Sample records for multiple noxious foci

  1. Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer.

    PubMed

    Konstantakos, A K; Siu, I M; Pretlow, T G; Stellato, T A; Pretlow, T P

    1996-09-01

    Aberrant crypt foci are putative preneoplastic lesions found in the colons of carcinogen-treated rodents and at an increased frequency in humans at increased risk for colon cancer. There is a strong association between aberrant crypt foci and colon cancer, including many shared phenotypic and genetic alterations. The aim of this study is to present further evidence of a relationship between aberrant crypt foci and colon cancer in humans. Multiple aberrant crypt foci from a single patient were identified in unembedded colonic mucosa. Histological sections of the aberrant crypt foci and adjacent mucosa were evaluated for dysplasia, proliferative activity, and pigment-laden macrophages that were characterized with histochemical techniques. The first patient with sporadic colon cancer identified with aberrant crypt foci with carcinoma in situ is described. It is interesting that this 99-year-old patient had multiple carcinomas in situ, pseudomelanosis coli, and two metachronous colon cancers. These data lend support to the hypothesis that aberrant crypt foci are precursors of some colon cancers.

  2. Connecting Model Species to Nature: Predator-Induced Long-Term Sensitization in "Aplysia Californica"

    ERIC Educational Resources Information Center

    Mason, Maria J.; Watkins, Amanda J.; Wakabayashi, Jordann; Buechler, Jennifer; Pepino, Christine; Brown, Michelle; Wright, William G.

    2014-01-01

    Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…

  3. Brain mediators of the effects of noxious heat on pain

    PubMed Central

    Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

    2014-01-01

    Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

  4. Brain mediators of the effects of noxious heat on pain.

    PubMed

    Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

    2014-08-01

    Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

    PubMed Central

    Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

    2013-01-01

    Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

  6. 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation.

    PubMed

    Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D; Nakano, Takashi; Shibata, Atsushi

    2017-12-12

    DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G 2 -phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm 3 . These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation.

  7. Refractory Cushing's disease caused by multinodular ACTH-cell hyperplasia.

    PubMed

    McKeever, P E; Koppelman, M C; Metcalf, D; Quindlen, E; Kornblith, P L; Strott, C A; Howard, R; Smith, B H

    1982-09-01

    A patient with pituitary-dependent hypercortisolism, unresponsive to resection of nodules in the anterior lobe, is described. Histochemical stains of the nodules showed multiple, focal, cellular expansions of the fibrovascular stroma. Transitions between normal and expanded adenohypophysial acini were present. Immunoperoxidase stains for ACTH and other pituitary hormones revealed that these multiple foci contained an excess of ACTH-positive cells. Less than 10% of the cells in these foci were negative for ACTH and positive for other hormones. Serial sections showed that these foci of predominantly ACTH-producing acini were not connected. Clinical, morphological, and immunohistochemical data indicated that ACTH-cell hyperplasia caused Crushing's disease in this patient. Pathologic study of individual cases should concentrate on determining whether hyperplasia or adenoma exist at the time of surgical exploration of the pituitary gland, since this determination is important to proper treatment. Tentative criteria to recognize ACTH-cell hyperplasia are: 1. Multiple foci of ACTH laden cells. 2. A minor subpopulation of cells of alternate hormone series. 3. Expansion without destruction of acini in the adenohypophysis.

  8. 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation

    PubMed Central

    Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D.; Nakano, Takashi; Shibata, Atsushi

    2017-01-01

    DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1–2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G2-phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm3. These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation. PMID:29312614

  9. Spatial organization of transcription machinery and its segregation from the replisome in fast-growing bacterial cells

    PubMed Central

    Cagliero, Cedric; Zhou, Yan Ning; Jin, Ding Jun

    2014-01-01

    In a fast-growing Escherichia coli cell, most RNA polymerase (RNAP) is allocated to rRNA synthesis forming transcription foci at clusters of rrn operons or bacterial nucleolus, and each of the several nascent nucleoids contains multiple pairs of replication forks. The composition of transcription foci has not been determined. In addition, how the transcription machinery is three-dimensionally organized to promote cell growth in concord with replication machinery in the nucleoid remains essentially unknown. Here, we determine the spatial and functional landscapes of transcription and replication machineries in fast-growing E. coli cells using super-resolution-structured illumination microscopy. Co-images of RNAP and DNA reveal spatial compartmentation and duplication of the transcription foci at the surface of the bacterial chromosome, encompassing multiple nascent nucleoids. Transcription foci cluster with NusA and NusB, which are the rrn anti-termination system and are associated with nascent rRNAs. However, transcription foci tend to separate from SeqA and SSB foci, which track DNA replication forks and/or the replisomes, demonstrating that transcription machinery and replisome are mostly located in different chromosomal territories to maintain harmony between the two major cellular functions in fast-growing cells. Our study suggests that bacterial chromosomes are spatially and functionally organized, analogous to eukaryotes. PMID:25416798

  10. Motor correlates of models of secondary bilateral synchrony and multiple epileptic foci.

    PubMed

    Jiruska, Premysl; Proks, Jan; Otáhal, Jakub; Mares, Pavel

    2007-10-01

    Bilateral synchronous epileptiform discharges registered in patients with partial epilepsies may be generated by different pathophysiological mechanisms. Differentiation between underlying mechanisms is often crucial for correct diagnosis and adequate treatment in clinical epileptology. The aim of this study was to model in rats two possible mechanisms--secondary bilateral sychrony and interaction between multiple epilepic foci. Furthermore, to describe in detail semiology, laterality and differences in motor phenomena. Secondary bilateral synchrony was modeled by unilateral topical application of bicuculline methiodide (BMI) over the sensorimotor cortex. Bilateral symmetric application of BMI was used as a model of multiple epileptic foci. Electrographic and behavioural phenomena were recorded for 1h following the application of BMI. Electroencephalogram in both groups was characterized by presence of bilateral synchronous discharges. Myoclonic and clonic seizures involving forelimb and head muscles represented the most common motor seizure pattern in both groups. Significant differences were found in the laterality of motor phenomena. Motor seizures in unilateral foci always started in the contralateral limbs whereas symmetrical foci exhibited bilateral independent onset of convulsions. Similar lateralization was observed in interictal motor phenomena (myoclonic jerks). An important influence of posture on epileptic motor phenomena was demonstrated. Active or passive changes in animal posture (verticalization to bipedal posture) caused conversion from unilateral myoclonic jerks or clonic seizures to bilaterally synchronous (generalized) motor phenomena in both groups.

  11. Gamma knife treatment for refractory epilepsy in seizure focus localized by positron emission tomography/CT★

    PubMed Central

    Bai, Xia; Wang, Xuemei; Wang, Hongwei; Zhao, Shigang; Han, Xiaodong; Hao, Linjun; Wang, Xiangcheng

    2012-01-01

    A total of 80 patients with refractory epilepsy were recruited from the Inner Mongolia Medical College Affiliated Hospital. The foci of 60% of the patients could be positioned using a combined positron emission tomography/CT imaging modality. Hyper- and hypometabolism foci were examined as part of this study. Patients who had abnormal metabolism in positron emission tomography/CT imaging were divided into intermittent-phase group and the seizure-phase group. The intermittent-phase group was further divided into a single-focus group and a multiple-foci group according to the number of seizure foci detected by imaging. Following gamma knife treatment, seizure frequency was significantly lower in the intermittent-phase group and the seizure-phase group. Wieser’s classification reached Grade I or II in nearly 40% of patients. Seizure frequency was significantly lower following treatment, but Wieser’s classification score was significantly higher in the seizure-phase group compared with the intermittent-phase group. Seizure frequency was significantly lower following treatment in the single-focus group, but Wieser’s classification score was significantly higher in the single-focus group as compared with the multiple-foci group. PMID:25317147

  12. Pain anticipation: an activation likelihood estimation meta-analysis of brain imaging studies.

    PubMed

    Palermo, Sara; Benedetti, Fabrizio; Costa, Tommaso; Amanzio, Martina

    2015-05-01

    The anticipation of pain has been investigated in a variety of brain imaging studies. Importantly, today there is no clear overall picture of the areas that are involved in different studies and the exact role of these regions in pain expectation remains especially unexploited. To address this issue, we used activation likelihood estimation meta-analysis to analyze pain anticipation in several neuroimaging studies. A total of 19 functional magnetic resonance imaging were included in the analysis to search for the cortical areas involved in pain anticipation in human experimental models. During anticipation, activated foci were found in the dorsolateral prefrontal, midcingulate and anterior insula cortices, medial and inferior frontal gyri, inferior parietal lobule, middle and superior temporal gyrus, thalamus, and caudate. Deactivated foci were found in the anterior cingulate, superior frontal gyrus, parahippocampal gyrus and in the claustrum. The results of the meta-analytic connectivity analysis provide an overall view of the brain responses triggered by the anticipation of a noxious stimulus. Such a highly distributed perceptual set of self-regulation may prime brain regions to process information where emotion, action and perception as well as their related subcategories play a central role. Not only do these findings provide important information on the neural events when anticipating pain, but also they may give a perspective into nocebo responses, whereby negative expectations may lead to pain worsening. © 2014 Wiley Periodicals, Inc.

  13. Digitally switchable multi-focal lens using freeform optics.

    PubMed

    Wang, Xuan; Qin, Yi; Hua, Hong; Lee, Yun-Han; Wu, Shin-Tson

    2018-04-16

    Optical technologies offering electrically tunable optical power have found a broad range of applications, from head-mounted displays for virtual and augmented reality applications to microscopy. In this paper, we present a novel design and prototype of a digitally switchable multi-focal lens (MFL) that offers the capability of rapidly switching the optical power of the system among multiple foci. It consists of a freeform singlet and a customized programmable optical shutter array (POSA). Time-multiplexed multiple foci can be obtained by electrically controlling the POSA to switch the light path through different segments of the freeform singlet rapidly. While this method can be applied to a broad range of imaging and display systems, we experimentally demonstrate a proof-of-concept prototype for a multi-foci imaging system.

  14. Multi-focal multiphoton lithography.

    PubMed

    Ritschdorff, Eric T; Nielson, Rex; Shear, Jason B

    2012-03-07

    Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

  15. Neurophysiological measures of nociceptive brain activity in the newborn infant--the next steps.

    PubMed

    Hartley, Caroline; Slater, Rebeccah

    2014-03-01

    Infants within neonatal intensive care units can receive multiple medically essential painful procedures per day. How they respond to these events, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years, several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint Article, we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. © 2013 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

  16. 78 FR 23952 - Notice of Temporary Closure on Public Lands in Elmore County, ID

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ...-grouse habitat. The closure will help to slow the spread of noxious weeds; allow planted shrub, forb, and... in the burned area to provide multiple age classes of shrubs in the burned area. Accessible areas of...

  17. A Regional Guidebook for Applying the Hydrogeomorphic Approach to Assessing the Functions of Tidal Fringe Wetlands Along the Mississippi and Alabama Gulf Coast

    DTIC Science & Technology

    2007-04-01

    philoxeroides Alligatorweed Alabama Class C noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; Mississippi noxious weed Ipomoea...Invasive Species Alternanthera philoxeroides Phragmites australis Cuscuta spp. Imperata cylindrica ...weed Cuscuta spp. Dodder Alabama Class A noxious weed Imperata cylindrica Cogongrass Alabama Class A noxious weed; MS noxious weed Ipomoea

  18. Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation.

    PubMed

    Choi, J C; Kim, J; Kang, E; Choi, J-H; Park, W Y; Choi, Y-S; Cha, J; Han, C; Park, S K; Kim, M H; Lee, G H; Do, H-J; Jung, S W; Lee, J-M

    2016-01-01

    We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. [Effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water].

    PubMed

    Xiuwen, Yang; Hongchen, Liu; Ke, Li; Zhen, Jin; Gang, Liu

    2014-12-01

    We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water. Six male and female subjects were subjected to whole-brain fMRI during the phasic delivery of non-noxious hot (23 °C) and no- xious cold (4 °C) water intraoral stimulation. A block-design blood oxygenation level-dependent fMRI scan covering the entire brain was also carried out. The activated cortical areas were as follows: left pre-/post-central gyrus, insula/operculum, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), midbrain red nucleus, and thalamus. The activated cortical areas under cold condition were as follows: left occipital lobe, premotor cortex/Brodmann area (BA) 6, right motor language area BA44, lingual gyrus, parietal lobule (BA7, 40), and primary somatosensory cortex S I. Comparisons of the regional cerebral blood flow response magnitude were made among stereotactically concordant brain regions that showed significant responses under the two conditions of this study. Compared with non-noxious warmth, more regions were activated in noxious coldness, and the magnitude of activation in areas produced after non-noxious warm stimulation significantly increased. However, ACC only significantly increased the magnitude of activation under noxious coldness stimulation. Results suggested that a similar network of regions was activated common to the perception of pain and no-pain produced by either non-noxious warmth or noxious coldness stimulation. Non-noxious warmth also activated more brain regions and significantly increased the response magnitude of cerebral-cortex activation compared with noxious coldness. Noxious coldness stimulation further significantly increased the magnitude of activation in ACC areas compared with noxious warmth.

  20. 7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

  1. 7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

  2. 7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. (a) The Administrator may deny an...

  3. High-Throughput Analysis of Stimulus-Evoked Behaviors in Drosophila Larva Reveals Multiple Modality-Specific Escape Strategies

    PubMed Central

    Ohyama, Tomoko; Jovanic, Tihana; Denisov, Gennady; Dang, Tam C.; Hoffmann, Dominik; Kerr, Rex A.; Zlatic, Marta

    2013-01-01

    All organisms react to noxious and mechanical stimuli but we still lack a complete understanding of cellular and molecular mechanisms by which somatosensory information is transformed into appropriate motor outputs. The small number of neurons and excellent genetic tools make Drosophila larva an especially tractable model system in which to address this problem. We developed high throughput assays with which we can simultaneously expose more than 1,000 larvae per man-hour to precisely timed noxious heat, vibration, air current, or optogenetic stimuli. Using this hardware in combination with custom software we characterized larval reactions to somatosensory stimuli in far greater detail than possible previously. Each stimulus evoked a distinctive escape strategy that consisted of multiple actions. The escape strategy was context-dependent. Using our system we confirmed that the nociceptive class IV multidendritic neurons were involved in the reactions to noxious heat. Chordotonal (ch) neurons were necessary for normal modulation of head casting, crawling and hunching, in response to mechanical stimuli. Consistent with this we observed increases in calcium transients in response to vibration in ch neurons. Optogenetic activation of ch neurons was sufficient to evoke head casting and crawling. These studies significantly increase our understanding of the functional roles of larval ch neurons. More generally, our system and the detailed description of wild type reactions to somatosensory stimuli provide a basis for systematic identification of neurons and genes underlying these behaviors. PMID:23977118

  4. 7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

  5. 7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

  6. 7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

  7. 7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

  8. 7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

  9. 7 CFR 360.300 - Notice of restrictions on movement of noxious weeds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Notice of restrictions on movement of noxious weeds... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 Notice of restrictions on movement of noxious weeds. No person may move a Federal noxious weed into or...

  10. 7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

  11. 7 CFR 360.305 - Disposal of noxious weeds when permits are canceled.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Disposal of noxious weeds when permits are canceled... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.305 Disposal of noxious weeds when permits are canceled. When a permit for the movement of a noxious weed is...

  12. Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

    PubMed Central

    Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone

    2018-01-01

    The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681

  13. Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

    PubMed

    Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

    2018-01-01

    The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

  14. 7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

  15. 7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

  16. 7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

  17. 7 CFR 360.303 - Approval of an application for a permit to move a noxious weed; conditions specified in permit.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... noxious weed; conditions specified in permit. 360.303 Section 360.303 Agriculture Regulations of the... NOXIOUS WEED REGULATIONS § 360.303 Approval of an application for a permit to move a noxious weed... noxious weed. If the application is approved, the Administrator will issue the permit including any...

  18. Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates.

    PubMed

    Ashley, T; Plug, A W; Xu, J; Solari, A J; Reddy, G; Golub, E I; Ward, D C

    1995-10-01

    Antibodies against human Rad51 protein were used to examine the distribution of Rad51 on meiotic chromatin in mouse spermatocytes and oocytes as well as chicken oocytes during sequential stages of meiosis. We observed the following dynamic changes in distribution of Rad51 during meiosis: (1) in early leptotene nuclei there are multiple, apparently randomly distributed, foci that by late leptonema become organized into tracks of foci. (2) These foci persist into zygonema, but most foci are now localized on Rad51-positive axes that correspond to lateral elements of the synaptonemal complex. As homologs synapse foci from homologous axes fuse. The distribution and involvement of Rad51 foci as contact points between homologs suggest that they may be components to early recombination nodules. (3) As pachynema progresses the number of foci drops dramatically; the temporal occurrence (mice) and physical and numerical distribution of foci on axes (chickens) suggest that they may be a component of late recombination nodules. (4) In early pachynema there are numerous Rad51 foci on the single axis of the X (mouse spermatocytes) or the Z (chicken oocytes) chromosomes that neither pair, nor recombine. (5) In late pachynema in mouse spermatocytes, but not oocytes, the Rad51 signal is preferentially enhanced at both ends of all the bivalents. As bivalents in spermatocytes, but not oocytes, begin to desynapse at diplonema they are often held together at these Rad51-positive termini. These observations parallel observations that recombination rates are exceptionally high near chromosome ends in male but not female eutherian mammals. (6) From diakinesis through metaphase I, Rad51 protein is detected as low-intensity fluorescent doublets that localize with CREST-specific antigens (kinetochores), suggesting that Rad51 participates, at least as a structural component of the materials involved, in sister kinetochore cohesiveness. Finally, the changes in Rad51 distribution during meiosis do not appear to be species specific, but intrinsic to the meiotic process.

