hyperbaric oxygen therapy.

Science.gov (United States)

Segan, Louise; Permezel, Fiona; Ch'ng, Wei; Millar, Ian; Brooks, Mark; Lee-Archer, Matt; Cloud, Geoffrey

2018-04-01

Cerebral arterial gas embolism is a recognised complication of endovascular intervention with an estimated incidence of 0.08%. Its diagnosis is predominantly clinical, supported by neuroimaging. The treatment relies on alleviating mechanical obstruction and reversing the proinflammatory processes that contribute to tissue ischaemia. Hyperbaric oxygen therapy is an effective treatment and has multiple mechanisms to reverse the pathological processes involved in cerebral arterial gas embolism. Symptomatic cerebral arterial gas embolism is a rare complication of endovascular intervention for acute ischaemic stroke. Although there are no previous descriptions of its successful treatment with hyperbaric oxygen therapy following mechanical thrombectomy, this is likely to become more common as mechanical thrombectomy is increasingly used worldwide to treat acute ischaemic stroke. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Differences in mechanisms of failure, intraoperative findings, and surgical characteristics between single- and multiple-revision ACL reconstructions: a MARS cohort study.

Science.gov (United States)

Chen, James L; Allen, Christina R; Stephens, Thomas E; Haas, Amanda K; Huston, Laura J; Wright, Rick W; Feeley, Brian T

2013-07-01

The factors that lead to patients failing multiple anterior cruciate ligament (ACL) reconstructions are not well understood. Multiple-revision ACL reconstruction will have different characteristics than first-time revision in terms of previous and current graft selection, mode of failure, chondral/meniscal injuries, and surgical charactieristics. Case-control study; Level of evidence, 3. A prospective multicenter ACL revision database was utilized for the time period from March 2006 to June 2011. Patients were divided into those who underwent a single-revision ACL reconstruction and those who underwent multiple-revision ACL reconstructions. The primary outcome variable was Marx activity level. Primary data analyses between the groups included a comparison of graft type, perceived mechanism of failure, associated injury (meniscus, ligament, and cartilage), reconstruction type, and tunnel position. Data were compared by analysis of variance with a post hoc Tukey test. A total of 1200 patients (58% men; median age, 26 years) were enrolled, with 1049 (87%) patients having a primary revision and 151 (13%) patients having a second or subsequent revision. Marx activity levels were significantly higher (9.77) in the primary-revision group than in those patients with multiple revisions (6.74). The most common cause of reruptures was a traumatic, noncontact ACL graft injury in 55% of primary-revision patients; 25% of patients had a nontraumatic, gradual-onset recurrent injury, and 11% had a traumatic, contact injury. In the multiple-revision group, a nontraumatic, gradual-onset injury was the most common cause of recurrence (47%), followed by traumatic noncontact (35%) and nontraumatic sudden onset (11%) (P < .01 between groups). Chondral injuries in the medial compartment were significantly more common in the multiple-revision group than in the single-revision group, as were chondral injuries in the patellofemoral compartment. Patients with multiple-revision ACL

Deciphering the mechanisms involved in Portulaca oleracea (C4) response to drought: metabolic changes including crassulacean acid-like metabolism induction and reversal upon re-watering.

Science.gov (United States)

D'Andrea, Rodrigo Matías; Andreo, Carlos Santiago; Lara, María Valeria

2014-11-01

Portulaca oleracea is a C(4) plant; however, under drought it can change its carbon fixation metabolism into a crassulacean acid metabolism (CAM)-like one. While the C(3) -CAM shift is well known, the C(4) -CAM transition has only been described in Portulaca. Here, a CAM-like metabolism was induced in P. oleracea by drought and then reversed by re-watering. Physiological and biochemical approaches were undertaken to evaluate the drought and recovery responses. In CAM-like plants, chlorophyll fluorescence parameters were transitory affected and non-radiative energy dissipation mechanisms were induced. Induction of flavonoids, betalains and antioxidant machinery may be involved in photosynthetic machinery protection. Metabolic analysis highlights a clear metabolic shift, when a CAM-like metabolism is induced and then reversed. Increases in nitrogenous compounds like free amino acids and urea, and of pinitol could contribute to withstand drought. Reciprocal variations in arginase and urease in drought-stressed and in re-watered plants suggest urea synthesis is strictly regulated. Recovery of C(4) metabolism was accounted by CO(2) assimilation pattern and malate levels. Increases in glycerol and in polyamines would be of importance of re-watered plants. Collectively, in P. oleracea multiple strategies, from induction of several metabolites to the transitory development of a CAM-like metabolism, participate to enhance its adaptation to drought. © 2014 Scandinavian Plant Physiology Society.

Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

Directory of Open Access Journals (Sweden)

Bassam R Ali

Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

Effects of mathematics computer games on special education students’ multiplicative reasoning ability

NARCIS (Netherlands)

Bakker, M.|info:eu-repo/dai/nl/355337770; Van den Heuvel-Panhuizen, M.|info:eu-repo/dai/nl/069266255; Robitzsch, Alexander

2016-01-01

This study examined the effects of a teacher-delivered intervention with online math-ematics mini-games on special education students’ multiplicative reasoning ability(multiplication and division). The games involved declarative, procedural, as well asconceptual knowledge of multiplicative

Effects of mathematics computer games on special education students' multiplicative reasoning ability

NARCIS (Netherlands)

Bakker, M.; Heuvel-Panhuizen, M.H.A.M. van den; Robitzsch, A.

2016-01-01

This study examined the effects of a teacher-delivered intervention with online mathematics mini-games on special education students' multiplicative reasoning ability (multiplication and division). The games involved declarative, procedural, as well as conceptual knowledge of multiplicative

Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

Science.gov (United States)

Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

2018-02-01

To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p 40). The volume of right middle frontal gyrus reduced significantly (p right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

Sympathetic β-adrenergic mechanism in pudendal inhibition of nociceptive and non-nociceptive reflex bladder activity.

Science.gov (United States)

Kadow, Brian T; Lyon, Timothy D; Zhang, Zhaocun; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

2016-07-01

This study investigated the role of the hypogastric nerve and β-adrenergic mechanisms in the inhibition of nociceptive and non-nociceptive reflex bladder activity induced by pudendal nerve stimulation (PNS). In α-chloralose-anesthetized cats, non-nociceptive reflex bladder activity was induced by slowly infusing saline into the bladder, whereas nociceptive reflex bladder activity was induced by replacing saline with 0.25% acetic acid (AA) to irritate the bladder. PNS was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. During saline infusion, PNS at 2T and 4T significantly (P reflex bladder activity. In addition to this peripheral mechanism, a central nervous system mechanism involving metabotropic glutamate 5 receptors also has a role in PNS inhibition. Copyright © 2016 the American Physiological Society.

Verifiably Truthful Mechanisms

DEFF Research Database (Denmark)

Branzei, Simina; Procaccia, Ariel D.

2015-01-01

the computational sense). Our approach involves three steps: (i) specifying the structure of mechanisms, (ii) constructing a verification algorithm, and (iii) measuring the quality of verifiably truthful mechanisms. We demonstrate this approach using a case study: approximate mechanism design without money...

Multiple electromechanically-induced-transparency windows and Fano resonances in hybrid nano-electro-optomechanics

Science.gov (United States)

Ullah, Kamran; Jing, Hui; Saif, Farhan

2018-03-01

We show multiple electromechanically-induced transparency (EMIT) windows in a hybrid nano-electro-optomechanical system in the presence of two-level atoms coupled to a single-mode cavity field. The multiple EMIT-window profile can be observed by controlling the atom field coupling as well as Coulomb coupling between the two charged mechanical resonators. We derive the analytical expression of the multiple-EMIT-windows profile and describe the splitting of multiple EMIT windows as a function of optomechanical coupling, atom-field coupling, and Coulomb coupling. In particular, we discuss the robustness of the system against the cavity decay rate. We compare the results of identical mechanical resonators to different mechanical resonators. We further show how the hybrid nano-electro-optomechanics coupled system can lead to the splitting of the multiple Fano resonances (MFR). The Fano resonances are very sensitive to decay terms in such systems, i.e., atoms, cavities, and the mechanical resonators.

Glucan: mechanisms involved in its radioprotective effect

International Nuclear Information System (INIS)

Patchen, M.L.; D'Alesandro, M.M.; Brook, I.; Blakely, W.F.; MacVittie, T.J.