  19. Antagonistic interactions of an arsenic-containing mixture in a multiple organ carcinogenicity bioassay.

    PubMed

    Pott, W A; Benjamin, S A; Yang, R S

    1998-11-27

    Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and trichloroethylene (TCE) are frequently identified as groundwater contaminants near hazardous waste disposal sites. While the carcinogenicity of each of these chemicals has been extensively studied individually, little information exists regarding their carcinogenic potential in combination. Therefore, we investigated the carcinogenic promoting potential of chemical mixtures containing arsenic, DCE, VC and TCE following multiple initiator administration in a multiple organ carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.), Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57, Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of this four-chemical mixture on the development of preneoplastic hepatic lesions (altered hepatocellular foci and glutathione S-transferase pi positive foci) as well as bronchioalveolar hyperplasia and adenoma formation.

  20. 7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

  1. 7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

  2. 7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

  3. 7 CFR 360.301 - Information required for applications for permits to move noxious weeds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... move noxious weeds. 360.301 Section 360.301 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.301 Information required for applications for permits to move noxious weeds. (a) Permit to import...

  4. 77 FR 3729 - Notice of Request for Extension of Approval of an Information Collection; Plant Pest, Noxious...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... Collection; Plant Pest, Noxious Weed, and Garbage Regulations AGENCY: Animal and Plant Health Inspection... with plant pest, noxious weed, and garbage regulations. DATES: We will consider all comments that we... pest, noxious weed, and garbage regulations, contact Dr. Shirley Wager- Pag[eacute], Chief, Pest Permit...

  5. 7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

  6. 7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

  7. 7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

  8. 7 CFR 360.302 - Consideration of applications for permits to move noxious weeds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... noxious weeds. 360.302 Section 360.302 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.302 Consideration of applications for permits to move noxious weeds. Upon the receipt of an application made in...

  9. 7 CFR 360.300 - General prohibitions and restrictions on the movement of noxious weeds; permits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of noxious weeds; permits. 360.300 Section 360.300 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.300 General prohibitions and restrictions on the movement of noxious weeds; permits. (a) No...

  10. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

  11. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

  12. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

  13. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

  14. 36 CFR 222.8 - Cooperation in control of estray or unbranded livestock, animal diseases, noxious farm weeds, and...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... estray or unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. 222.8 Section... unbranded livestock, animal diseases, noxious farm weeds, and use of pesticides. (a) Insofar as it involves... application and enforcement of all laws and regulations relating to livestock diseases, sanitation and noxious...

  15. 7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Petitions to remove a taxon from the noxious weed...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501 Petitions to remove a taxon from the noxious weed lists. A person may petition the Administrator to remove a...

  16. 75 FR 80343 - Extension of Tolerances for Emergency Exemptions (Multiple Chemicals)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... Timothy grass for control of Banks grass mite in Nevada. This regulation extends time-limited tolerances... fenoxaprop-ethyl in or on grass grown for seed for control of noxious weed species in Oregon. This regulation... on grass forage and grass hay at 0.05 ppm for an additional 3-year period. These tolerances will...

  17. Characterization of Foci and Breakthrough Sites During Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: Studies Using High-Density (510-512 Electrodes) Biatrial Epicardial Mapping.

    PubMed

    Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Markowitz, Alan; Waldo, Albert L

    2017-03-17

    We previously demonstrated that persistent and long-standing persistent atrial fibrillation is maintained by activation emanating from foci and breakthrough sites of different cycle lengths (CLs). The purpose of this study was to characterize the behavior of focal and nonrandom breakthrough activation identified during high-density mapping of atrial fibrillation in these patients. During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 epicardial electrodes along with ECG lead II in 12 patients with persistent and long-standing persistent atrial fibrillation. For each patient, analysis of 32 consecutive seconds of activation from identified focal (sustained and/or intermittent) and nonrandom breakthrough sites was performed. Multiple foci (sustained and/or intermittent) of different CLs were present in both atria in 11 of 12 patients; 8 foci were sustained, and 22 were intermittent. Temporal CL behavior of sustained foci varied over time (≤20 ms of the mean CL). For intermittent foci, no activation periods were due to a spontaneous pause (18 of 22) or activation of the focus by another wave front (11 of 22). All patients had breakthrough activation. Seven patients had 12 nonrandom breakthrough sites. Periods of no breakthrough activation were caused by a spontaneous pause (6 of 12 patients) or activation from another wave front (4 of 12) or were uncertain (5 of 12). Focal and nonrandom breakthrough activation sometimes produced repetitive "wannabe" (incomplete) reentry in 6 of 12 patients. During persistent and long-standing persistent atrial fibrillation, sustained foci manifested variable CLs. Spontaneous pauses or activation from other wave fronts explained the intermittency of foci and nonrandom breakthrough. Focal and nonrandom breakthrough activation occasionally produced wannabe reentry. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  18. Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

    PubMed Central

    Johnson, Wayne A.; Carder, Justin W.

    2012-01-01

    A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719

  19. Synaptic control of local translation: the plot thickens with new characters.

    PubMed

    Thomas, María Gabriela; Pascual, Malena Lucía; Maschi, Darío; Luchelli, Luciana; Boccaccio, Graciela Lidia

    2014-06-01

    The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

  20. 7 CFR 360.304 - Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Denial of an application for a permit to move a noxious weed; cancelation of a permit to move a noxious weed. 360.304 Section 360.304 Agriculture..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.304 Denial of an application for a permit to move a...

  1. Learning with Multiple Representations: Infographics as Cognitive Tools for Authentic Learning in Science Literacy

    ERIC Educational Resources Information Center

    Gebre, Engida

    2018-01-01

    This paper presents a descriptive case study where infographics--visual representation of data and ideas--have been used as cognitive tools to facilitate learning with multiple representations in the context of secondary school students' science news reporting. Despite the complementary nature of the two research foci, studies on cognitive tools…

  2. Identifying aggressive prostate cancer foci using a DNA methylation classifier.

    PubMed

    Mundbjerg, Kamilla; Chopra, Sameer; Alemozaffar, Mehrdad; Duymich, Christopher; Lakshminarasimhan, Ranjani; Nichols, Peter W; Aron, Manju; Siegmund, Kimberly D; Ukimura, Osamu; Aron, Monish; Stern, Mariana; Gill, Parkash; Carpten, John D; Ørntoft, Torben F; Sørensen, Karina D; Weisenberger, Daniel J; Jones, Peter A; Duddalwar, Vinay; Gill, Inderbir; Liang, Gangning

    2017-01-12

    Slow-growing prostate cancer (PC) can be aggressive in a subset of cases. Therefore, prognostic tools to guide clinical decision-making and avoid overtreatment of indolent PC and undertreatment of aggressive disease are urgently needed. PC has a propensity to be multifocal with several different cancerous foci per gland. Here, we have taken advantage of the multifocal propensity of PC and categorized aggressiveness of individual PC foci based on DNA methylation patterns in primary PC foci and matched lymph node metastases. In a set of 14 patients, we demonstrate that over half of the cases have multiple epigenetically distinct subclones and determine the primary subclone from which the metastatic lesion(s) originated. Furthermore, we develop an aggressiveness classifier consisting of 25 DNA methylation probes to determine aggressive and non-aggressive subclones. Upon validation of the classifier in an independent cohort, the predicted aggressive tumors are significantly associated with the presence of lymph node metastases and invasive tumor stages. Overall, this study provides molecular-based support for determining PC aggressiveness with the potential to impact clinical decision-making, such as targeted biopsy approaches for early diagnosis and active surveillance, in addition to focal therapy.

  3. Guidelines for management of noxious weeds at Hanford

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

    Roos, R.C.; Malady, M.B.

    1995-10-27

    Integrated Pest Management Services is responsible for management and control of noxious weeds on the Hanford Site. Weed species and populations are prioritized and objective defined, according to potential site and regional impact. Population controls are implemented according to priority. An integrated approach is planned for noxious weed control in which several management options are considered and implemented separately or in coordination to best meet management objectives. Noxious weeds are inventories and monitored to provide information for planning and program review.

  4. Topographic effects on dispersal patterns of Phytophthora cinnamomi at a stand scale in a Spanish heathland

    PubMed Central

    Acedo, Angel; Abad, Enrique

    2018-01-01

    Phytophthora cinnamomi is one of the most important plant pathogens in the world, causing root rot in more than a thousand plant species. This observational study was carried out on a P. cinnamomi infected heathland of Erica umbellata used as goat pasture. The patterns and shapes of disease foci and their distribution were described in a spatial and temporal context using an aerial photograph record. A set of topographic traits was selected on the basis of a disease dynamic hypothesis and their effects on observed spatial disease patterns were analyzed. Incipient infections situated in flat terrain expanded as compact circular front patterns with a low growth rate. On slopes, disease patches developed more rapidly down slope, forming parabolic shapes. The axis direction of the parabolas was highly correlated with terrain aspect, while the parabolic amplitude was associated with land curvature and slope. New secondary foci appeared over the years producing an accelerated increase of the affected surface. These new foci were observed in sites where disease density was higher or near sites more frequently visited by animals such as the stable or the forage crop. In contrast, a smaller number of disease foci occur in areas which animals are reluctant to visit, such as where they have a short range of vision. Our results suggest that 1) the growth of existing P. cinnamomi foci is controlled by a combination of root-to-root contact and water flows, 2) the increase in the diseased area arises mainly from the multiplication of patches, 3) the formation of new foci is mediated by long-distance transport due to the movement of animals and humans along certain preferential pathways, and 4) geomorphology and topography traits are associated with the epidemiology of this soil-borne pathogen. PMID:29601576

  5. Multistability in Chua's circuit with two stable node-foci

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

    Bao, B. C.; Wang, N.; Xu, Q.

    2016-04-15

    Only using one-stage op-amp based negative impedance converter realization, a simplified Chua's diode with positive outer segment slope is introduced, based on which an improved Chua's circuit realization with more simpler circuit structure is designed. The improved Chua's circuit has identical mathematical model but completely different nonlinearity to the classical Chua's circuit, from which multiple attractors including coexisting point attractors, limit cycle, double-scroll chaotic attractor, or coexisting chaotic spiral attractors are numerically simulated and experimentally captured. Furthermore, with dimensionless Chua's equations, the dynamical properties of the Chua's system are studied including equilibrium and stability, phase portrait, bifurcation diagram, Lyapunov exponentmore » spectrum, and attraction basin. The results indicate that the system has two symmetric stable nonzero node-foci in global adjusting parameter regions and exhibits the unusual and striking dynamical behavior of multiple attractors with multistability.« less

  6. Multiparameter behavioral profiling reveals distinct thermal response regimes in Caenorhabditis elegans

    PubMed Central

    2012-01-01

    Background Responding to noxious stimuli by invoking an appropriate escape response is critical for survival of an organism. The sensations of small and large changes in temperature in most organisms have been studied separately in the context of thermotaxis and nociception, respectively. Here we use the nematode C. elegans to address the neurogenetic basis of responses to thermal stimuli over a broad range of intensities. Results C. elegans responds to aversive temperature by eliciting a stereotypical behavioral sequence. Upon sensation of the noxious stimulus, it moves backwards, turns and resumes forward movement in a new direction. In order to study the response of C. elegans to a broad range of noxious thermal stimuli, we developed a novel assay that allows simultaneous characterization of multiple aspects of escape behavior elicited by thermal pulses of increasing amplitudes. We exposed the laboratory strain N2, as well as 47 strains with defects in various aspects of nervous system function, to thermal pulses ranging from ΔT = 0.4°C to 9.1°C and recorded the resulting behavioral profiles. Conclusions Through analysis of the multidimensional behavioral profiles, we found that the combinations of molecules shaping avoidance responses to a given thermal pulse are unique. At different intensities of aversive thermal stimuli, these distinct combinations of molecules converge onto qualitatively similar stereotyped behavioral sequences. PMID:23114012

  7. 7 CFR 360.100 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...

  8. 7 CFR 360.100 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.100 Definitions. As used in this part, words in the... in this definition. Noxious weed. Any plant or plant product that can directly or indirectly injure... Administrator to move plants, plant products, biological control organisms, plant pests, noxious weeds, or...

  9. The economic cost of noxious weeds on Montana grazing lands

    USDA-ARS?s Scientific Manuscript database

    We distributed a 16-question survey concerning noxious weed abundances, impacts and management to livestock producers grazing on privately-owned or leased grazing lands in Montana. The noxious weeds most commonly reported as being present on respondents’ grazing units were Canada thistle (64% of gra...

  10. Sarcocystosis in a stillborn lamb

    USDA-ARS?s Scientific Manuscript database

    Confirmed congenital sarcocystosis has not been reported in sheep and extremely rarely in other domestic ruminants. Sarcocystosis was diagnosed in a stillborn lamb with microscopic lesions predominantly in the central nervous system and placenta. Encephalitis was characterized by multiple foci of gl...

  11. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

  12. 7 CFR 352.10 - Inspection; safeguards; disposal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

  13. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

  14. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

  15. 7 CFR 301.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

  16. 7 CFR 352.3 - Enforcement and administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... administration. (a) Plants, plant products, plant pests, noxious weeds, soil, and other products and articles... pests, noxious weeds, soil, or other products or articles in violation of this part will be subject to... of plants, plant products, plant pests, noxious weeds, soil, or other products or articles subject to...

  17. 7 CFR 352.10 - Inspection; safeguards; disposal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

  18. 7 CFR 301.1 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

  19. 7 CFR 352.10 - Inspection; safeguards; disposal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

  20. 7 CFR 301.1 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... noxious weeds if the Secretary has issued a regulation or order to prevent the dissemination of the biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

  1. 7 CFR 352.10 - Inspection; safeguards; disposal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... specified by him to prevent plant pest or noxious weed dissemination. In the case of prohibited or... commensurate with the risk of plant pest or noxious weed dissemination required to transfer the products or... of the inspector, considerations of risk of plant pest or noxious weed dissemination require, such...

  2. Not in whose backyard? Minority population concentrations and noxious facility sites

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

    Nieves, L.A.

    1992-04-01

    The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people`s reluctance to live near noxious facilities, in whose backyard are such facilities located? This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.

  3. Not in whose backyard Minority population concentrations and noxious facility sites

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

    Nieves, L.A.

    1992-01-01

    The NIMBY (not in may backyard) syndrome has become the nemesis of facility siting efforts in the USA. Given people's reluctance to live near noxious facilities, in whose backyard are such facilities located This study employs US county-level data to examine relative concentrations of minorities living near noxious facilities. Facility types analyzed include electric generating plants, manufacturing plants, Superfund sites, and radioactive waste disposal sites. While this study does not address which cam first, the minority population concentration or the noxious facilities, it documents their current degree of association.

  4. Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin.

    PubMed

    Yoshihara, Kohei; Matsuda, Tsuyoshi; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

    2018-05-03

    The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca 2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca 2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca 2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. Carborundum, a bulk similar to dietary fibers but chemically inert, does not decrease colon carcinogenesis.

    PubMed

    Corpet, D E; Taché, S; Peiffer, G

    1997-03-19

    Dietary fibers might lower the risk of colorectal cancer, maybe because of their bulking effect. We tested the protection afforded by an inert bulk against carcinogenesis. Thirty rats received an azoxymethane injection and were allocated to a control diet, or to a diet supplemented with 10% carborundum. After 100 days the colons were scored for aberrant crypt foci. Compared to controls, the fecal weight was doubled in carborundum-fed rats (P < 0.001), but the aberrant crypt foci multiplicity was not changed (P = 0.92). The results do not support the hypothesis that intestinal dilution by an inert bulk can protect against colon cancer.

  6. 7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 5 2014-01-01 2014-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

  7. 7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

  8. 7 CFR 360.501 - Petitions to remove a taxon from the noxious weed lists.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 5 2012-01-01 2012-01-01 false Petitions to remove a taxon from the noxious weed lists. 360.501 Section 360.501 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.501...

  9. 7 CFR 360.600 - Preemption of State and local laws.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

  10. 7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

  11. 7 CFR 360.600 - Preemption of State and local laws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

  12. 7 CFR 352.6 - Application for permit and approval or denial thereof.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

  13. 7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

  14. 7 CFR 352.6 - Application for permit and approval or denial thereof.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

  15. 7 CFR 352.6 - Application for permit and approval or denial thereof.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... noxious weeds). Except as otherwise provided in this paragraph, any person desiring to unload or land, or... to eliminate danger of plant pest or noxious weed dissemination may be specified in the permit, or... is not possible to prescribe conditions adequate to prevent danger of plant pest or noxious weed...

  16. 7 CFR 360.600 - Preemption of State and local laws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

  17. 7 CFR 360.600 - Preemption of State and local laws.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.600 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

  18. 7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... local laws. (a) Importations of plants, plant products, plant pests, noxious weeds, soil, and other products and articles that may be infested or infected by or contain plant pests or noxious weeds are... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant...

  19. 7 CFR 360.400 - Preemption of State and local laws.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE NOXIOUS WEED REGULATIONS § 360.400 Preemption of State and... subdivision of a State may not regulate in foreign commerce any noxious weed in order to control it, eradicate... prohibitions or restrictions upon the movement in interstate commerce of noxious weeds if the Secretary has...

  20. Intrathecal treatment with MK-801 suppresses thermal nociceptive responses and prevents c-fos immunoreactivity induced in rat lumbar spinal cord neurons.