1987-01-01

It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested

Lipid and protein composition as driving force for multiple sclerosis

Science.gov (United States)

Beck, Roy; Shaharabani, Rona

Physical models and experiments often reduce the number of components aiming to address the fundamental mechanisms. Nevertheless, the inherent heterogeneity is an essential ingredient in the biological context. We present our recent efforts to model and understand the development of multiple sclerosis (MS) from a biophysical perspective. Myelin sheath is a multilamellar complex of various lipids and proteins that surround axons and acts as an insulating layer for proper nerve conduction. In MS the myelin structure is disrupted impairing its function. Previous studies showed that MS is correlated with small lipid composition variation and reduction in the adhesive myelin basic protein. We found that such alterations result in pathological phase transition from a lamellar to inverted hexagonal that involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. Since the etiology and recovery pathways of MS are currently unclear, these findings delineate novel functional roles to dominant constituents in cytoplasmic myelin sheaths, shed new light on mechanisms disrupting lipid-protein complexes, and suggest new courses for diagnosis and treatment for MS.

Drug involvement in fatal overdoses

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Christopher J. Ruhm

2017-12-01

Full Text Available Death certificate data from the Multiple Cause of Death (MCOD files were analyzed to better understand the drug categories most responsible for the increase in fatal overdoses occurring between 1999 and 2014. Statistical adjustment methods were used to account for the understatement in reported drug involvement occurring because death certificates frequently do not specify which drugs were involved in the deaths. The frequency of combination drug use introduced additional uncertainty and so a distinction was made between any versus exclusive drug involvement. Many results were sensitive to the starting and ending years chosen for examination. Opioid analgesics played a major role in the increased drug deaths for analysis windows starting in 1999 but other drugs, particularly heroin, became more significant for recent time periods. Combination drug use was important for all time periods and needs to be accounted for when designing policies to slow or reverse the increase in overdose deaths.

Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury.

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Kawai, Chihiro; Kotani, Hirokazu; Miyao, Masashi; Ishida, Tokiko; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-04-01

Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Multiple photon resonances

International Nuclear Information System (INIS)

Elliott, C.J.; Feldman, B.J.

1979-02-01

A detailed theoretical analysis is presented of the interaction of intense near-resonant monochromatic radiation with an N-level anharmonic oscillator. In particular, the phenomenon of multiple photon resonance, the process by which an N-level system resonantly absorbs two or more photons simultaneously, is investigated. Starting from the Schroedinger equation, diagrammatic techniques are developed that allow the resonant process to be analyzed quantitatively, in analogy with well-known two-level coherent phenomena. In addition, multiple photon Stark shifts of the resonances, shifts absent in two-level theory, are obtained from the diagrams. Insights into the nature of multiple photon resonances are gained by comparing the quantum mechanical system with classical coupled pendulums whose equations of motion possess identical eigenvalues and eigenvectors. In certain limiting cases, including that of the resonantly excited N-level harmonic oscillator and that of the equally spaced N-level system with equal matrix elements, analytic results are derived. The influence of population relaxation and phase-disrupting collisions on the multiple photon process are also analyzed, the latter by extension of the diagrammatic technique to the density matrix equations of motion. 11 figures

Single turnover studies of oxidative halophenol dehalogenation by horseradish peroxidase reveal a mechanism involving two consecutive one electron steps: toward a functional halophenol bioremediation catalyst.

Science.gov (United States)

Sumithran, Suganya; Sono, Masanori; Raner, Gregory M; Dawson, John H

2012-12-01

Horseradish peroxidase (HRP) catalyzes the oxidative para-dechlorination of the environmental pollutant/carcinogen 2,4,6-trichlorophenol (2,4,6-TCP). A possible mechanism for this reaction is a direct oxygen atom transfer from HRP compound I (HRP I) to trichlorophenol to generate 2,6-dichloro 1,4-benzoquinone, a two-electron transfer process. An alternative mechanism involves two consecutive one-electron transfer steps in which HRP I is reduced to compound II (HRP II) and then to the ferric enzyme as first proposed by Wiese et al. [F.W. Wiese, H.C. Chang, R.V. Lloyd, J.P. Freeman, V.M. Samokyszyn, Arch. Environ. Contam. Toxicol. 34 (1998) 217-222]. To probe the mechanism of oxidative halophenol dehalogenation, the reactions between 2,4,6-TCP and HRP compounds I or II have been investigated under single turnover conditions (i.e., without excess H(2)O(2)) using rapid scan stopped-flow spectroscopy. Addition of 2,4,6-TCP to HRP I leads rapidly to HRP II and then more slowly to the ferric resting state, consistent with a mechanism involving two consecutive one-electron oxidations of the substrate via a phenoxy radical intermediate. HRP II can also directly dechlorinate 2,4,6-TCP as judged by rapid scan stopped-flow and mass spectrometry. This observation is particularly significant since HRP II can only carry out one-electron oxidations. A more detailed understanding of the mechanism of oxidative halophenol dehalogenation will facilitate the use of HRP as a halophenol bioremediation catalyst. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism

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Xinmiao Yan

2016-03-01

Full Text Available Pyrrolizidine Alkaloids (PAs are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1 and glutathione peroxidase 1 (GPX1 targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Identification of Toxic Pyrrolizidine Alkaloids and Their Common Hepatotoxicity Mechanism.

Science.gov (United States)

Yan, Xinmiao; Kang, Hong; Feng, Jun; Yang, Yiyan; Tang, Kailin; Zhu, Ruixin; Yang, Li; Wang, Zhengtao; Cao, Zhiwei

2016-03-07

Pyrrolizidine Alkaloids (PAs) are currently one of the most important botanical hepatotoxic ingredients. Glutathion (GSH) metabolism is the most reported pathway involved in hepatotoxicity mechanism of PAs. We speculate that, for different PAs, there should be a common mechanism underlying their hepatotoxicity in GSH metabolism. Computational methods were adopted to test our hypothesis in consideration of the limitations of current experimental approaches. Firstly, the potential targets of 22 PAs (from three major PA types) in GSH metabolism were identified by reverse docking; Secondly, glutathione S-transferase A1 (GSTA1) and glutathione peroxidase 1 (GPX1) targets pattern was found to be a special characteristic of toxic PAs with stepwise multiple linear regressions; Furthermore, the molecular mechanism underlying the interactions within toxic PAs and these two targets was demonstrated with the ligand-protein interaction analysis; Finally, GSTA1 and GPX1 were proved to be significant nodes in GSH metabolism. Overall, toxic PAs could be identified by GSTA1 and GPX1 targets pattern, which suggests their common hepatotoxicity mechanism: the interfering of detoxication in GSH metabolism. In addition, all the strategies developed here could be extended to studies on toxicity mechanism of other toxins.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

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David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

Science.gov (United States)

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Mecanismos envolvidos na cicatrização: uma revisão Mechanisms involved in wound healing: a revision

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Carlos Aberto Balbino

2005-03-01

Full Text Available Os mecanismos envolvidos no processo de reparo de tecidos estão revisados nesse trabalho. O processo de cicatrização ocorre fundamentalmente em três fases: inflamação, formação de tecido de granulação e deposição de matriz extracelular e remodelação. Os eventos celulares e tissulares de cada uma dessas fases estão descritos e discutidos. Os mediadores químicos estão correlacionados com os eventos do processo de cicatrização e as células envolvidas. Especial ênfase é dada à participação dos fatores de crescimento.The mechanisms involved in tissue repair are revised. The wound healing process occurs basically in three phases: inflammation, formation of granulating tissue and extracellular tissue deposition, and tissue remodeling. The cellular and tissue events of each phase are described and discussed. The chemical mediators and their interplay with the wound healing events and cells involved are also discussed. However, especial attention was given to the role played by the growth factors in the tissue repair process.

Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

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Shengzhang Lin

2013-01-01

Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

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Thomas Vorup-Jensen

2012-11-01

Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

Multiple parton interactions at the LHC

CERN Document Server

Gaunt, Jonathan Richard

2018-01-01

Many high-energy collider experiments (including the current Large Hadron Collider at CERN) involve the collision of hadrons. Hadrons are composite particles consisting of partons (quarks and gluons), and this means that in any hadron–hadron collision there will typically be multiple collisions of the constituents — i.e. multiple parton interactions (MPI). Understanding the nature of the MPI is important in terms of searching for new physics in the products of the scatters, and also in its own right to gain a greater understanding of hadron structure. This book aims at providing a pedagogical introduction and a comprehensive review of different research lines linked by an involvement of MPI phenomena. It is written by pioneers as well as young leading scientists, and reviews both experimental findings and theoretical developments, discussing also the remaining open issues.