    PubMed

    Huang, W; Simpson, R K

    1999-09-01

    Sensitization of the second order neurons in the spinal dorsal horn after somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor. These neurons also express c-Fos immunoreactivity in response to the somatic noxious stimuli. The present study assessed the influence of intrathecal pre-treatment with MK-801, a non-competitive antagonist of NMDA receptor, on thermal sensitization following peripheral noxious heat stimulation. In addition, the influence of MK-801 on c-Fos immunoreactivity in the rat lumbar spinal cord neurons after the peripheral noxious heat was examined. Sprague-Dawley rats were subject to intrathecal catheterization and administration of MK-801 or saline before and after noxious heat (52 degrees C) stimulation of rat hindpaws. Thermal sensitization was tested after MK-801 (0.1 mumol 10 microliters-1). Fos-like immunoreactivity was evaluated 2 h after noxious stimulation in a separate group of animals. MK-801 significantly increased the thermal withdrawal threshold by 60% following noxious heat stimulation and reduced c-Fos immunoreactivity in the second order neurons by 70% in the dorsal horn. The study suggests that glutamate plays a pivotal role in the thermal nociceptive pathway and indicates that the NMDA receptor is necessary to maintain normal thermal sensitization, possibly by regulating c-fos gene expression in second order neurons.

  1. Management of hepatocellular adenoma: Solitary-uncomplicated, multiple and ruptured tumors

    PubMed Central

    Toso, Christian; Majno, Pietro; Andres, Axel; Rubbia-Brandt, Laura; Berney, Thierry; Buhler, Léo; Morel, Philippe; Mentha, Gilles

    2005-01-01

    AIM: While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS: Twenty-five consecutive patients operated for solitary-uncomplicated (9), multiple (6), and ruptured (10) HAs were reviewed according to management strategies and outcomes. RESULTS: All solitary-uncomplicated HAs (ranged 2.2-14 cm in size) were removed. Out of 25 HAs, 2 (8%) included foci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA (ranged 1.7-10 cm in size) were initially managed with hemodynamic support and angiography, allowing the embolization of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d (range 4-70 d) after admission. CONCLUSION: Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery. PMID:16237767

  2. Dalmatian toadflax, an invasive exotic noxious weed, threatens Flagstaff pennyroyal community following prescribed fire

    Treesearch

    Barbara Goodrich Phillips; Debra Crisp

    2001-01-01

    Many noxious weed infestations are initiated or increased by soil disturbance. With the recent emphasis on reintroduction of fire into natural ecosystems there has been increased interest in the effects of noxious weeds following fires. This paper discusses the effects of fire on Flagstaff pennyroyal, a Forest Service Region 3 sensitive plant, and the subsequent...

  3. Behavioral and Functional Assays for Investigating Mechanisms of Noxious Cold Detection and Multimodal Sensory Processing in Drosophila Larvae

    PubMed Central

    Patel, Atit A.; Cox, Daniel N.

    2017-01-01

    To investigate cellular, molecular and behavioral mechanisms of noxious cold detection, we developed cold plate behavioral assays and quantitative means for evaluating the predominant noxious cold-evoked contraction behavior. To characterize neural activity in response to noxious cold, we implemented a GCaMP6-based calcium imaging assay enabling in vivo studies of intracellular calcium dynamics in intact Drosophila larvae. We identified Drosophila class III multidendritic (md) sensory neurons as multimodal sensors of innocuous mechanical and noxious cold stimuli and to dissect the mechanistic bases of multimodal sensory processing we developed two independent functional assays. First, we developed an optogenetic dose response assay to assess whether levels of neural activation contributes to the multimodal aspects of cold sensitive sensory neurons. Second, we utilized CaMPARI, a photo-switchable calcium integrator that stably converts fluorescence from green to red in presence of high intracellular calcium and photo-converting light, to assess in vivo functional differences in neural activation levels between innocuous mechanical and noxious cold stimuli. These novel assays enable investigations of behavioral and functional roles of peripheral sensory neurons and multimodal sensory processing in Drosophila larvae. PMID:28835907

  4. Extrachromosomal Nucleolus-Like Compartmentalization by a Plasmid-Borne Ribosomal RNA Operon and Its Role in Nucleoid Compaction.

    PubMed

    Mata Martin, Carmen; Sun, Zhe; Zhou, Yan Ning; Jin, Ding Jun

    2018-01-01

    In the fast-growing Escherichia coli cells, RNA polymerase (RNAP) molecules are concentrated and form foci at clusters of ribosomal RNA (rRNA) operons resembling eukaryotic nucleolus. The bacterial nucleolus-like organization, spatially compartmentalized at the surface of the compact bacterial chromosome (nucleoid), serves as transcription factories for rRNA synthesis and ribosome biogenesis, which influences the organization of the nucleoid. Unlike wild type that has seven rRNA operons in the genome in a mutant that has six (Δ6 rrn ) rRNA operons deleted in the genome, there are no apparent transcription foci and the nucleoid becomes uncompacted, indicating that formation of RNAP foci requires multiple copies of rRNA operons clustered in space and is critical for nucleoid compaction. It has not been determined, however, whether a multicopy plasmid-borne rRNA operon (p rrnB ) could substitute the multiple chromosomal rRNA operons for the organization of the bacterial nucleolus-like structure in the mutants of Δ6 rrn and Δ7 rrn that has all seven rRNA operons deleted in the genome. We hypothesized that extrachromosomal nucleolus-like structures are similarly organized and functional in trans from p rrnB in these mutants. In this report, using multicolor images of three-dimensional superresolution Structured Illumination Microscopy (3D-SIM), we determined the distributions of both RNAP and NusB that are a transcription factor involved in rRNA synthesis and ribosome biogenesis, p rrnB clustering, and nucleoid structure in these two mutants in response to environmental cues. Our results found that the extrachromosomal nucleolus-like organization tends to be spatially located at the poles of the mutant cells. In addition, formation of RNAP foci at the extrachromosomal nucleolus-like structure condenses the nucleoid, supporting the idea that active transcription at the nucleolus-like organization is a driving force in nucleoid compaction.

  5. Modelling dengue epidemic spreading with human mobility

    NASA Astrophysics Data System (ADS)

    Barmak, D. H.; Dorso, C. O.; Otero, M.

    2016-04-01

    We explored the effect of human mobility on the spatio-temporal dynamics of Dengue with a stochastic model that takes into account the epidemiological dynamics of the infected mosquitoes and humans, with different mobility patterns of the human population. We observed that human mobility strongly affects the spread of infection by increasing the final size and by changing the morphology of the epidemic outbreaks. When the spreading of the disease is driven only by mosquito dispersal (flight), a main central focus expands diffusively. On the contrary, when human mobility is taken into account, multiple foci appear throughout the evolution of the outbreaks. These secondary foci generated throughout the outbreaks could be of little importance according to their mass or size compared with the largest main focus. However, the coalescence of these foci with the main one generates an effect, through which the latter develops a size greater than the one obtained in the case driven only by mosquito dispersal. This increase in growth rate due to human mobility and the coalescence of the foci are particularly relevant in temperate cities such as the city of Buenos Aires, since they give more possibilities to the outbreak to grow before the arrival of the low-temperature season. The findings of this work indicate that human mobility could be the main driving force in the dynamics of vector epidemics.

  6. Evaluation of cholesteatoma: our experience with DW Propeller imaging.

    PubMed

    Karandikar, Amit; Loke, Siu Cheng; Goh, Julian; Yeo, Seng Beng; Tan, Tiong Yong

    2015-09-01

    Cholesteatoma management includes early detection and surgical exploration. Due to its tendency to recur, it can be potentially locally aggressive. Magnetic resonance imaging (MRI), and in particular diffusion weighted imaging (DWI), plays an important role in management of these lesions. To assess the accuracy of Propeller (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) DW sequence in detecting middle ear and mastoid cholesteatomas in non-operated ears by surgical correlation. A retrospective review of 15 patients was done who underwent Propeller DWI with either clinically confirmed or suspected cholesteatomas. Surgical correlation was done in all cases. All patients had hyperintense foci on Propeller DWI. Surgical correlation performed revealed that 13 patients had cholesteatomas while two patients had mastoid abscesses. The location, extent, and size of cholesteatomas on Propeller DWI matched with the operative findings. Of the 13 patients with cholesteatomas, three patients had multiple foci of hyperintensity on Propeller DWI, which corroborated with the surgical finding of multiple cholesteatomas. The average apparent diffusion coefficient value of cholesteatoma was 0.868 × 10(-3) mm(2)/s, found to be higher than that of abscess, which was 0.425 × 10(-3) mm(2)/s. Propeller DWI was accurate in assessing the location, extent, and size of cholesteatomas as corroborated with surgical findings. Propeller DWI is useful in detecting number of cholesteatoma foci, a vital finding as it may impact the choice of surgery. © The Foundation Acta Radiologica 2014.

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

    Hutchinson, Kenneth

    To perform remedial vegetation management for keeping vegetation a safe distance away from electric power facilities and controlling noxious weeds within a section of BPA's Big Eddy-Ostrander Transmission Corridor. During a site review conducted in late fall of 2001, the inspector observed various species of hardwood trees resprouted from stumps. The new vegetative growth encroached on the required “Minimum Safe Distance” between the top of vegetation and the conductor cables. The management action is necessary to reduce the current and potential future hazards that tall-growing vegetation poses to transmission conductors. In addition, BPA will include weed control as part ofmore » their remedial vegetation management action. Noxious weeds occur within the corridor. Under a 1999 Executive Order, all federal agencies are required to detect and control noxious weeds. In addition, BPA is required under the 1990 amendment to the Noxious Weed Act (7 USC 2801-2814) to manage undesirable plants on federal land. Also, the Bonneville Power Administration (BPA) has responsibility to manage noxious weeds under the Transmission System Vegetation Management Program Final Environmental Impact Statement (FEIS).1 State statutes and regulations also mandate action by BPA and the USFS to control noxious weeds. The Oregon Department of Agriculture (ODA) has requested that agencies aggressively control these weeds before additional spread occurs.« less

  8. Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

    PubMed

    Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

    2010-08-15

    This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. Histiocytic Sarcoma and Bilateral Facial Vein Thrombosis in a Siberian Hamster (Phodopus sungorus).

    PubMed

    Coble, Dondrae J; Shoemaker, Margaret; Harrington, Bonnie; Dardenne, Adrienne D; Bolon, Brad

    2015-04-01

    A 21-mo-old, male Siberian hamster (Phodopus sungorus) presented with left-sided facial swelling, proptosis of the left eye, and blepharospasm of the right eye. The hamster had been used only for breeding. Because of the poor prognosis, the hamster was euthanized without additional diagnostic assays or treatments. Routine gross pathologic evaluation demonstrated exophthalmos and presumptive hyphema of the left eye, bilateral facial edema, freely movable nodules within the mesentery, white foci within the liver, and a large mass effacing the cranial pole of the right kidney. On histologic evaluation, the mesenteric nodules and liver foci expressed histiocytic marker CD163 and thus were diagnosed as sites of histiocytic sarcoma, whereas the kidney mass was a well-differentiated renal cell carcinoma. The facial swelling resulted from bilateral, chronic, severe, branching thrombi in many facial veins. Additional age-related histopathologic findings were observed in other organs, including diffuse glomerulopathy, nesidioblastosis (pancreatic islet neoformation), and multiple foci of severe cartilage degeneration in the axial skeleton. To our knowledge, this report provides the first description of histiocytic sarcoma in a Siberian hamster.

  10. Systemic phaeohyphomycosis caused by Xylohypha bantiana in a dog.

    PubMed

    Schroeder, H; Jardine, J E; Davis, V

    1994-12-01

    An 8-year-old, Maltese-cross bitch presented with chronic neck and back pain and an acute onset of circling, hyperaesthesia and constant crying. Clinical examination revealed temporal muscle atrophy, an abnormal hanging reflex, cervical rigidity and severe hepatomegaly. Ultrasonography of the liver showed several disseminated, poorly demarcated, hypoechoic areas which on fine needle aspirates, contained large numbers of pigmented fungal hyphae. Cerebrospinal fluid examination revealed fungal hyphae and numerous Ehrlichia canis morulae. A diagnosis of systemic phaeohyphomycosis secondary to ehrlichiosis was proposed. Treatment was unsuccessful and the dog was euthanased. At necropsy, multiple yellowish-green to black, necro-granulomatous foci were found throughout the liver parenchyma and similar foci were present in the spleen, renal cortices and adrenal glands. Irregular, multifocal, grey to black foci of malacia were present in both the grey and the white matter of the brain. On histopathological examination pigmented fungal hyphae were demonstrated in the liver, spleen, kidneys, portal lymph node and adrenals, as well as in the brain. Cultures of various organs yielded a fungal organism identified as Xylohypha bantiana.

  11. Physical Environments of Assisted Living: Research Needs and Challenges

    ERIC Educational Resources Information Center

    Cutler, Lois J.

    2007-01-01

    Purpose: This article aims to review research measures and findings related to physical environments of assisted living (AL) according to multiple conceptual perspectives--ecological, cultural, and Maslovian hierarchy. Design and Methods: A literature and research review was undertaken with two foci: performance measures for physical environments,…

  12. Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis

    PubMed Central

    Georgescu, Walter; Osseiran, Alma; Rojec, Maria; Liu, Yueyong; Bombrun, Maxime; Tang, Jonathan; Costes, Sylvain V.

    2015-01-01

    Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation. PMID:26107175

  13. Characterizing the DNA damage response by cell tracking algorithms and cell features classification using high-content time-lapse analysis

    DOE PAGES

    Georgescu, Walter; Osseiran, Alma; Rojec, Maria; ...

    2015-06-24

    Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR) with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF) across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A) expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were ablemore » to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm 2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when too many DSB occur at once. High doses of ionizing radiation lead to RIF merging into repair domains which in turn increases DSB proximity and misrepair. Furthermore, such finding may therefore be critical to explain the supralinear dose dependence for chromosomal rearrangement and cell death measured after exposure to ionizing radiation.« less

  14. From pest data to abundance-based risk maps combining eco-physiological knowledge, weather, and habitat variability.

    PubMed

    Lacasella, Federica; Marta, Silvio; Singh, Aditya; Stack Whitney, Kaitlin; Hamilton, Krista; Townsend, Phil; Kucharik, Christopher J; Meehan, Timothy D; Gratton, Claudio

    2017-03-01

    Noxious species, i.e., crop pest or invasive alien species, are major threats to both natural and managed ecosystems. Invasive pests are of special importance, and knowledge about their distribution and abundance is fundamental to minimize economic losses and prioritize management activities. Occurrence models are a common tool used to identify suitable zones and map priority areas (i.e., risk maps) for noxious species management, although they provide a simplified description of species dynamics (i.e., no indication on species density). An alternative is to use abundance models, but translating abundance data into risk maps is often challenging. Here, we describe a general framework for generating abundance-based risk maps using multi-year pest data. We used an extensive data set of 3968 records collected between 2003 and 2013 in Wisconsin during annual surveys of soybean aphid (SBA), an exotic invasive pest in this region. By using an integrative approach, we modelled SBA responses to weather, seasonal, and habitat variability using generalized additive models (GAMs). Our models showed good to excellent performance in predicting SBA occurrence and abundance (TSS = 0.70, AUC = 0.92; R 2  = 0.63). We found that temperature, precipitation, and growing degree days were the main drivers of SBA trends. In addition, a significant positive relationship between SBA abundance and the availability of overwintering habitats was observed. Our models showed aphid populations were also sensitive to thresholds associated with high and low temperatures, likely related to physiological tolerances of the insects. Finally, the resulting aphid predictions were integrated using a spatial prioritization algorithm ("Zonation") to produce an abundance-based risk map for the state of Wisconsin that emphasized the spatiotemporal consistency and magnitude of past infestation patterns. This abundance-based risk map can provide information on potential foci of pest outbreaks where scouting efforts and prophylactic measures should be concentrated. The approach we took is general, relatively simple, and can be applied to other species, habitats and geographical areas for which species abundance data and biotic and abiotic data are available. © 2016 by the Ecological Society of America.

  15. Cat's medullary reticulospinal and subnucleus reticularis dorsalis noxious neurons form a coupled neural circuit through collaterals of descending axons

    PubMed Central

    Leiras, Roberto; Martín-Cora, Francisco; Velo, Patricia; Liste, Tania

    2015-01-01

    Animals and human beings sense and react to real/potential dangerous stimuli. However, the supraspinal mechanisms relating noxious sensing and nocifensive behavior are mostly unknown. The collateralization and spatial organization of interrelated neurons are important determinants of coordinated network function. Here we electrophysiologically studied medial medullary reticulospinal neurons (mMRF-RSNs) antidromically identified from the cervical cord of anesthetized cats and found that 1) more than 40% (79/183) of the sampled mMRF-RSNs emitted bifurcating axons running within the dorsolateral (DLF) and ventromedial (VMF) ipsilateral fascicles; 2) more than 50% (78/151) of the tested mMRF-RSNs with axons running in the VMF collateralized to the subnucleus reticularis dorsalis (SRD) that also sent ipsilateral descending fibers bifurcating within the DLF and the VMF. This percentage of mMRF collateralization to the SRD increased to more than 81% (53/65) when considering the subpopulation of mMRF-RSNs responsive to noxiously heating the skin; 3) reciprocal monosynaptic excitatory relationships were electrophysiologically demonstrated between noxious sensitive mMRF-RSNs and SRD cells; and 4) injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin evidenced mMRF to SRD and SRD to mMRF projections contacting the soma and proximal dendrites. The data demonstrated a SRD-mMRF network interconnected mainly through collaterals of descending axons running within the VMF, with the subset of noxious sensitive cells forming a reverberating circuit probably amplifying mutual outputs simultaneously regulating motor activity and spinal noxious afferent input. The results provide evidence that noxious stimulation positively engages a reticular SRD-mMRF-SRD network involved in pain-sensory-to-motor transformation and modulation. PMID:26581870

  16. Diffuse noxious inhibitory control. Reappraisal by pain-related somatosensory evoked potentials following CO2 laser stimulation.