MULTIPLE PROJECT MANAGEMENT IN THE CONSTRUCTION INDSUTRY

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Luciana Hazin Alencar

2010-06-01

Full Text Available The field of project management has historically focused on the administration of one project at a time, a focus that is insufficient given the growing need for organizations to manage multiple projects simultaneously. The requirements of Multiple Project Management (MPM involves demands and practices that are different from those of single projects. MPM poses a special need for coordination of shared resources across multiple projects in a way that can maintain the firm’s strategic focus and facilitate effective decision making. The construction industry is noteworthy for its frequent need for the management of multiple projects. This paper offers a review of the last five years of indexed literature related to multiple project management in the construction industry, identifies gaps and suggests promising new avenues of inquiry.

Nanocrystalline cellulose-dispersed AKD emulsion for enhancing the mechanical and multiple barrier properties of surface-sized paper.

Science.gov (United States)

Yang, Luming; Lu, Sheng; Li, Juanjuan; Zhang, Fengshan; Cha, Ruitao

2016-01-20

In this study, we employed nanocrystalline cellulose (NCC) as an efficient dispersant to perpare alkyl ketene dimer (AKD) emulsion. The particle size and zeta potential of AKD/NCC emulsion were measured, which were approximately 5 μm and -50 mV, respectively. The surface-sized paper possessed multiple barriers properties. The air permeability of surface-sized paper was 0.29 μm/Pas and the sizing degree reached 42 s when the amount of sizing was 12.58 g/m(2) with a 96.83% decrease and a 40.00%, increase, respectively. Furthermore, the mechanical properties were optimal when the amount of sizing was about 8 g/m(2). AKD/NCC emulsion acted as a good reinforcing agent in surface-sized paper. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antitumor Mechanisms of Curcumae Rhizoma Based on Network Pharmacology

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Yan-Hua Bi

2018-01-01

Full Text Available Curcumae Rhizoma, a traditional Chinese medication, is commonly used in both traditional treatment and modern clinical care. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Curcumae Rhizoma using a drug-likeness approach. Candidate protein targets with functions related to cancer were predicted by reverse docking and then checked by manual search of the PubMed database. Potential target genes were uploaded to the GeneMANIA server and DAVID 6.8 database for analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results revealed that the anticancer activity of Curcumae Rhizoma potentially involves 13 active compounds, 33 potential targets, and 31 signaling pathways, thus constituting a “multiple compounds, multiple targets, and multiple pathways” network corresponding to the concept of systematic actions in TCM. These findings provide an overview of the anticancer action of Curcumae Rhizoma from a network perspective, as well as setting an example for future studies of other materials used in TCM.

Molecular Mechanisms of Mouse Skin Tumor Promotion

International Nuclear Information System (INIS)

Rundhaug, Joyce E.; Fischer, Susan M.

2010-01-01

Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation, or due to a block in terminal differentiation or resistance to apoptosis is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-α and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion

Mechanisms and secondary factors involved in the induction of radiation transformation in vitro

International Nuclear Information System (INIS)

Little, J.B.

1983-01-01

The long term of this research program was to gain information concerning the mechanisms that determine the carcinogenic effects of ionizing radiation, particularly high LET radiation exposure. The experimental approach involves parallel studies of the induction of malignant transformation in BALB/3T3 cells and of specific gene mutations in human lymphoblastoid cells. Emphasis was on the biologic effects of internally incorporated Auger electron emitting radionuclides and the initiation of studies to determine the effects of low dose-rate neutron exposure. Auger electron irradiation sever as a model for high LET-type radiation effects and as an experimental tool for studying the effects of radiation at specific sites within the cell. Auger-emitting radiosotopes are commonly used in clinical nuclear medicine, rendering them a potential hazard to human populations. We examined the influence of cellular localization of Auger-emitting radionuclides and the spectrum of energy distribution in DNA on their mutagenic, cytogenetic, and transformational effects. The effects of 125 I (an energetic beta emitter) were compared. We studied the induction of cytogenetic changes by 125 I exposure of the cell membrane, as well as its potential to promote (enhance) transformation initiated by low dose external x-ray exposure. We will investigate the Relative Biological Effectiveness for mutagenesis and transformation of low doses of fast neutrons delivered continuously at variable low dose-rates. 34 refs., 1 tab

Talker-specific learning in amnesia: Insight into mechanisms of adaptive speech perception.