    PubMed

    Kakigi, R

    1994-09-01

    The effects of DNIC (diffuse noxious inhibitory control) in humans were evaluated by means of pain SEPs (somatosensory evoked potentials) and pain visual analogue scale (VAS) following CO2 laser stimulation applied to the left knee while conditioning stimuli (non-noxious and noxious thermal stimuli) applied to the right hand. Pain SEPs were recorded from scalp electrodes following laser stimulation applied to the left knee during various conditions as follows: (1) control (without any interference), (2) non-noxious (dipping the right hand in water at 41 degrees C for 3 min), (3) noxious (dipping the right hand in water at 46 degrees C for 3 min), and (4) after-effect (3-6 min after taking the hand from the water at 46 degrees C). The present pain SEPs findings confirmed the presence of DNIC in humans, and indicates: (1) degree of pain relief was significantly correlated with changes in pain SEPs, particularly a marked decrease in amplitude, and a decrease in VAS; (2) DNIC was more effective on the second pain than the first pain; (3) the effect of DNIC gradually increased over time, but it rapidly disappeared after the conditioning stimuli ceased; and (4) DNIC was not due merely to changes of attention. I propose that the site responsible for DNIC is the brainstem or the spinal cord rather than the cerebral hemisphere.

  17. Activation of planarian TRPA1 by reactive oxygen species reveals a conserved mechanism for nociception

    PubMed Central

    Arenas, Oscar M.; Zaharieva, Emanuela E.; Para, Alessia; Vásquez-Doorman, Constanza; Petersen, Christian P.; Gallio, Marco

    2017-01-01

    All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant flies (Drosophila) are also defective in noxious heat responses. Unexpectedly, we find that either planarian or human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. PMID:29184198

  18. Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

    PubMed

    Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

    2005-12-01

    The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

  19. The Physiology of Bone Pain. How Much Do We Really Know?

    PubMed Central

    Nencini, Sara; Ivanusic, Jason J.

    2016-01-01

    Pain is associated with most bony pathologies. Clinical and experimental observations suggest that bone pain can be derived from noxious stimulation of the periosteum or bone marrow. Sensory neurons are known to innervate the periosteum and marrow cavity, and most of these have a morphology and molecular phenotype consistent with a role in nociception. However, little is known about the physiology of these neurons, and therefore information about mechanisms that generate and maintain bone pain is lacking. The periosteum has received greater attention relative to the bone marrow, reflecting the easier access of the periosteum for experimental assessment. With the electrophysiological preparations used, investigators have been able to record from single periosteal units in isolation, and there is a lot of information available about how they respond to different stimuli, including those that are noxious. In contrast, preparations used to study sensory neurons that innervate the bone marrow have been limited to recording multi-unit activity in whole nerves, and whilst they clearly report responses to noxious stimulation, it is not possible to define responses for single sensory neurons that innervate the bone marrow. There is only limited evidence that peripheral sensory neurons that innervate bone can be sensitized or that they can be activated by multiple stimulus types, and at present this only exists in part for periosteal units. In the central nervous system, it is clear that spinal dorsal horn neurons can be activated by noxious stimuli applied to bone. Some can be sensitized under pathological conditions and may contribute in part to secondary or referred pain associated with bony pathology. Activity related to stimulation of sensory nerves that innervate bone has also been reported in neurons of the spinoparabrachial pathway and the somatosensory cortices, both known for roles in coding information about pain. Whilst these provide some clues as to the way information about bone pain is centrally coded, they need to be expanded to further our understanding of other central territories involved. There is a lot more to learn about the physiology of peripheral sensory neurons that innervate bone and their central projections. PMID:27199772

  20. Duodenal afferent input converges onto T9-T10 spinal neurons responding to gastric distension in rats.

    PubMed

    Qin, Chao; Chen, Jiande D Z; Zhang, Jing; Foreman, Robert D

    2007-12-01

    Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. Extracellular potentials of single T9-T10 spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Graded gastric distensions (GD, 20, 40, 60 mm Hg, 20 s) were induced by air inflation of a latex balloon surgically placed in the stomach. Graded duodenal distensions (DD, 0.2, 0.4, 0.6 ml, 20 s) were produced by water inflation of a latex balloon placed into the duodenum. Of 70 deeper (depth from dorsal surface of spinal cord: 0.3-1.2 mm) spinal neurons responsive to noxious GD (> or =40 mm Hg), 44(63%) also responded to noxious DD (> or =0.4 ml). Similarly, 13/17 (76%) superficial neurons (depth <0.3 mm) responded to both GD and DD. Of 57 gastroduodenal convergent neurons, 41 (72%) had excitatory and 6 had inhibitory responses to both GD and DD; the remaining neurons exhibited multiple patterns of excitation and inhibition. 43/57 (75%) gastroduodenal convergent neurons had low-threshold (< or =20 mm Hg) responses to GD, whereas 42/57 (74%) of these neurons had high-threshold (> or =0.4 ml) responses to DD. In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the stomach and duodenum and play a role in visceral nociception and reflexes.

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

    Hutchinson, Kenneth

    Vegetation Management on sections of the McNary-Ross, McNary-Horse Heaven, Horse Heaven-Harvarlum, Harvarlum-Big Eddy, and Hanford-John Day Transmission lines. The treatment areas are identified in Step 1 of the Planning Steps shown below. The work will involve the control of noxious weeds in the subject rights-of-ways (ROWs). BPA, in cooperation with the various County Noxious Weed Control Boards and associated landowners, will provide resources to assist landowners in controlling noxious weeds on the subject ROWs. The Weed Board will perform all activities on behalf of BPA.

  2. A decade review of publications in Families, Systems, & Health: 2005-2015.

    PubMed

    Mendenhall, Tai J; Li, Yiting; Schulz, Catherine L

    2016-09-01

    The purpose of this investigation was to review recent publication content and trends in Families, Systems, & Health ( FSH ). How do the journal’s articles reflect current and emerging challenges in health care? We hope that our findings can guide special issues and content foci. All work published in FSH between 2005 and 2015 was included (n = 452); each piece was coded for article type, general foci, and specific foci. The most common type of article published over the 10-year time frame was research reports (43%; n = 195), followed by other types (e.g., tribute pieces, poems), commentaries, conceptual/theory papers, literature reviews, and case studies. The most common general focus included family health and/or functioning (28%; n = 128). The most common specific foci centered on children (15%; n = 55). Common themes found in FSH ’s most frequently cited publications included family relationships in care, chronic physical illnesses, and mental health. Marked trends in journal content included increases in articles targeting family health and/or functioning and primary care and decreased attention to theory. FSH’s emphasis on research reports to inform current and evolving interventions that target contemporary health challenges suggests that the journal is keeping stride with the most pressing issues in health care today. Future special issues can continue to serve and meet these needs. FSH’s robust inclusion of other article types sustains the journal’s mission to advance multiple ways of understanding health-care phenomena. PsycINFO Database Record (c) 2016 APA, all rights reserved

  3. Nonword Repetition, Phonological Storage, and Multiple Determinations

    ERIC Educational Resources Information Center

    Gupta, Prahlad

    2006-01-01

    The proposals that (a) nonword repetition and word learning both rely on phonological storage and (b) both are multiply determined are two of the major foci of Gathercole's (2006) Keynote Article, which marshals considerable evidence in support of each. In my view, the importance of these proposals cannot be overstated: these two notions go to the…

  4. Visualising large hierarchies with Flextree

    NASA Astrophysics Data System (ADS)

    Song, Hongzhi; Curran, Edwin P.; Sterritt, Roy

    2003-05-01

    One of the main tasks in Information Visualisation research is creating visual tools to facilitate human understanding of large and complex information spaces. Hierarchies, being a good mechanism in organising such information, are ubiquitous. Although much research effort has been spent on finding useful representations for hierarchies, visualising large hierarchies is still a difficult topic. One of the difficulties is how to show both tructure and node content information in one view. Another is how to achieve multiple foci in a focus+context visualisation. This paper describes a novel hierarchy visualisation technique called FlexTree to address these problems. It contains some important features that have not been exploited so far. In this visualisation, a profile or contour unique to the hierarchy being visualised can be gained in a histogram-like layout. A normalised view of a common attribute of all nodes can be acquired, and selection of this attribute is controllable by the user. Multiple foci are consistently accessible within a global context through interaction. Furthermore it can handle a large hierarchy that contains several thousand nodes in a PC environment. In addition results from an informal evaluation are also presented.

  5. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

    PubMed Central

    2012-01-01

    Background Murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ) signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO) and vice versa (IFNγRperiKO). Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1. Conclusions Alterations in distribution and composition of CNS inflammatory foci are not sufficient for the onset of atypical EAE. IFNγ dictates the course of neuroinflammatory disorders mainly through actions exerted within the CNS. This study provides strong evidence that link microglial STAT1 inactivation to vestibular dysfunction. PMID:22248039

  6. Noxious Weeds in the US and Canada

    Science.gov Websites

    projects • Comments Agricultural Research Service United States Department of Agriculture Noxious weeds in supported by the USDA Agricultural Research Service. Principal investigators: Dr. Kerri Skinner, University

  7. Method of reduction of the number of driving system channels for phased-array transducers using isolation transformers.

    PubMed

    Fjield, T; Hynynen, K

    2000-01-01

    Phased-array technology offers an incredible advantage to therapeutic ultrasound due to the ability to electronically steer foci, create multiple foci, or to create an enlarged focal region by using phase cancellation. However, to take advantage of this flexibility, the phased-arrays generally consist of many elements. Each of these elements requires its own radio-frequency generator with independent amplitude and phase control, resulting in a large, complex, and expensive driving system. A method is presented here where in certain cases the number of amplifier channels can be reduced to a fraction of the number of transducer elements, thereby simplifying the driving system and reducing the overall system complexity and cost, by using isolation transformers to produce 180 degrees phase shifts.

  8. Multifocal fibrosing thyroiditis: report of 55 cases of a poorly recognized entity.

    PubMed

    Fellegara, Giovanni; Rosai, Juan

    2015-03-01

    During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

  9. Magma Reservoirs Feeding Giant Radiating Dike Swarms: Insights from Venus

    NASA Technical Reports Server (NTRS)

    Grosfils, E. B.; Ernst, R. E.

    2003-01-01

    Evidence of lateral dike propagation from shallow magma reservoirs is quite common on the terrestrial planets, and examination of the giant radiating dike swarm population on Venus continues to provide new insight into the way these complex magmatic systems form and evolve. For example, it is becoming clear that many swarms are an amalgamation of multiple discrete phases of dike intrusion. This is not surprising in and of itself, as on Earth there is clear evidence that formation of both magma reservoirs and individual giant radiating dikes often involves periodic magma injection. Similarly, giant radiating swarms on Earth can contain temporally discrete subswarms defined on the basis of geometry, crosscutting relationships, and geochemical or paleomagnetic signatures. The Venus data are important, however, because erosion, sedimentation, plate tectonic disruption, etc. on Earth have destroyed most giant radiating dike swarm's source regions, and thus we remain uncertain about the geometry and temporal evolution of the magma sources from which the dikes are fed. Are the reservoirs which feed the dikes large or small, and what are the implications for how the dikes themselves form? Does each subswarm originate from a single, periodically reactivated reservoir, or do subswarms emerge from multiple discrete geographic foci? If the latter, are these discrete foci located at the margins of a single large magma body, or do multiple smaller reservoirs define the character of the magmatic center as a whole? Similarly, does the locus of magmatic activity change with time, or are all the foci active simultaneously? Careful study of giant radiating dike swarms on Venus is yielding the data necessary to address these questions and constrain future modeling efforts. Here, using giant radiating dike swarms from the Nemesis Tessera (V14) and Carson (V43) quadrangles as examples, we illustrate some of the dike swarm focal region diversity observed on Venus and briefly explore some key implications for the questions framed above.

  10. The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

    PubMed

    Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

    2006-04-01

    Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

  11. Molecular Testing in Multiple Synchronous Lung Adenocarcinomas: Case Report and Literature Review.

    PubMed

    Rafael, Oana C; Lazzaro, Richard; Hasanovic, Adnan

    2016-02-01

    Discovery of driver mutations in pulmonary adenocarcinoma has revolutionized the field of thoracic oncology with major impact on therapy and diagnosis. Testing for EGFR, ALK, and KRAS mutations has become part of everyday practice. We report a case with multiple synchronous primary pulmonary adenocarcinomas in a 72-year-old female with previous history of smoking. The patient presented with cough and bilateral lung ground glass opacities. A positron emission tomography/computed tomography scan showed no activity in mediastinal lymph nodes. She underwent a left upper lobe biopsy and a right upper lobe wedge resection. Pathology revealed 4 morphologically distinct adenocarcinoma foci, suggestive of synchronous primary lung tumors. Molecular testing demonstrated no mutation in the left tumor. Three different driver mutations were present in the right lung tumors: KRAS codon 12 G12D and G12V and EGFR exon 21 L858R mutation, confirming the initial histologic impression. Subsequently, left upper lobe lobectomy showed 3 additional foci of adenocarcinoma with different morphologies, suggestive of synchronous primaries as well. No additional molecular testing was performed. Synchronous pulmonary adenocarcinomas are not uncommon; however, 4 or more synchronous tumors are rare. Distinguishing multiple primary tumors from intrapulmonary metastases is a common problem in thoracic oncology with major implications for staging, prognosis, and treatment. Lung adenocarcinoma subclassification based on predominant and coexisting histologic patterns can greatly facilitate differentiation between intrapulmonary metastases and multiple synchronous tumors. Use of molecular profiling is recommended since it further increases confidence in the diagnostic workup of multiple pulmonary adenocarcinomas and helps guiding therapy. © The Author(s) 2015.

  12. The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson's Disease Patients.

    PubMed

    Belasen, Abigail; Youn, Youngwon; Gee, Lucy; Prusik, Julia; Lai, Brant; Ramirez-Zamora, Adolfo; Rizvi, Khizer; Yeung, Philip; Shin, Damian S; Argoff, Charles; Pilitsis, Julie G

    2016-10-01

    Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits. © 2016 International Neuromodulation Society.

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

    Hermeston, Mark W.

    Franklin County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, and 500 kV ROWs in Franklin County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Franklin County, Washington. In a cooperative effort, BPA, through landowners and the Franklin County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal is tomore » eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less

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

    Hermeston, Mark W.

    Benton County noxious weed management along BPA rights-of-ways, transmission structures, roads, and switches listed in Attachment 1. Attachment 1 identifies the ROW, ROW width, and ROW length of the proposed action. Includes all BPA 115kV, 230kV, 345kV and 500 kV ROWs in Benton County, Washington. BPA proposes to clear noxious and/or unwanted low-growing vegetation in all BPA ROWs in Benton County, Washington. In a cooperative effort, BPA, through landowners and the Benton County Weed Control Board, plan to eradicate noxious plants and other unwanted, low-growing vegetation within the ROW width including all structures and access roads. BPA’s overall goal ismore » to eradicate all noxious and unwanted vegetation through chemical treatment and reseeding. Selective and nonselective chemical treatment using spot, local and broadcast methods. All work will be executed in accordance with the National Electrical Safety Code and BPA standards. Work is to begin in March 2002.« less

  15. Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

    PubMed

    Nir, Rony-Reuven; Sinai, Alon; Moont, Ruth; Harari, Eyal; Yarnitsky, David

    2012-03-01

    Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  16. 78 FR 37777 - Notice of Request for Extension of Approval of an Information Collection; Cooperative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... pests, noxious weeds, and biological control agents, which may be used to control plant pests or noxious... detect, in collaboration with the National Plant Diagnostic Network and the U.S. Department of...

  17. 7 CFR 201.52 - Noxious-weed seeds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the bulk examined for noxious-weed seeds need not be noted: 1/2-gram purity working sample, 16 or more seeds; 1-gram purity working sample, 23 or more seeds; 2-gram purity working sample or larger, 30 or...

  18. Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

    PubMed

    Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

    2018-05-21

    While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an • OH pulse reduced to background the • OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

  19. Canine mammary minute oncocytomas with neuroendocrine differentiation associated with multifocal acinar cell oncocytic metaplasia.

    PubMed

    Nagahara, Rei; Kimura, Masayuki; Itahashi, Megu; Sugahara, Go; Kawashima, Masashi; Murayama, Hirotada; Yoshida, Toshinori; Shibutani, Makoto

    2016-11-01

    Two solitary and minute tumors of 1 and 1.5 mm diameter were identified by microscopy in the left fourth mammary gland of a 13-year-old female Labrador Retriever dog, in addition to multiple mammary gland tumors. The former tumors were well circumscribed and were composed of small-to-large polyhedral neoplastic oncocytes with finely granular eosinophilic cytoplasm, and were arranged in solid nests separated by fine fibrovascular septa. Scattered lumina of variable sizes containing eosinophilic secretory material were evident. Cellular atypia was minimal, and no mitotic figures were visible. One tumor had several oncocytic cellular foci revealing cellular transition, with perivascular pseudorosettes consisting of columnar epithelial cells surrounding the fine vasculature. Scattered foci of mammary acinar cell hyperplasia showing oncocytic metaplasia were also observed. Immunohistochemically, the cytoplasm of neoplastic cells of the 2 microtumors showed diffuse immunoreactivity to anti-cytokeratin antibody AE1/AE3, and finely granular immunoreactivity for 60-kDa heat shock protein, mitochondrial membrane ATP synthase complex V beta subunit, and chromogranin A. One tumor also had oncocytic cellular foci forming perivascular pseudorosettes showing cellular membrane immunoreactivity for neural cell adhesion molecule. The tumors were negative for smooth muscle actin, neuron-specific enolase, vimentin, desmin, S100, and synaptophysin. Ultrastructural observation confirmed the abundant mitochondria in the cytoplasm of both neoplastic and hyperplastic cells, the former cells also having neuroendocrine granule-like electron-dense bodies. From these results, our case was diagnosed with mammary oncocytomas accompanied by neuroendocrine differentiation. Scattered foci of mammary oncocytosis might be related to the multicentric occurrence of these oncocytomas. © 2016 The Author(s).

  20. Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-{beta} induction

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

    Melroe, Gregory T.; Silva, Lindsey; Schaffer, Priscilla A.

    2007-04-10

    The host innate response to viral infection includes the production of interferons, which is dependent on the coordinated activity of multiple transcription factors. Herpes simplex virus 1 (HSV-1) has been shown to block efficient interferon expression by multiple mechanisms. We and others have demonstrated that HSV-1 can inhibit the transcription of genes promoted by interferon regulatory factor-3 (IRF-3), including interferon beta (IFN-{beta}), and that the immediate-early ICP0 protein is sufficient for this function. However, the exact mechanism by which ICP0 blocks IRF-3 activity has yet to be determined. Unlike some other viral proteins that inhibit IRF-3 activity, ICP0 does notmore » appear to affect phosphorylation and dimerization of IRF-3. Here, we show that a portion of activated IRF-3 co-localizes with nuclear foci containing ICP0 at early times after virus infection. Co-localization to ICP0-containing foci is also seen with the IRF-3-binding partners and transcriptional co-activators, CBP and p300. In addition, using immunoprecipitation of infected cell lysates, we can immunoprecipitate a complex containing ICP0, IRF-3, and CBP. Thus we hypothesize that ICP0 recruits activated IRF-3 and CBP/p300 to nuclear structures, away from the host chromatin. This leads to the inactivation and accelerated degradation of IRF-3, resulting in reduced transcription of IFN-{beta} and an inhibition of the host response. Therefore, ICP0 provides an example of how viruses can block IFN-{beta} induction by sequestration of important transcription factors essential for the host response.« less

  1. 33 CFR 151.30 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

  2. 33 CFR 151.30 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

  3. 33 CFR 151.30 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

  4. 33 CFR 151.30 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER... Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.30 Applicability. (a) Except as...

  5. Erysipelas in a free-ranging Hawaiian crow (Corvus hawaiiensis)

    USGS Publications Warehouse

    Work, Thierry M.; Ball, Donna; Wolcott, Mark

    1999-01-01

    We describe a case of erysipelas in a free-ranging endangered Hawaiian crow. The partially scavenged carcass exhibited gross emaciation and petechial hemorrhages in both lungs. Microscopy revealed multiple necrotic foci associated with gram-positive rods in the liver and adrenal, diffuse acute proximal tubular necrosis of kidney, diffuse necrosis and inflammation of proventricular mucosa associated with gram-positive rods, and multiple intravascular aggregates of gram-positive rods associated with thrombi. Culture of the kidney revealed the bacterium to be Erysipelothrix rhusiopathiae. The implications of this finding to free-ranging crows remain unclear.

  6. Live Dynamics of 53BP1 Foci Following Simultaneous Induction of Clustered and Dispersed DNA Damage in U2OS Cells

    PubMed Central

    Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Scherthan, Harry

    2018-01-01

    Cells react differently to clustered and dispersed DNA double strand breaks (DSB). Little is known about the initial reaction to simultaneous induction of DSBs with different complexities. Here, we used live cell microscopy to analyse the behaviour of 53BP1-GFP (green fluorescence protein) foci formation at DSBs induced in U2OS cells by alpha particles, X-rays or mixed beams over a 75 min period post irradiation. X-ray-induced foci rapidly increased and declined over the observation interval. After an initial increase, mixed beam-induced foci remained at a constant level over the observation interval, similarly as alpha-induced foci. The average areas of radiation-induced foci were similar for mixed beams and X-rays, being significantly smaller than those induced by alpha particles. Pixel intensities were highest for mixed beam-induced foci and showed the lowest level of variability over time as compared to foci induced by alphas and X-rays alone. Finally, mixed beam-exposed foci showed the lowest level of mobility as compared to alpha and X-ray exposure. The results suggest paralysation of chromatin around foci containing clustered DNA damage. PMID:29419809

  7. 33 CFR 151.15 - Reporting requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

  8. 33 CFR 151.15 - Reporting requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

  9. 33 CFR 151.15 - Reporting requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND... Treaty as it Pertains to Pollution from Ships Oil Pollution § 151.15 Reporting requirements. (a) The... involves— (1) A discharge of oil, hazardous substances, marine pollutants, or noxious liquid substances...

  10. 75 FR 23220 - Notice of Revision and Request for Extension of Approval of an Information Collection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-03

    ... data on plant pests, noxious weeds, and biological control agents, which may be used to control plant..., eradicate, suppress, control, prevent, or retard the spread of plant pests and noxious weeds that are new to...

  11. A Call for More Religious Education in the Secondary Social Studies Curriculum of Western Canadian Provinces

    ERIC Educational Resources Information Center

    Patrick, Margaretta L.

    2015-01-01

    The inclusion of religion in public education remains contentious in many countries, including Canada. As multiple religions fill the public sphere, some religious education is necessary if Canadians are to understand each other. Social studies is seen as an appropriate subject to include such education given its foci on diversity and citizenship.…

  12. When Simple Harmonic Motion Is Not that Simple: Managing Epistemological Complexity by Using Computer-Based Representations

    ERIC Educational Resources Information Center

    Parnafes, Orit

    2010-01-01

    Many real-world phenomena, even "simple" physical phenomena such as natural harmonic motion, are complex in the sense that they require coordinating multiple subtle foci of attention to get the required information when experiencing them. Moreover, for students to develop sound understanding of a concept or a phenomenon, they need to learn to get…

  13. Effects of reference analgesics and psychoactive drugs on the noxious heat threshold of mice measured by an increasing-temperature water bath.

    PubMed

    Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor

    2013-12-01

    The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

  14. Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity.

    PubMed

    Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah

    2014-11-01

    More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1-12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n=12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n=39), where a subset (n=11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P=0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P=0.30). Experimental tactile (P=0.012) and noxious (P=0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Noxious stimulation in children receiving general anaesthesia evokes an increase in delta frequency brain activity

    PubMed Central

    Hartley, Caroline; Poorun, Ravi; Goksan, Sezgi; Worley, Alan; Boyd, Stewart; Rogers, Richard; Ali, Tariq; Slater, Rebeccah

    2014-01-01

    More than 235,000 children/year in the UK receive general anaesthesia, but it is unknown whether nociceptive stimuli alter cortical brain activity in anaesthetised children. Time-locked electroencephalogram (EEG) responses to experimental tactile stimuli, experimental noxious stimuli, and clinically required cannulation were examined in 51 children (ages 1–12 years) under sevoflurane monoanaesthesia. Based on a pilot study (n = 12), we hypothesised that noxious stimulation in children receiving sevoflurane monoanaesthesia would evoke an increase in delta activity. This was tested in an independent sample of children (n = 39), where a subset (n = 11) had topical local anaesthetic applied prior to stimulation. A novel method of time-locking the stimuli to the EEG recording was developed using an event detection interface and high-speed camera. Clinical cannulation evoked a significant increase (34.2 ± 8.3%) in delta activity (P = 0.042), without concomitant changes in heart rate or reflex withdrawal, which was not observed when local anaesthetic was applied (P = 0.30). Experimental tactile (P = 0.012) and noxious (P = 0.0099) stimulation also evoked significant increases in delta activity, but the magnitude of the response was graded with stimulus intensity, with the greatest increase evoked by cannulation. We demonstrate that experimental and clinically essential noxious procedures, undertaken in anaesthetised children, alter the pattern of EEG activity, that this response can be inhibited by local anaesthetic, and that this measure is more sensitive than other physiological indicators of nociception. This technique provides the possibility that sensitivity to noxious stimuli during anaesthesia could be investigated in other clinical populations. PMID:25218826

  16. Assessment of Responsiveness to Everyday Non-Noxious Stimuli in Pain-Free Migraineurs With Versus Without Aura.

    PubMed

    Granovsky, Yelena; Shor, Merav; Shifrin, Alla; Sprecher, Elliot; Yarnitsky, David; Bar-Shalita, Tami

    2018-03-27

    Migraineurs with aura (MWA) express higher interictal response to non-noxious and noxious experimental sensory stimuli compared with migraineurs without aura (MWoA), but whether these differences also prevail in response to everyday non-noxious stimuli is not yet explored. This is a cross-sectional study testing 53 female migraineurs (30 MWA; 23 MWoA) who underwent a wide battery of noxious psychophysical testing at a pain-free phase, and completed a Sensory Responsiveness Questionnaire and pain-related psychological questionnaires. The MWA group showed higher questionnaire-based sensory over-responsiveness (P = .030), higher magnitude of pain temporal summation (P = .031) as well as higher monthly attack frequency (P = .027) compared with the MWoA group. Overall, 45% of migraineurs described abnormal sensory (hyper- or hypo-) responsiveness; its incidence was higher among MWA (19 of 30, 63%) versus MWoA (6 of 23, 27%, P = .012), with an odds ratio of 3.58 for MWA. Sensory responsiveness scores were positively correlated with attack frequency (r = .361, P = .008) and temporal summation magnitude (r = .390, P = .004), both regardless of migraine type. MWA express higher everyday sensory responsiveness than MWoA, in line with higher response to experimental noxious stimuli. Abnormal scores of sensory responsiveness characterize people with sensory modulation dysfunction, suggesting possible underlying mechanisms overlap, and possibly high incidence of both clinical entities. This article presents findings distinguishing MWA, showing enhanced pain amplification, monthly attack frequency, and over-responsiveness to everyday sensations, compared with MWoA. Further, migraine is characterized by a high incidence of abnormal responsiveness to everyday sensation, specifically sensory over-responsiveness, that was also found related to pain. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  17. Assessment of nociception and pain in participants with unresponsive or minimally conscious state after acquired brain injury: the relationship between the Coma Recovery Scale-Revised and the Nociception Coma Scale-Revised.

    PubMed

    Chatelle, Camille; Hauger, Solveig L; Martial, Charlotte; Becker, Frank; Eifert, Bernd; Boering, Dana; Giacino, Joseph T; Laureys, Steven; Løvstad, Marianne; Maurer-Karattup, Petra

    2018-04-10

    Investigate the relationship between consciousness and nociceptive responsiveness (i.e., Nociception Coma Scale-Revised [NCS-R]), examine the suitability of the NCS-R for assessing nociception in participants with disorders of consciousness (DoC) and replicate previous findings on psychometric properties of the scale. We prospectively assessed consciousness with the Coma Recovery Scale-Revised (CRS-R). Responses during baseline, non-noxious and noxious stimulations were scored with the NCS-R, CRS-R oromotor and motor subscales. Specialized DoC program and university hospitals. Eighty-five participants diagnosed with DoCs. Correlation between CRS-R total scores and CRS-R and NCS-R (sub)scores to noxious stimulation, proportion of grimace and/or cry in participants with minimally consciousness (MCS) and unresponsive wakefulness syndrome (UWS) during non-noxious and noxious conditions. Not applicable RESULTS: CRS-R total scores correlated with NCS-R total scores and subscores. CRS-R motor subscale correlated with NCS-R total scores and motor subscale and CRS-R oromotor subscale correlated with NCS-R total scores, as well as verbal and facial expression. There was a difference between participants with UWS and MCS in the proportion of grimace and/or crying during the noxious condition. We replicated previous findings on psychometric properties of the scale, but found a different score as the best threshold for nociception. We report a strong relationship between responsiveness to nociception and the level of consciousness. The NCS-R seems to offer a valuable tool to assess nociception in an efficient manner, but additional studies are needed to allow recommendations for clinical assessment of subjective pain experience. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  18. Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

    PubMed

    Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

    2018-03-01

    In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

  19. Noxious heat threshold temperature and pronociceptive effects of allyl isothiocyanate (mustard oil) in TRPV1 or TRPA1 gene-deleted mice.

    PubMed

    Tékus, Valéria; Horváth, Ádám; Hajna, Zsófia; Borbély, Éva; Bölcskei, Kata; Boros, Melinda; Pintér, Erika; Helyes, Zsuzsanna; Pethő, Gábor; Szolcsányi, János

    2016-06-01

    To investigate the roles of TRPV1 and TRPA1 channels in baseline and allyl isothiocyanate (AITC)-evoked nociceptive responses by comparing wild-type and gene-deficient mice. In contrast to conventional methods of thermonociception measuring reflex latencies, we used our novel methods to determine the noxious heat threshold. It was revealed that the heat threshold of the tail measured by an increasing-temperature water bath is significantly higher in TRPV1(-/-), but not TRPA1(-/-), mice compared to respective wild-types. There was no difference between the noxious heat thresholds of the hind paw as measured by an increasing-temperature hot plate in TRPV1(-/-), TRPA1(-/-) and the corresponding wild-type mice. The withdrawal latency of the tail from 0°C water was prolonged in TRPA1(-/-), but not TRPV1(-/-), mice compared to respective wild-types. In wild-type animals, dipping the tail or paw into 1% AITC induced an 8-14°C drop of the noxious heat threshold (heat allodynia) of both the tail and paw, and 40-50% drop of the mechanonociceptive threshold (mechanical allodynia) of the paw measured by dynamic plantar esthesiometry. These AITC-evoked responses were diminished in TRPV1(-/-), but not TRPA1(-/-), mice. Tail withdrawal latency to 1% AITC was significantly prolonged in both gene-deleted strains. Different heat sensors determine the noxious heat threshold in distinct areas: a pivotal role for TRPV1 on the tail is contrasted with no involvement of either TRPV1 or TRPA1 on the hind paw. Noxious heat threshold measurement appears appropriate for preclinical screening of TRP channel ligands as novel analgesics. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. MRI Evaluation of Non-Necrotic T2-Hyperintense Foci in Pediatric Diffuse Intrinsic Pontine Glioma.

    PubMed

    Clerk-Lamalice, O; Reddick, W E; Li, X; Li, Y; Edwards, A; Glass, J O; Patay, Z

    2016-05-19

    The conventional MR imaging appearance of diffuse intrinsic pontine glioma suggests intralesional histopathologic heterogeneity, and various distinct lesion components, including T2-hypointense foci, have been described. Here we report the prevalence, conventional MR imaging semiology, and advanced MR imaging features of non-necrotic T2-hyperintense foci in diffuse intrinsic pontine glioma. Twenty-five patients with diffuse intrinsic pontine gliomas were included in this study. MR imaging was performed at 3T by using conventional and advanced MR imaging sequences. Perfusion (CBV), vascular permeability (v e , K trans ), and diffusion (ADC) metrics were calculated and used to characterize non-necrotic T2-hyperintense foci in comparison with other lesion components, namely necrotic T2-hyperintense foci, T2-hypointense foci, peritumoral edema, and normal brain stem. Statistical analysis was performed by using Kruskal-Wallis and Wilcoxon rank sum tests. Sixteen non-necrotic T2-hyperintense foci were found in 12 tumors. In these foci, ADC values were significantly higher than those in either T2-hypointense foci (P = .002) or normal parenchyma (P = .0002), and relative CBV values were significantly lower than those in either T2-hypointense (P = .0002) or necrotic T2-hyperintense (P = .006) foci. Volume transfer coefficient values in T2-hyperintense foci were lower than those in T2-hypointense (P = .0005) or necrotic T2-hyperintense (P = .0348) foci. Non-necrotic T2-hyperintense foci are common, distinct lesion components within diffuse intrinsic pontine gliomas. Advanced MR imaging data suggest low cellularity and an early stage of angioneogenesis with leaky vessels resulting in expansion of the extracellular space. Because of the lack of biopsy validation, the underlying histoarchitectural and pathophysiologic changes remain unclear; therefore, these foci may correspond to a poorly understood biologic event in tumor evolution. © 2016 American Society of Neuroradiology.

  1. 7 CFR 301.1 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

  2. 7 CFR 301.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... articles, means of conveyance, plants, plant products, biological control organisms, plant pests, or... biological control organism, plant pest, or noxious weed within the United States. The only exceptions to..., plant products, biological control organisms, plant pests, or noxious weeds that are in addition to the...

  3. 33 CFR 151.39 - Operating requirements: Category D NLS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  4. 33 CFR 151.39 - Operating requirements: Category D NLS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  5. 33 CFR 151.43 - Control of discharge of NLS residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  6. 33 CFR 151.43 - Control of discharge of NLS residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  7. 33 CFR 151.43 - Control of discharge of NLS residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  8. 33 CFR 151.43 - Control of discharge of NLS residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  9. 33 CFR 151.39 - Operating requirements: Category D NLS.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  10. 33 CFR 151.39 - Operating requirements: Category D NLS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  11. 33 CFR 151.39 - Operating requirements: Category D NLS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  12. 33 CFR 151.43 - Control of discharge of NLS residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  13. A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

    PubMed

    Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

    2017-08-01

    Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

  14. [Occupational digestive diseases in chemical industry workers of West Siberia].