Science.gov (United States)

Trude, Alison M; Duff, Melissa C; Brown-Schmidt, Sarah

2014-05-01

A hallmark of human speech perception is the ability to comprehend speech quickly and effortlessly despite enormous variability across talkers. However, current theories of speech perception do not make specific claims about the memory mechanisms involved in this process. To examine whether declarative memory is necessary for talker-specific learning, we tested the ability of amnesic patients with severe declarative memory deficits to learn and distinguish the accents of two unfamiliar talkers by monitoring their eye-gaze as they followed spoken instructions. Analyses of the time-course of eye fixations showed that amnesic patients rapidly learned to distinguish these accents and tailored perceptual processes to the voice of each talker. These results demonstrate that declarative memory is not necessary for this ability and points to the involvement of non-declarative memory mechanisms. These results are consistent with findings that other social and accommodative behaviors are preserved in amnesia and contribute to our understanding of the interactions of multiple memory systems in the use and understanding of spoken language. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cystic angiomatosis with splenic involvement: unusual MRI findings

Energy Technology Data Exchange (ETDEWEB)

Vanhoenacker, F.M. [Dept. of Radiology, Univ. Hospital Antwerp, Edegem (Belgium); Dept. of Radiology, AZ St-Maarten, Campus Duffel, Duffel (Belgium); Schepper, A.M. [Dept. of Radiology, Univ. Hospital Antwerp, Edegem (Belgium); Raeve, H. [Dept. of Pathology, Univ. Hospital Antwerp, Edegem (Belgium); Berneman, Z. [Dept. of Hematology, Univ. Hospital Antwerp, Edegem (Belgium)

2003-12-01

Cystic angiomatosis is a rare disorder with a poor prognosis. We describe a case of a 33-year-old woman who presented with longstanding bone pain, hemolytic anemia, and an enlarged spleen. Radiologically, multiple osseous lesions with a mixed pattern of lytic and sclerotic areas were seen within the shoulders, spine, and pelvis. On CT and MRI of the abdomen, the spleen was markedly enlarged, with internal hyperdense foci on non-contrast CT scan, corresponding to low signal intensity areas on all MR pulse sequences. After administration of contrast, a mottled enhancement pattern throughout the entire spleen was seen both on CT and MRI. Cystic angiomatosis was proven by histological analysis of a biopsy specimen of an involved vertebra and histopathological examination of the spleen after subsequent splenectomy. This is the first report of a patient with disseminated cystic angiomatosis with splenic involvement in which the MRI features differ from the previous reports. Instead of the usual pattern consisting of multiple well-defined cystic lesions, a diffuse involvement replacing the entire spleen, with heterogeneous signal intensities on T2-weighted images and heterogeneous enhancement pattern, was seen in our patient. (orig.)

Cystic angiomatosis with splenic involvement: unusual MRI findings

International Nuclear Information System (INIS)

Vanhoenacker, F.M.; Schepper, A.M.; Raeve, H.; Berneman, Z.

2003-01-01

Cystic angiomatosis is a rare disorder with a poor prognosis. We describe a case of a 33-year-old woman who presented with longstanding bone pain, hemolytic anemia, and an enlarged spleen. Radiologically, multiple osseous lesions with a mixed pattern of lytic and sclerotic areas were seen within the shoulders, spine, and pelvis. On CT and MRI of the abdomen, the spleen was markedly enlarged, with internal hyperdense foci on non-contrast CT scan, corresponding to low signal intensity areas on all MR pulse sequences. After administration of contrast, a mottled enhancement pattern throughout the entire spleen was seen both on CT and MRI. Cystic angiomatosis was proven by histological analysis of a biopsy specimen of an involved vertebra and histopathological examination of the spleen after subsequent splenectomy. This is the first report of a patient with disseminated cystic angiomatosis with splenic involvement in which the MRI features differ from the previous reports. Instead of the usual pattern consisting of multiple well-defined cystic lesions, a diffuse involvement replacing the entire spleen, with heterogeneous signal intensities on T2-weighted images and heterogeneous enhancement pattern, was seen in our patient. (orig.)