    PubMed

    Pomytkina, T E; Pershin, A N

    2010-01-01

    The high incidence of chronic digestive diseases is recorded in chemical industry workers exposed to the isolated action of noxious substances. The aim of the investigation was to make a hygienic assessment of the risk for occupational digestive diseases in chemical industry workers exposed to a combination of noxious drugs. The working conditions and the prevalence of digestive diseases were studied in 4120 workers engaged in chemical and auxiliary processes. Under the isolated action of noxious substances, the workers had an average of 35% increase in the incidence of digestive diseases than unexposed ones (p < 0.05). Under the combined action of hazardous substances, the incidence of digestive diseases was 1.7-fold greater (p < 0.05) than in the unexposed subjects and 1.2-fold greater in those under isolated action. The odd ratio and relative risk for digestive diseases in the workers exposed to a combination of noxious substances were 4.0-11.1 and 3.5-10.7 times higher, respectively (p < 0.05) than in the unexposed subjects.

  15. Suppression of bulboreticular unit responses to noxious stimuli by analgesic mesencephalic stimulation.

    PubMed

    Morrow, T J; Casey, K L

    1983-01-01

    The responses of 302 neurons in the medial medullary reticular formation (MRF) to a variety of noxious and innocuous somatic stimuli were studied in anesthetized and awake rats. In addition, the effects of analgesic electrical stimulation in the mesencephalon (MES) on unit responses were examined. Tail shock was the most effective stimulus, exciting more than 80% of all units recorded. This stimulus was considered separately during data analysis, since it could not be classified as noxious or innocuous. Noxious somatic stimuli (including pinch, firm pressure, pin prick, and radiant heating of the tail above 45 degrees C were especially effective in eliciting discharge in a significant fraction of all cells in both awake (123/205) and anesthetized (45/97) animals. Nociceptive neurons could be classified as nociceptive specific (NS) or wide dynamic range (WDR) depending on their responses to all somatic stimuli tested. Nociceptive neurons showed no preferential anatomical distribution. Most neurons, including those responsive to noxious inputs, exhibited large, often bilateral receptive fields which frequently covered the tail, one or more limbs, and extensive areas of the body or head. Electrical stimulation within or adjacent to the mesencephalic periaqueductal gray matter depressed the spontaneous and evoked discharge of MRF neurons in both acute and chronic preparations. This inhibition showed a significant preference (p less than 0.001, chi-square statistic) for units that were excited by somatic and especially noxious stimuli. No units were facilitated by MES stimulation. In the awake rat, unit suppression closely followed the time course and level of MES-induced analgesia. Excitability data from the acute experiments suggest that this response inhibition may be the result of a direct action on MRF neurons. Anesthesia severely depressed the spontaneous discharge of MRF neurons as well as the activity evoked by innocuous somatic stimulation. Our data suggest that analgesia produced by MES stimulation is at least in part due to the depression of MRF unit activity, and support the hypothesis that MRF neurons play a critical role in the mediation of behavioral responses to noxious stimuli.

  16. ThermoTRPs and Pain

    PubMed Central

    Laing, Robyn J; Dhaka, Ajay

    2015-01-01

    The ability of the body to perceive noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors. The molecular receptors of noxious mechanical, temperature or chemical stimuli are expressed in these neurons and have drawn considerable attention as possible targets for analgesic development to improve treatment for the millions who suffer from chronic pain conditions. A number of thermoTRPs, a subset of the transient receptor potential family of ion channels, are activated by a wide range on noxious stimuli. In this review, we review the function of these channels and examine the evidence that thermoTRPs play a vital role in acute, inflammatory and neuropathic nociception. PMID:25608689

  17. 33 CFR 151.32 - Special areas for the purpose of Annex II.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  18. 7 CFR 201.16 - Noxious-weed seeds.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

  19. 7 CFR 201.52 - Noxious-weed seeds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

  20. 7 CFR 201.52 - Noxious-weed seeds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

  1. 7 CFR 201.52 - Noxious-weed seeds.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

  2. 7 CFR 201.16 - Noxious-weed seeds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

  3. 7 CFR 201.16 - Noxious-weed seeds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

  4. 7 CFR 201.16 - Noxious-weed seeds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds. 201.16 Section 201.16 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Labeling Agricultural Seeds §...

  5. 7 CFR 201.52 - Noxious-weed seeds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds. 201.52 Section 201.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS Purity Analysis in the...

  6. 33 CFR 151.32 - Special areas for the purpose of Annex II.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  7. 33 CFR 151.32 - Special areas for the purpose of Annex II.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  8. 33 CFR 151.32 - Special areas for the purpose of Annex II.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  9. 75 FR 23151 - Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-03

    .... APHIS-2008-0097] Noxious Weeds; Old World Climbing Fern and Maidenhair Creeper AGENCY: Animal and Plant... adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown) and maidenhair creeper... amended the regulations by adding Old World climbing fern (Lygodium microphyllum (Cavanilles) R. Brown...

  10. 33 CFR 151.32 - Special areas for the purpose of Annex II.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution...

  11. Meiotic recombination and spermatogenic impairment in Mus musculus domesticus carrying multiple simple Robertsonian translocations.

    PubMed

    Merico, V; Pigozzi, M I; Esposito, A; Merani, M S; Garagna, S

    2003-01-01

    We quantitatively analyzed the spermatogenic process, including evaluation of seminiferous tubules with defective cycles, rates of germ cell death and sperm morphology, in adult male mice with standard telocentric chromosomes (2n = 40, CD1 strain), homozygous (2n = 24, Mil II population) and heterozygous (2n = 24 x 40) for Robertsonian (Rb) rearrangements. The animals were analyzed at three different ages: three, five and seven months after birth. The number and position of crossover events were also determined by chiasmata counting and immunostaining with an antibody against mouse MLH1 protein. Our analysis of spermatogenesis confirms the impairment of the spermatogenic process in multiple simple heterozygotes due to both germ cell and abnormal sperm morphology. The detrimental effects exerted by Rb heterozygosities were found to be at least partially buffered with time: the frequency of defective tubules was lower and germ cell survival and sperm morphology better in 7-month-old animals than in the 3- and 5-month-old mice. While there are previously published data on germ cell death in multiple simple heterozygotes, this is the first report of a partial rescue of spermatogenesis with time. The mean frequency of MLH1 foci was lower in Rb homozygous and heterozygous mice than in mice carrying all telocentric chromosomes. The lower number of foci in Rb mice can be ascribed to a decrease in the number of multiple chiasmata and the maintenance of single chiasmata preferentially located in the terminal region of both the telocentric and metacentric chromosomes. Copyright 2003 S. Karger AG, Basel

  12. Reassignment of scattered emission photons in multifocal multiphoton microscopy.

    PubMed

    Cha, Jae Won; Singh, Vijay Raj; Kim, Ki Hean; Subramanian, Jaichandar; Peng, Qiwen; Yu, Hanry; Nedivi, Elly; So, Peter T C

    2014-06-05

    Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.

  13. On-axis non-linear effects with programmable Dammann lenses under femtosecond illumination.

    PubMed

    Pérez Vizcaíno, Jorge; Mendoza-Yero, Omel; Borrego-Varillas, Rocío; Mínguez-Vega, Gladys; Vázquez de Aldana, Javier R; Láncis, Jesús

    2013-05-15

    We demonstrate the utilization of Dammann lenses codified onto a spatial light modulator (SLM) for triggering non-linear effects. With continuous wave illumination Dammann lenses are binary phase optical elements that generate a set of equal intensity foci. We theoretically calculate the influence of ultrashort pulse illumination on the uniformity of the generated pattern, which is affected by chromatic aberration for pulses with temporal widths lower than 100 fs. The simulations also indicate that acceptable uniformity can be achieved for pulses of several fs by shortening the distance among foci which can be easily modified with the SLM. Multifocal second-harmonic generation (SHG) and on-axis multiple filamentation are produced and actively controlled in β-BaB2O4 (BBO) and fused silica samples, respectively, with an amplified Ti: Sapphire femtosecond laser of 30 fs pulse duration. Experimental results are in very good agreement with theoretical calculations.

  14. Poly(A)-binding proteins and mRNA localization: who rules the roost?

    PubMed

    Gray, Nicola K; Hrabálková, Lenka; Scanlon, Jessica P; Smith, Richard W P

    2015-12-01

    RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals. © 2015 Authors; published by Portland Press Limited.

  15. γH2AX foci on apparently intact mitotic chromosomes: Not signatures of misrejoining events but signals of unresolved DNA damage

    PubMed Central

    Martín, Marta; Terradas, Mariona; Hernández, Laia; Genescà, Anna

    2014-01-01

    The presence of γH2AX foci on apparently intact mitotic chromosomes is controversial because they challenge the assumed relationship between γH2AX foci and DNA double-strand breaks (DSBs). In this work, we show that after irradiation during interphase, a variety of γH2AX foci are scored in mitotic cells. Surprisingly, approximately 80% of the γH2AX foci spread over apparently undamaged chromatin at Terminal or Interstitial positions and they can display variable sizes, thus being classified as Small, Medium and Big foci. Chromosome and chromatid breaks that reach mitosis are spotted with Big (60%) and Medium (30%) Terminal γH2AX foci, but very rarely are they signaled with Small γH2AX foci. To evaluate if Interstitial γH2AX foci might be signatures of misrejoining, an mFISH analysis was performed on the same slides. The results show that Interstitial γH2AX foci lying on apparently intact chromatin do not mark sites of misrejoining, and that misrejoined events were never signaled by a γH2AX foci during mitosis. Finally, when analyzing the presence of other DNA-damage response (DDR) factors we found that all γH2AX foci—regardless their coincidence with a visible break—always colocalized with MRE11, but not with 53BP1. This pattern suggests that these γH2AX foci may be hallmarks of both microscopically visible and invisible DNA damage, in which an active, although incomplete or halted DDR is taking place. PMID:25486563

  16. All atypia diagnosed at stereotactic vacuum-assisted breast biopsy do not need surgical excision.

    PubMed

    de Mascarel, Isabelle; Brouste, Véronique; Asad-Syed, Maryam; Hurtevent, Gabrielle; Macgrogan, Gaëtan

    2011-09-01

    The necessity of excision is debatable when atypia are diagnosed at stereotactic vacuum-assisted breast biopsy (microbiopsy). Among the 287 surgical excisions performed at Institut Bergonié from 1999 to 2009, we selected a case-control study group of 151 excisions; 52 involving all the diagnosed cancers and 99 randomly selected among the 235 excisions without cancer, following atypical microbiopsy (24 flat epithelial atypia; 50 atypical ductal hyperplasia; 14 lobular neoplasia; 63 mixed lesions). Mammographical calcification (type, extension, complete removal) and histological criteria of epithelial atypia (type, number of foci, size/extension), topography and microcalcification extension at microbiopsy were compared according to the presence or absence of cancer at excision. Factors associated with cancer at excision were Breast Imaging Reporting and Data System (BI-RADS5) lesions, large and/or multiple foci of mammographical calcifications, histological type, number, size and extension of atypical foci. Flat epithelial atypia alone was never associated with cancer at excision. BI-RADS5, atypical ductal hyperplasia (alone or predominant) and >3 foci of atypia were identified as independent pejorative factors. There was never any cancer at excision when these pejorative factors were absent (n=31). Presence of one (n=59), two (n=23) or three (n=14) factors was associated with cancer in 24, 15 and 13 cases with an odds ratio=5.8 (95% CI: 3-11.2) for each additional factor. We recommend that mammographical data and histological characteristics be taken into account in the decision-making process after diagnosis of atypia on microbiopsy. With experienced senologists and strict histological criteria, some patients could be spared surgery resulting in significant patient, financial and time advantages.

  17. Simultaneous Biatrial High-Density (510-512 Electrodes) Epicardial Mapping of Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: New Insights Into the Mechanism of Its Maintenance.

    PubMed

    Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Cakulev, Ivan; Markowitz, Alan; Waldo, Albert L

    2015-12-01

    The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation. Twelve patients with persistent and LSP AF (1 month to 9 years duration) were studied at open heart surgery. During AF, electrograms were recorded from both atria simultaneously for 1 to 5 minutes from 510 to 512 epicardial electrodes with ECG lead II. Thirty-two consecutive seconds of activation sequence maps were produced per patient. During AF, multiple foci (QS unipolar atrial electrograms) of different cycle lengths (mean, 175 ± 18 ms) were present in both atria in 11 of 12 patients. Foci (2-4 per patient, duration 5-32 s) were either sustained or intermittent, were predominantly found in the lateral left atrial free wall, and likely acted as drivers. Random and nonrandom breakthrough activation sites (initial r or R in unipolar atrial electrograms) were also found. In 1 of 12 patients, only breakthrough sites were found. All wave fronts emanated from foci and breakthrough sites, and largely either collided or merged with each other at variable sites. Repetitive focal QS activation occasionally generated repetitive wannabe reentrant activation in 5 of 12 patients. No actual reentry was found. During persistent and LSP AF in 12 patients, wave fronts emanating from foci and breakthrough sites maintained AF. No reentry was demonstrated. © 2015 American Heart Association, Inc.

  18. History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation.

    PubMed

    Wongcharoen, Wanwarang; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Chong, Eric; Chao, Tze-Fan; Tuan, Ta-Chuan; Chang, Yao-Ting; Lin, Chin-Yu; Liao, Jo-Nan; Lin, Yi-Chun; Chen, Yun-Yu; Chen, Shih-Ann

    2015-09-01

    Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status. The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism. The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients. Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P < .01), and higher prevalence of non-PV foci (42% vs 23%, P < .01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P < .01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history. Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  19. 7 CFR 361.6 - Noxious weed seeds.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Noxious weed seeds. 361.6 Section 361.6 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... measured from the base of the rachilla. (3) Seeds of legumes (Fabaceae) with the seed coats entirely...

  20. 7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  1. 7 CFR 201.65 - Noxious weed seeds in interstate commerce.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  2. 7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  3. 7 CFR 201.65 - Noxious-weed seeds in interstate commerce.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  4. 7 CFR 201.65 - Noxious weed seeds in interstate commerce.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious weed seeds in interstate commerce. 201.65 Section 201.65 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  5. 7 CFR 352.2 - Purpose; relation to other regulations; applicability; preemption of State and local laws.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... article, means of conveyance, plant, biological control organism, plant pest, noxious weed, or plant... prevent the introduction or dissemination of a biological control organism, plant pest, or noxious weed...) The provisions in this part apply whether the controls over arrival, temporary stay, unloading...

  6. 43 CFR 4120.5-2 - Cooperation with Tribal, state, county, and Federal agencies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... laws and regulations relating to livestock, livestock diseases, sanitation, and noxious weeds... 1971 (16 U.S.C. 1331 et seq.); (b) County or other local weed control districts in analyzing noxious weed problems and developing control programs for areas of the public lands and other lands...

  7. 7 CFR 623.13 - Wetlands reserve plan of operations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

  8. 7 CFR 623.13 - Wetlands reserve plan of operations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... program, including, but not limited to: (i) Measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) Measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

  9. 7 CFR 623.13 - Wetlands reserve plan of operations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... program, including, but not limited to: (i) measures to control noxious weeds and insect pests in order to comply with applicable Federal, or State noxious weed and pest control laws; and (ii) measures to control other specified species of weeds, insects or pests; (3) Specify compatible land uses for personal...

  10. 33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  11. 33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  12. 33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  13. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  14. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  15. 33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  16. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  17. 33 CFR 151.49 - Category C and D Oil-like NLSs allowed for carriage.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  18. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  19. A field guide for forest indicator plants, sensitive plants, and noxious weeds of the Shoshone National Forest, Wyoming

    Treesearch

    Kent E. Houston; Walter J. Hartung; Carol J. Hartung

    2001-01-01

    This field guide was designed for people with minimal botanical training. It is an identification aid to plant species that have ecological indicator value, are on sensitive species lists, or are considered noxious weeds. It contains illustrations and simplified taxonomic descriptions.

  20. [Mechanisms for the formation of a combination of the natural foci of trematodiases and tularemia in the floodplain-river ecosystem of the Konda River in different periods of epizootic activity of an infection focus].

    PubMed

    Ushakov, A V

    2011-01-01

    The basis of the mechanism responsible for the formation of a combination of the natural foci of trematodiases and tularemia in the infection foci in the interepizootic periods is their association with the morphological structure of the floodplain-river landscape of the Konda River. The landscape's facias and holes, which are common to the foci, are integrated, by predetermining the territorial combination. The formation of a closed trinomial Francisella tularensis parasite system integrating these foci serves as a basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia on transition of the latter from the interepizootic state to epizooty. The absence of host populations linking the foci of methorchiasis (M. xanthosomus), bilharziasis, and tularemia determines their combination both in the interepizootic periods and at the level of the landscape morphological structure. The basis for the mechanism of the formation of a combination of the natural foci of trematodiases and tularemia in the periods of diffuse epizooties in the infection foci is the formation of an open binomial F. tularensis parasite system and the infestation of the co-members of F. tularensis trematode parasite systems. By penetrating into them, the pathogen forces the F. tularensis parasite system to enter the trematode parasite systems, causing their complete (opisthorchiases, methorchiases) or partial (bilharziasis) coincidence. Thus, these foci are combined at the level of parasitocenoses of the parasite systems of infections and infestations, by giving rise to pseudosystem combined foci. The natural foci of B. polonica and F. tularensis are combined at the level of parasitocenosis of the coacting hemipopulation of trematode parthenitas, F. tularensis subpopulations and intermediate host population, by forming an autoecious population-combination bilharziasis-tularemia focus. The formation of territorial-combination, autoecious population-combination, and pseudosystem-combination foci of trematodiases and tularemia in different periods of the epizootic activity of an infection focus is determined by the functional organization of the parasite system of a tularemia focus and the biocenotic (functional) structure of natural foci of infestations.

  1. A Protocol Analysis of the Influence of Technology on Students' Actions, Verbal Commentary, and Thought Processes During the Performance of Acid-Base Titrations.