Priming by Rhizobacterium Protects Tomato Plants from Biotrophic and Necrotrophic Pathogen Infections through Multiple Defense Mechanisms

Science.gov (United States)

Ahn, Il-Pyung; Lee, Sang-Woo; Kim, Min Gab; Park, Sang-Ryeol; Hwang, Duk-Ju; Bae, Shin-Chul

2011-01-01

A selected strain of rhizobacterium, Pseudomonas putida strain LSW17S (LSW17S), protects tomato plants (Lycopersicon esculentum L. cv. Seokwang) from bacterial speck by biotrophic Pseudomonas syringae pv. tomato strain DC3000 (DC3000) and bacterial wilt by necrotrophic Ralstonia solanacearum KACC 10703 (Rs10703). To investigate defense mechanisms induced by LSW17S in tomato plants, transcription patterns of pathogenesis-related (PR) genes and H2O2 production were analyzed in plants treated with LSW17S and subsequent pathogen inoculation. LSW17S alone did not induce transcriptions of employed PR genes in leaves and roots. DC3000 challenge following LSW17S triggered rapid transcriptions of PR genes and H2O2 production in leaves and roots. Catalase infiltration with DC3000 attenuated defense-related responses and resistance against DC3000 infection. Despite depriving H2O2 production and PR1b transcription by the same treatment, resistance against Rs10703 infection was not deterred significantly. H2O2 is indispensable for defense signaling and/or mechanisms primed by LSW17S and inhibition of bacterial speck, however, it is not involved in resistance against bacterial wilt. PMID:21710203

Effect of multiple scattering on lidar measurements

International Nuclear Information System (INIS)

Cohen, A.

1977-01-01

The lidar equation in its standard form involves the assumption that the scattered irradiance reaching the lidar receiver has been only singly scattered. However, in the cases of scattering from clouds and thick aerosol layers, it is shown that multiple scattering cannot be neglected. An experimental method for the detection of multiple scattering by depolarization measurement techniques is discussed. One method of theoretical calculations of double-scattering is presented and discussed

Multiple-event probability in general-relativistic quantum mechanics

International Nuclear Information System (INIS)

Hellmann, Frank; Mondragon, Mauricio; Perez, Alejandro; Rovelli, Carlo

2007-01-01

We discuss the definition of quantum probability in the context of 'timeless' general-relativistic quantum mechanics. In particular, we study the probability of sequences of events, or multievent probability. In conventional quantum mechanics this can be obtained by means of the 'wave function collapse' algorithm. We first point out certain difficulties of some natural definitions of multievent probability, including the conditional probability widely considered in the literature. We then observe that multievent probability can be reduced to single-event probability, by taking into account the quantum nature of the measuring apparatus. In fact, by exploiting the von-Neumann freedom of moving the quantum/classical boundary, one can always trade a sequence of noncommuting quantum measurements at different times, with an ensemble of simultaneous commuting measurements on the joint system+apparatus system. This observation permits a formulation of quantum theory based only on single-event probability, where the results of the wave function collapse algorithm can nevertheless be recovered. The discussion also bears on the nature of the quantum collapse

Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions.

Science.gov (United States)

Kravchenko, Julia; Corsini, Emanuela; Williams, Marc A; Decker, William; Manjili, Masoud H; Otsuki, Takemi; Singh, Neetu; Al-Mulla, Faha; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H; Lowe, Leroy; Lyerly, H Kim

2015-06-01

An increasing number of studies suggest an important role of host immunity as a barrier to tumor formation and progression. Complex mechanisms and multiple pathways are involved in evading innate and adaptive immune responses, with a broad spectrum of chemicals displaying the potential to adversely influence immunosurveillance. The evaluation of the cumulative effects of low-dose exposures from the occupational and natural environment, especially if multiple chemicals target the same gene(s) or pathway(s), is a challenge. We reviewed common environmental chemicals and discussed their potential effects on immunosurveillance. Our overarching objective was to review related signaling pathways influencing immune surveillance such as the pathways involving PI3K/Akt, chemokines, TGF-β, FAK, IGF-1, HIF-1α, IL-6, IL-1α, CTLA-4 and PD-1/PDL-1 could individually or collectively impact immunosurveillance. A number of chemicals that are common in the anthropogenic environment such as fungicides (maneb, fluoxastrobin and pyroclostrobin), herbicides (atrazine), insecticides (pyridaben and azamethiphos), the components of personal care products (triclosan and bisphenol A) and diethylhexylphthalate with pathways critical to tumor immunosurveillance. At this time, these chemicals are not recognized as human carcinogens; however, it is known that they these chemicalscan simultaneously persist in the environment and appear to have some potential interfere with the host immune response, therefore potentially contributing to promotion interacting with of immune evasion mechanisms, and promoting subsequent tumor growth and progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bullous Henoch–Schonlein purpura with involvement of face