    ERIC Educational Resources Information Center

    Nakhleh, Mary B.; Krajcik, Joseph S.

    1993-01-01

    From an analysis of 14 secondary student's actions and thought processes, it was found that technology's level of information affected the focus of student observations. The microcomputer group focused primarily on the graph while other groups exhibited multiple foci. The discussion data also reveal that students have three main ideas about how…

  2. Mapping transmission foci to eliminate malaria in the People's Republic of China, 2010-2015: a retrospective analysis.

    PubMed

    Feng, Jun; Tu, Hong; Zhang, Li; Zhang, Shaosen; Jiang, Shan; Xia, Zhigui; Zhou, Shuisen

    2018-03-07

    China has initiated the National Malaria Elimination Action Plan, which aims to eliminate malaria by 2020. However, the transmission of malaria occurs sporadically or in distinct foci, which greatly hampers progress toward elimination in China and other countries. The object of this study was to foci categorization and evaluates whether the response met the requirements issued by the nation or WHO. Residual transmissions were investigated and located with fine spatial resolution mapping from parasitological confirmed malaria cases by use of routine national surveillance data. The "1-3-7" timeframes were monitored for each focus between 2012 and 2015. Each focus was identified, and the application of appropriate measures was evaluated. A total of 5996 indigenous cases were recorded between 2010 and 2015; during this period, the number of cases declined by 99.1% (2010, n = 4262; 2015, n = 39). Most indigenous cases (92.5%) were reported in Anhui (n = 2326), Yunnan (n = 1373), Henan (n = 930), Hubei (n = 459), and Guizhou (n = 458). The temporal distribution showed that the indigenous malaria cases were clustered during the period of May to August. A total of 320 foci were carefully investigated and analyzed: 24 were active foci; 72, residual non-active foci; and 224 cleared-up foci. For the foci response evaluation, all the active foci were investigated within 7 days, while 80.2% of the residual non-active foci were responded within 7 days. In addition, reactive case detection (RACD) was carried out with 92.9% of the active foci and vector investigation carried out with 75%. For residual non-active foci, RACD was carried out with 83.2% and vector investigation with 78.2% of the foci. This study used nationwide data to categorize foci in China and evaluate the response of these areas during the control and elimination phases. Our approach stratifies future control responses by identifying those locations where the elimination of endemic transmission is needed, such as in the counties at the China-Myanmar border and in Tibet. In addition, this study will help local CDC staff to reassess their needs and responses against different types of foci during the elimination and post-elimination phases.

  3. The Analysis of the Patterns of Radiation-Induced DNA Damage Foci by a Stochastic Monte Carlo Model of DNA Double Strand Breaks Induction by Heavy Ions and Image Segmentation Software

    NASA Technical Reports Server (NTRS)

    Ponomarev, Artem; Cucinotta, F.

    2011-01-01

    To create a generalized mechanistic model of DNA damage in human cells that will generate analytical and image data corresponding to experimentally observed DNA damage foci and will help to improve the experimental foci yields by simulating spatial foci patterns and resolving problems with quantitative image analysis. Material and Methods: The analysis of patterns of RIFs (radiation-induced foci) produced by low- and high-LET (linear energy transfer) radiation was conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Some data analysis was done with the help of image segmentation software that identifies individual classes of RIFs and colocolized RIFs, which is of importance to some experimental assays that assign DNA damage a dual phosphorescent signal. Results: The model predicts the spatial and genomic distributions of DNA DSBs (double strand breaks) and associated RIFs in a human cell nucleus for a particular dose of either low- or high-LET radiation. We used the model to do analyses for different irradiation scenarios. In the beam-parallel-to-the-disk-of-a-flattened-nucleus scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular-beam scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. In another analysis, our image segmentaiton software determined foci yields directly from images with single-class or colocolized foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantization of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiments using proteins that detect DNA damage. An automated image segmentaiton software can prove useful in a faster and more precise object counting for colocolized foci images.

  4. [The results of serological studies in different foci of tropical and tertiary malaria].

    PubMed

    Suleĭmanov, G D; Doan, Kh N; Le, T T; Chan, B; Chan, T U

    1991-01-01

    Attempt was made to determine the value of serologic indices of malaria surveys. Following uniformed methodological and technical approaches 3 foci of P. vivax and 6 foci of P. falciparum malaria were surveyed in different endemic zones of Vietnam and the USSR. It was shown that the most objective criteria for a foci classification is its serologic mean geometric titre. The latter in its turn directly depends of transmission longevity in a foci.

  5. [Correlative factors related to the density of Meriones unguiculatus in the Meriones unguiculatus plague foci of Hebei province, 2001-2013].

    PubMed

    Niu, Y F; Kang, X P; Yan, D; Zhang, Y H; Liu, G; Kang, D M; Liu, H Z; Shi, X M; Li, Y G

    2016-08-10

    To explore the yearly, monthly and habitat-related distribution and their relations with Meriones unguiculatus density in the Hebei Meriones unguiculatus plague foci, from 2001 to 2013. Data related to Meriones unguiculatus was gathered through the monitoring programs set up at the national and provincial Meriones unguiculatus plague foci in Hebei province, from 2001 to 2013. According to the yearly density of Meriones unguiculatus, criteria set for the three groups under study, were as follows:'high-risk group'-when the rodent density was≥1.00 under rodents/hm(2),'warning group'-when the rodents/hm(2)>rodent density> 0.20,'standard group'-when rodents/hm(2) rodent density≤0.20 rodents/hm(2). Differences of habitats and monthly distribution among the three groups were compared, under the Kruskal-Wallis H rank sum test while their relations were under the multiple correspondence analysis. The Meriones unguiculatus densities were higher than 1.00 rodents/hm(2), far above the set national standards, in the monitoring area, between 2001 and 2005. From 2005, though the rodent densities began to decrease, however, figures from 2008 to 2013 were still among 0.20 to 1.00 rodents/hm(2). The distribution of habitats in the three groups showed that the Meriones unguiculatus densities were all different in habitats and the difference was statistically significant (P<0.05). The highest median densities were all in the arable land, with maximum value of high-risk group appeared the highest (20.50 rodents/hm(2)) in the wasteland. Monthly distribution showed that the Meriones unguiculatus densities were different and the difference was statistically significant (P<0.05) in the high-risk and standard groups but not statistically significant in the warning group. Data from the multiple correspondence analysis showed that there was a strong aggregation among wasteland, in April and June, while the warning group was associated with weather in July and the arable land. When the density became higher than 1.00 rodents/hm(2), the risk on animal plague increased in Hebei Meriones unguiculatus plague foci. Based on the distribution of Meriones unguiculatus, programs should be set to monitor the rodent in arable land and wasteland, in April and June, to reduce the prevalence of animals plague.

  6. Early Sonographic Diagnosis of Neurocutaneous Melanosis in a Newborn

    PubMed Central

    Yakut, Zeynep Ilerisoy; Bas, Ahmet Yagmur; Turan, Aynur; Demirel, Nihal; Demirkan, Tulin Hakan

    2014-01-01

    Neurocutaneous melanosis (NCM) is a rare, congenital non-hereditary syndrome, characterized by multiple pigmented nevi. We report the radiologic findings of a newborn who had extensive cutaneous melanotic nevus with satellite lesions in the brain. Ultrasound showed multiple echogenic foci in the cerebral parenchyma. Subsequent MRI confirmed these lesions as characteristic deposits of melanin. The infant was asymptomatic, but presence of risk factors such as malign transformation or neurological manifestations makes early diagnosis very important. We present this case to emphasize on the radiological findings of this syndrome in order to reach an early diagnosis. PMID:25780540

  7. Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation.

    PubMed

    Yoshikawa, Y; Yamasaki, A; Takatori, K; Suzuki, M; Kobayashi, J; Takao, M; Zhang-Akiyama, Q-M

    2015-10-01

    Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in Escherichia coli (E. coli) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H2O2), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H2O2. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH(•), and H2O2, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H2O2 induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.

  8. The Effects of Noxious Subliminal Suggestion upon Smoking Attitudes and Behavior.

    ERIC Educational Resources Information Center

    Dutto, Franklin N.; Galli, Nicholas

    The efforts of smoking cessation programs have met with various degrees of success and fresh approaches to the problem are needed. An innovative technique that interrupts the psychogenic drives of smokers was employed to determine the effect of noxious subliminal suggestion on smoking attitudes and behavior. Adult smokers (N=60) were shown…

  9. 33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.35 Certificates needed to carry Category D NLS and Category D Oil-like... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID...

  10. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance Pollution § 151.33 Certificates needed to carry Category C Oil-like NLS. (a) A U.S. oceangoing ship may not... HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL...

  11. 7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 3 2013-01-01 2013-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  12. 7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 3 2014-01-01 2014-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  13. 7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 3 2011-01-01 2011-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  14. 7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  15. 7 CFR 201.17 - Noxious-weed seeds in the District of Columbia.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 3 2012-01-01 2012-01-01 false Noxious-weed seeds in the District of Columbia. 201.17 Section 201.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) FEDERAL SEED ACT FEDERAL SEED ACT REGULATIONS...

  16. 75 FR 1655 - Proposed Information Collection Request Submitted for Public Comment and Recommendations...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-12

    ... provide a safe environment for miners. Methane is liberated from the strata, and noxious gases and dusts from blasting and other mining activities may be present. The explosive and noxious gases and dusts... collection of information, including the validity of the methodology and assumptions used; Enhance the...

  17. 76 FR 43706 - Final Supplementary Rules To Require the Use of Certified Noxious-Weed-Free Forage and Straw on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... to use certified noxious-weed-free forage and straw. Restoration, rehabilitation, and stabilization... domestic ungulates, weaken rehabilitation and landscape restoration efforts, increase soil erosion and... consistent with and supportive of the statewide Conservation Plan for the Greater Sage- Grouse in Idaho...

  18. 33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

  19. 33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

  20. 33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

  1. 33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

  2. 33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

  3. 33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

  4. 33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

  5. 33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

  6. 33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

  7. 33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

  8. 33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

  9. 33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

  10. 33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

  11. 33 CFR 151.37 - Obtaining an Attachment for NLSs to the IOPP Certificate and obtaining an NLS Certificate.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.37 Obtaining an Attachment for NLSs to the...

  12. 33 CFR 151.41 - Operating requirements for oceangoing ships with IOPP Certificates: Category C and D Oil-like NLSs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.41 Operating requirements for oceangoing ships...

  13. 33 CFR 151.31 - Where to find requirements applying to oceangoing ships carrying Category A, B, C, and D NLS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of... Pollution from Ships Noxious Liquid Substance Pollution § 151.31 Where to find requirements applying to...

  14. 33 CFR 151.35 - Certificates needed to carry Category D NLS and Category D Oil-like NLS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) POLLUTION VESSELS CARRYING OIL, NOXIOUS LIQUID SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Implementation of MARPOL 73/78 and the Protocol on Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious...

  15. Final Environmental Assessment for Expanding the North Military Operations in Urban Terrain (MOUT) Target Array at Avon Park Air Force Range, Florida

    DTIC Science & Technology

    2005-01-01

    native groundcover vegetation. Specifically, natalgrass (Rhynchelytrum repens) and Cogan grass ( Imperata cylindrica ), both invasive exotics, have the...stability creates an environment conducive for noxious weeds. If noxious weeds establish, the EA acknowledges that they can be chemically treated

  16. Fear appeals and attitude change: effects of a threat's noxiousness, probability of occurrence, and the efficacy of coping responses.

    PubMed

    Rogers, R W; Mewborn, C R

    1976-07-01

    Three factorial experiments examined the persuasive effects of the noxiousness of threatened event, its probability of occurrence, and the efficacy of recommended protective measures. A total of 176 students participated in separate studies on the topics of cigarette smoking, driving safety, and venereal disease. The results disclosed that increments in the efficacy variable increased intentions to adopt the efficacy variable increased intentions to adopt the recommended practices. Interaction effects revealed that when the preventive practices were effective, increments in the noxiousness and probability variables facilitated attitude change; however, when the coping responses were the preventive practices were effective, increments in the noxiousness and probability either had no effect or a deleterious effect, respectively. These interaction effects were discussed in terms of a defensive avoidance hypothesis, the crucial component of which was an inability to ward off the danger. Furthermore, the effect of the emotion of fear upon intentions was found to be mediated by the cognitive appraisal of severity of the threat. Finally, similarities with and extensions of previous studies were reviewed.

  17. Coexistence of Multiple Attractors in an Active Diode Pair Based Chua’s Circuit

    NASA Astrophysics Data System (ADS)

    Bao, Bocheng; Wu, Huagan; Xu, Li; Chen, Mo; Hu, Wen

    This paper focuses on the coexistence of multiple attractors in an active diode pair based Chua’s circuit with smooth nonlinearity. With dimensionless equations, dynamical properties, including boundness of system orbits and stability distributions of two nonzero equilibrium points, are investigated, and complex coexisting behaviors of multiple kinds of disconnected attractors of stable point attractors, limit cycles and chaotic attractors are numerically revealed. The results show that unlike the classical Chua’s circuit, the proposed circuit has two stable nonzero node-foci for the specified circuit parameters, thereby resulting in the emergence of multistability phenomenon. Based on two general impedance converters, the active diode pair based Chua’s circuit with an adjustable inductor and an adjustable capacitor is made in hardware, from which coexisting multiple attractors are conveniently captured.

  18. Effects of propofol anesthesia on the processing of noxious stimuli in the spinal cord and the brain.

    PubMed

    Lichtner, Gregor; Auksztulewicz, Ryszard; Kirilina, Evgeniya; Velten, Helena; Mavrodis, Dionysios; Scheel, Michael; Blankenburg, Felix; von Dincklage, Falk

    2018-05-15

    Drug-induced unconsciousness is an essential component of general anesthesia, commonly attributed to attenuation of higher-order processing of external stimuli and a resulting loss of information integration capabilities of the brain. In this study, we investigated how the hypnotic drug propofol at doses comparable to those in clinical practice influences the processing of somatosensory stimuli in the spinal cord and in primary and higher-order cortices. Using nociceptive reflexes, somatosensory evoked potentials and functional magnet resonance imaging (fMRI), we found that propofol abolishes the processing of innocuous and moderate noxious stimuli at low to medium concentration levels, but that intense noxious stimuli evoked spinal and cerebral responses even during deep propofol anesthesia that caused profound electroencephalogram (EEG) burst suppression. While nociceptive reflexes and somatosensory potentials were affected only in a minor way by further increasing doses of propofol after the loss of consciousness, fMRI showed that increasing propofol concentration abolished processing of intense noxious stimuli in the insula and secondary somatosensory cortex and vastly increased processing in the frontal cortex. As the fMRI functional connectivity showed congruent changes with increasing doses of propofol - namely the temporal brain areas decreasing their connectivity with the bilateral pre-/postcentral gyri and the supplementary motor area, while connectivity of the latter with frontal areas is increased - we conclude that the changes in processing of noxious stimuli during propofol anesthesia might be related to changes in functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Reduced local field potential power in the medial prefrontal cortex by noxious stimuli.

    PubMed

    Li, Ai-Ling; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo

    2016-10-01

    Nociceptive signals produced by noxious stimuli at the periphery reach the brain through ascending pathways. These signals are processed by various brain areas and lead to activity changes in those areas. The medial prefrontal cortex (mPFC) is involved in higher cognitive functions and emotional processing. It receives projections from brain areas involved in nociception. In this study, we investigated how nociceptive input from the periphery changes the local field potential (LFP) activity in the mPFC. Three different types of noxious stimuli were applied to the hind paw contralateral to the LFP recording site. They were transcutaneous electrical stimulations, mechanical stimuli and a chemical stimulus (formalin injection). High intensity transcutaneous stimulations (10V to 50V) and noxious mechanical stimulus (pinch) significantly reduced the LFP power during the stimulating period (p<0.05), but not the low intensity subcutaneous stimulations (0.1V to 5V) and other innocuous mechanical stimuli (brush and pressure). More frequency bands were inhibited with increased intensity of transcutaneous electrical stimulation, and almost all frequency bands were inhibited by stimulations at or higher than 30v. Pinch significantly reduced the power for beta band and formalin injection significantly reduced the power of alpha and beta band. Our data demonstrated the noxious stimuli-induced reduction of LFP power in the mPFC, which indicates the active processing of nociceptive information by the mPFC. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The visceromotor responses to colorectal distension and skin pinch are inhibited by simultaneous jejunal distension.

    PubMed

    Shafton, Anthony D; Furness, John B; Ferens, Dorota; Bogeski, Goce; Koh, Shir Lin; Lean, Nicholas P; Kitchener, Peter D

    2006-07-01

    Noxious stimuli that are applied to different somatic sites interact; often one stimulus diminishes the sensation elicited from another site. By contrast, inhibitory interactions between visceral stimuli are not well documented. We investigated the interaction between the effects of noxious distension of the colorectum and noxious stimuli applied to the jejunum, in the rat. Colorectal distension elicited a visceromotor reflex, which was quantified using electromyographic (EMG) recordings from the external oblique muscle of the upper abdomen. The same motor units were activated when a strong pinch was applied to the flank skin. Distension of the jejunum did not provoke an EMG response at this site, but when it was applied during colorectal distension it blocked the EMG response. Jejunal distension also inhibited the response to noxious skin pinch. The inhibition of the visceromotor response to colorectal distension was prevented by local application of tetrodotoxin to the jejunum, and was markedly reduced when nicardipine was infused into the local jejunal circulation. Chronic sub-diaphragmatic vagotomy had no effect on the colorectal distension-induced EMG activity or its inhibition by jejunal distension. The nicotinic antagonist hexamethonium suppressed phasic contractile activity in the jejunum, had only a small effect on the inhibition of visceromotor response by jejunal distension. It is concluded that signals that arise from skin pinch and colorectal distension converge in the central nervous system with pathways that are activated by jejunal spinal afferents; the jejunal signals strongly inhibit the abdominal motor activity evoked by noxious stimuli.