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Devdeep Mukherjee

2017-01-01

Full Text Available Henoch–Schonlein purpura (HSP with facial involvement with bullous rashes are extremely rare. A 12-year-old boy presented with abdominal pain and features of arthritis. He also had multiple purpuric rashes over his lower limbs. Gradually, he developed bullous rashes which were seen on his legs and hands and progressed to involve the face. He was confirmed to be suffering from HSP from clinical presentation and skin biopsy. The child responded well to oral steroids. Bullous lesions may be seen in HSP. However, there is neither prognostic significance of this nor does it alter the management. Other causes of bullous lesions should be ruled out. As facial involvement is associated with renal and gastrointestinal involvement, these children should be monitored for sequelae.

Sequential and simultaneous multiple explanation

Directory of Open Access Journals (Sweden)

Robert Litchfield

2007-02-01

Full Text Available This paper reports two experiments comparing variants of multiple explanation applied in the early stages of a judgment task (a case involving employee theft where participants are not given a menu of response options. Because prior research has focused on situations where response options are provided to judges, we identify relevant dependent variables that an intervention might affect when such options are not given. We use these variables to build a causal model of intervention that illustrates both the intended effects of multiple explanation and some potentially competing processes that it may trigger. Although multiple explanation clearly conveys some benefits (e.g., willingness to delay action to engage in information search, increased detail, quality and confidence in alternative explanations in the present experiments, we also found evidence that it may initiate or enhance processes that attenuate its advantages (e.g., feelings that one does not need more data if one has multiple good explanations.

Primary multifocal tuberculous osteomyelitis with involvement of the ribs

Energy Technology Data Exchange (ETDEWEB)

Chang, D.S. [New York University School of Medicine, New York, New York (United States); Rafii, M.; McGuinness, G. [Department of Radiology, NYU Medical Center, New York, NY (United States); Jagirdar, J.S. [Department of Pathology, NYU Medical Center, New York, New York (United States)

1998-11-01

Two cases of primary multifocal tuberculous osteomyelitis with involvement of the rib cage are presented. The lungs were normal and the appearance of the skeletal lesions did not suggest tuberculosis. These lesions were predominantly lytic, with minimal soft tissue involvement. Tuberculosis should be high in the differential diagnosis of multiple destructive bone lesions, especially in patients from regions where tuberculosis is endemic. (orig.) With 5 figs., 21 refs.

Quantum Mechanics/Molecular Mechanics Modeling of Drug Metabolism

DEFF Research Database (Denmark)

Lonsdale, Richard; Fort, Rachel M; Rydberg, Patrik

2016-01-01

)-mexiletine in CYP1A2 with hybrid quantum mechanics/molecular mechanics (QM/MM) methods, providing a more detailed and realistic model. Multiple reaction barriers have been calculated at the QM(B3LYP-D)/MM(CHARMM27) level for the direct N-oxidation and H-abstraction/rebound mechanisms. Our calculated barriers......The mechanism of cytochrome P450(CYP)-catalyzed hydroxylation of primary amines is currently unclear and is relevant to drug metabolism; previous small model calculations have suggested two possible mechanisms: direct N-oxidation and H-abstraction/rebound. We have modeled the N-hydroxylation of (R...... indicate that the direct N-oxidation mechanism is preferred and proceeds via the doublet spin state of Compound I. Molecular dynamics simulations indicate that the presence of an ordered water molecule in the active site assists in the binding of mexiletine in the active site...

Mechanisms of buffer therapy resistance.

Science.gov (United States)

Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

2014-04-01

Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Improvement of diagnostic confidence for detection of multiple myeloma involvement of the ribs by a new CT software generating rib unfolded images: Comparison with 5- and 1-mm axial images

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