  1. In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle.

    PubMed

    Pohl, M; Collin, E; Bourgoin, S; Clot, A M; Hamon, M; Cesselin, F; Le Bars, D

    1992-10-01

    The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.

  2. Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.

    PubMed

    Vandersickel, Veerle; Beukes, Philip; Van Bockstaele, Bram; Depuydt, Julie; Vral, Anne; Slabbert, Jacobus

    2014-02-01

    To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.

  3. Tumor suppression effects of bilberry extracts and enzymatically modified isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl butoxide promotion in a two-stage rat hepatocarcinogenesis model.

    PubMed

    Hara, Shintaro; Morita, Reiko; Ogawa, Takashi; Segawa, Risa; Takimoto, Norifumi; Suzuki, Kazuhiko; Hamadate, Naobumi; Hayashi, Shim-Mo; Odachi, Ayano; Ogiwara, Isao; Shibusawa, Sakae; Yoshida, Toshinori; Shibutani, Makoto

    2014-08-01

    To investigate the protective effect of bilberry extracts (BBE) and enzymatically modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N-diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We examined the modifying effect of co-administration with BBE or EMIQ on the liver tissue environment including oxidative stress responses, cell proliferation and apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth factor (TGF)-β/Smad signalings on the induction mechanism of preneoplastic lesions during early stages of hepatocellular tumor promotion. PBO increased the numbers and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci. Co-administration of BBE or EMIQ suppressed these effects with the reductions of GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO-promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid-reactive substances to 78.4% of the PBO-promoted cases. PBO increased the incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(-) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-) foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the PBO-promoted cases. These results suggest that PBO-induced tumor promotion involves facilitation of PTEN/Akt and disruptive TGF-β/Smad signalings without relation to oxidative stress responses, but this promotion was suppressed by co-treatment with BBE or EMIQ through suppression of cell proliferation activity of preneoplastic liver cells. Copyright © 2014 Elsevier GmbH. All rights reserved.

  4. Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

    PubMed

    Vos, Fidel J; Kullberg, Bart Jan; Sturm, Patrick D; Krabbe, Paul F M; van Dijk, Arie P J; Wanten, Geert J A; Oyen, Wim J G; Bleeker-Rovers, Chantal P

    2012-03-01

    Early detection of metastatic infection in patients with Gram-positive bacteremia is important as morbidity and mortality are higher in the presence of these foci, probably due to incomplete eradication of clinically silent foci during initial treatment. We performed a prospective study in 115 patients with Staphylococcus aureus or Streptococcus species bacteremia with at least 1 risk factor for the development of metastatic foci, such as community acquisition, treatment delay, persistently positive blood cultures for >48 hours, and persistent fever >72 hours after initiation of treatment. An intensive search for metastatic infectious foci was performed including ¹⁸F-fluorodeoxyglucose-positron emission tomography in combination with low-dose computed tomography scanning for optimizing anatomical correlation (FDG-PET/CT) and echocardiography in the first 2 weeks of admission. Metastatic infectious foci were detected in 84 of 115 (73%) patients. Endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. The incidence of metastatic infection was similar in patients with Streptococcus species and patients with S. aureus bacteremia. Signs and symptoms guiding the attending physician in the diagnostic workup were present in only a minority of cases (41%). An unknown portal of entry, treatment delay >48 hours, and the presence of foreign body material were significant risk factors for developing metastatic foci. Mean C-reactive protein levels on admission were significantly higher in patients with metastatic infectious foci (74 vs. 160 mg/L). FDG-PET/CT was the first technique to localize metastatic infectious foci in 35 of 115 (30%) patients. As only a minority of foci were accompanied by guiding signs or symptoms, the number of foci revealed by symptom-guided CT, ultrasound, and magnetic resonance imaging remained low. Mortality tended to be lower in patients without complicated infection compared to those with metastatic foci (16% vs. 25%, respectively). Five of 31 patients (16%) without proven metastatic foci died. In retrospect, 3 of these 5 patients likely had metastatic foci that could not be diagnosed while alive. In patients with Gram-positive bacteremia and a high risk of developing complicated infection, a structured protocol including echocardiography and FDG-PET/CT aimed at detecting metastatic infectious foci can contribute to improved outcome.

  5. Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

    PubMed

    Williams, Monica M; Kemp, Blakelee R; Ferraro, Kenneth F; Mustillo, Sarah A

    2018-04-03

    Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, i.e. wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

  6. [Possibilities of ultrasonic investigations in differentiation of a small-foci impairment of thyroid gland].

    PubMed

    Reyti, A O; Vityuk, N V; Medvedev, V E; Starushok, I O

    2015-03-01

    The results of ultrasound investigation of microcarcinomas and nontumoral foci of thyroid gland up to 10 mm in diameter and malignant foci over 10 mm are presented. Ultrasound signs are depicted, in accordance to which a potentially malignant thyroid gland foci are delineated, what demands a morphological (cytological) verification conduction.

  7. On the black hole lens and its foci

    NASA Technical Reports Server (NTRS)

    Eshleman, Von R.; Gurrola, Eric M.; Lindal, Gunnar F.

    1989-01-01

    Methods developed for radio occultation studies of planetary atmospheres are used to predict the electromagnetic focusing properties of a refracting lens representation of a Schwarzschild black hole. The infinity of foci are of three distinct types: a principal forward axial focus which is by far the strongest; higher-order forward axial foci; and backward conical foci with axial nulls.

  8. Focusing light through strongly scattering media by controlling binary amplitude optimization using genetic algorithm

    NASA Astrophysics Data System (ADS)

    Liu, Zhipeng; Zhang, Bin; Feng, Qi; Chen, Zhaoyang; Lin, Chengyou; Ding, Yingchun

    2017-06-01

    Focusing light through strongly scattering media plays an important role in biomedical imaging and therapy. Here, we experimentally demonstrate light focusing through ZnO sample by controlling binary amplitude optimization using genetic algorithm. In the experiment, we use a Micro Electro-Mechanical System (MEMS)-based digital micromirror device (DMD) which is in amplitude-only modulation mode. The DMD consists of 1920×1080 square mirrors that can be independently controlled to reflect light to a desired position. We control only 160 thousand mirrors which are divided into 400 segments to modulate light focusing through the scattering media using advanced genetic algorithm. Light intensity at the target position is enhanced up to 50+/-5 times the average speckle intensity. The diameters of focusing spot can be changed ranging from 7 μm to 70 μm at arbitrary positions and multiple foci are obtained simultaneously. The spatial arrangement of multiple foci can be flexibly controlled. The advantage of DMDs lies in their switching speed up to 30 kHz, which has the potential to generate a focus in an ultra-short period of time. Our work provides a reference for the study of high speed wavefront shaping that is required in vivo tissues imaging.

  9. Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation.

    PubMed

    Tripathi, Kaushlendra; Hussein, Usama K; Anupalli, Roja; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P; Owen, Laurie B; Piazza, Gary A; Palle, Komaraiah

    2015-03-10

    Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC.

  10. The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

    PubMed

    Mai, Kien T; Burns, Bruce F; Stinson, William A; Morash, Christopher

    2007-03-01

    Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.

  11. Sensorless adaptive optics for isoSTED nanoscopy

    NASA Astrophysics Data System (ADS)

    Antonello, Jacopo; Hao, Xiang; Allgeyer, Edward S.; Bewersdorf, Joerg; Rittscher, Jens; Booth, Martin J.

    2018-02-01

    The presence of aberrations is a major concern when using fluorescence microscopy to image deep inside tissue. Aberrations due to refractive index mismatch and heterogeneity of the specimen under investigation cause severe reduction in the amount of fluorescence emission that is collected by the microscope. Furthermore, aberrations adversely affect the resolution, leading to loss of fine detail in the acquired images. These phenomena are particularly troublesome for super-resolution microscopy techniques such as isotropic stimulated-emission-depletion microscopy (isoSTED), which relies on accurate control of the shape and co-alignment of multiple excitation and depletion foci to operate as expected and to achieve the super-resolution effect. Aberrations can be suppressed by implementing sensorless adaptive optics techniques, whereby aberration correction is achieved by maximising a certain image quality metric. In confocal microscopy for example, one can employ the total image brightness as an image quality metric. Aberration correction is subsequently achieved by iteratively changing the settings of a wavefront corrector device until the metric is maximised. This simplistic approach has limited applicability to isoSTED microscopy where, due to the complex interplay between the excitation and depletion foci, maximising the total image brightness can lead to introducing aberrations in the depletion foci. In this work we first consider the effects that different aberration modes have on isoSTED microscopes. We then propose an iterative, wavelet-based aberration correction algorithm and evaluate its benefits.

  12. Early Detection Rapid Response Program Targets New Noxious Weed Species in Washington State

    ERIC Educational Resources Information Center

    Andreas, Jennifer E.; Halpern, Alison D.; DesCamp, Wendy C.; Miller, Timothy W.

    2015-01-01

    Early detection, rapid response is a critical component of invasive plant management. It can be challenging, however, to detect new invaders before they become established if landowners cannot identify species of concern. In order to increase awareness, eye-catching postcards were developed in Washington State as part of a noxious weed educational…

  13. The Role of Physical Contact and Association in Early Contamination Sensitivity.

    ERIC Educational Resources Information Center

    Springer, Ken; Belk, Amy

    1994-01-01

    Children were asked whether someone would get sick from drinking juice placed near a bug. Some preschoolers and most seven- and eight-year olds recognized the need for physical contact with the bug to make the juice noxious, whereas some believed the mere presence of a contaminant made it noxious. Thus, associational contamination sometimes plays…

  14. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    PubMed Central

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure. PMID:27445126

  15. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    NASA Astrophysics Data System (ADS)

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-07-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1-3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure.

  16. Dentigenous infectious foci – a risk factor of infective endocarditis

    PubMed Central

    Wisniewska-Spychala, Beata; Sokalski, Jerzy; Grajek, Stefan; Jemielity, Marek; Trojnarska, Olga; Choroszy-Król, Irena; Sójka, Anna; Maksymiuk, Tomasz

    2012-01-01

    Summary Background Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. Material/Methods The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. Results Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. Conclusions Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID:22293883

  17. Quality of life in childhood epilepsy with lateralized epileptogenic foci.

    PubMed

    Mathiak, Krystyna A; Luba, Małgorzata; Mathiak, Klaus; Karzel, Katarzyna; Wolańczyk, Tomasz; Szczepanik, Elzbieta; Ostaszewski, Paweł

    2010-08-17

    Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

  18. Quality of life in childhood epilepsy with lateralized epileptogenic foci

    PubMed Central

    2010-01-01

    Background Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. Methods Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. Results We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. Conclusions We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development. PMID:20716372

  19. Fibre optic confocal imaging (FOCI) for subsurface microscopy of the colon in vivo.

    PubMed Central

    Delaney, P M; King, R G; Lambert, J R; Harris, M R

    1994-01-01

    Fibre optic confocal imaging (FOCI) is a new type of microscopy which has been recently developed (Delaney et al. 1993). In contrast to conventional light microscopy, FOCI and other confocal techniques allow clear imaging of subsurface structures within translucent objects. However, unlike conventional confocal microscopes which are bulky (because of a need for accurate alignment of large components) FOCI allows the imaging end to be miniaturised and relatively mobile. FOCI is thus particularly suited for clear subsurface imaging of structures within living animals or subjects. The aim of the present study was to assess the suitability of using FOCI for imaging of subsurface structures within the colon, both in vitro (human and rat biopsies) and in vivo (in rats). Images were obtained in fluorescence mode (excitation 488 nm, detection above 515 nm) following topical application of fluorescein. By this technique the glandular structure of the colon was imaged. FOCI is thus suitable for subsurface imaging of the colon in vivo. Images Fig. 2 Fig. 3 PMID:8157487

  20. FOCIS goes south: advances in translational and clinical immunology.

    PubMed

    Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

    2017-09-01

    FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

  1. Stochastic properties of radiation-induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci.

    PubMed

    Ponomarev, Artem L; Costes, Sylvain V; Cucinotta, Francis A

    2008-11-01

    We computed probabilities to have multiple double-strand breaks (DSB), which are produced in DNA on a regional scale, and not in close vicinity, in volumes matching the size of DNA damage foci, of a large chromatin loop, and in the physical volume of DNA containing the HPRT (human hypoxanthine phosphoribosyltransferase) locus. The model is based on a Monte Carlo description of DSB formation by heavy ions in the spatial context of the entire human genome contained within the cell nucleus, as well as at the gene sequence level. We showed that a finite physical volume corresponding to a visible DNA repair focus, believed to be associated with one DSB, can contain multiple DSB due to heavy ion track structure and the DNA supercoiled topography. A corrective distribution was introduced, which was a conditional probability to have excess DSB in a focus volume, given that there was already one present. The corrective distribution was calculated for 19.5 MeV/amu N ions, 3.77 MeV/amu alpha-particles, 1000 MeV/amu Fe ions, and X-rays. The corrected initial DSB yield from the experimental data on DNA repair foci was calculated. The DSB yield based on the corrective function converts the focus yield into the DSB yield, which is comparable with the DSB yield based on the earlier PFGE experiments. The distribution of DSB within the physical limits of the HPRT gene was analyzed by a similar method as well. This corrective procedure shows the applicability of the model and empowers the researcher with a tool to better analyze focus statistics. The model enables researchers to analyze the DSB yield based on focus statistics in real experimental situations that lack one-to-one focus-to-DSB correspondance.

  2. Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: Role of tumor necrosis factor alpha and apoptosis

    PubMed Central

    Woller, Sarah A.; Huie, J. Russell; Hartman, John J.; Hook, Michelle A.; Miranda, Rajesh C.; Huang, Yung-Jen; Ferguson, Adam R.; Grau, James W.

    2014-01-01

    We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered one day after SCI, on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days, post-treatment. In addition, because the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is implicated in numerous injury-induced processes including pain hypersensitivity, we assessed the temporal and spatial expression of TNFα, TNF receptors, and several downstream signaling targets after stimulation. Our results showed that unlike sham surgery or SCI only, nociceptive stimulation following SCI induced mechanical sensitivity by 24 hours. These behavioral changes were accompanied by increased expression of TNFα. Cellular assessments of downstream targets of TNFα revealed that nociceptive stimulation increased the expression of caspase 8 and the active subunit (12 kDa) of caspase 3 at a time point consistent with the onset of mechanical allodynia, indicative of active apoptosis. In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24 hours post-stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling. PMID:25180012

  3. Evidence supporting pre-radiation elimination of oral foci of infection in head and neck cancer patients to prevent oral sequelae. A systematic review.

    PubMed

    Schuurhuis, Jennifer M; Stokman, Monique A; Witjes, Max J H; Dijkstra, Pieter U; Vissink, Arjan; Spijkervet, Frederik K L

    2015-03-01

    Pre-radiation dental screening of head-neck cancer patients aims to identify and eliminate oral foci of infection to prevent post-radiation oral problems. The evidence for the efficacy of dental screening is unclear. In this systematic review, we analyzed available evidence on the efficacy of pre-radiation elimination of oral foci of infection in preventing oral sequelae. A search was conducted (MEDLINE/EMBASE) for papers published up to May 2014. Papers on head-neck cancer patients subjected to pre-radiation dental screening, (chemo)radiation and oral follow-up were included. Of the 1770 identified papers, 20 studies fulfilled the inclusion criteria of which 17 were retrospective. A great heterogeneity in patient groups, dental screening techniques, definitions of oral foci of infection and techniques for eliminating foci was found. Most papers lacked essential details on how dental screening was performed and a clear definition of an oral focus of infection. The evidence for efficacy of elimination of oral foci of infection to prevent post-radiotherapy oral sequelae was inconclusive. Consequently, the efficacy of pre-radiation elimination of oral foci of infection remains unclear. No conclusions can be drawn about a definition of an oral focus of infection and whether pre-radiation elimination of these foci should be mandatory. We therefore suggest prospective studies with well-defined criteria for oral foci of infection, a clear description of which foci were eliminated and how, a detailed description of pre-radiation dental screening, clearly described patient and tumor characteristics, and a detailed dental history and dental status. Subsequently, oral problems that occur post-radiation should be systematically recorded. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Double strand break induction and kinetics indicate preserved hypersensitivity in keratinocytes to subtherapeutic doses for 7weeks of radiotherapy.

    PubMed

    Qvarnström, Fredrik; Simonsson, Martin; Nyman, Jan; Hermansson, Ingegerd; Book, Majlis; Johansson, Karl-Axel; Turesson, Ingela

    2017-01-01

    Previously we reported that hyper-radiosensitivity (HRS) was evidenced by quantifying DNA double strand break (DSB) foci in epidermis biopsies collected after delivering radiotherapeutic one and five dose fractions. The aim of this study was to determine whether HRS was preserved throughout a 7-week radiotherapy treatment, and also to examine the rate of foci decline and foci persistence between dose fractions. 42 patients with prostate cancer received 7-week fractionated radiotherapy treatment (RT) with daily dose fractions of 0.05-1.10Gy to the skin. Before RT, and at several times throughout treatment, skin biopsies (n=452) were collected at 30min, and 2, 3, 24, and 72h after dose fractions. DSB-foci markers, γH2AX and 53BP1, were labelled in epidermal keratinocytes with immunofluorescence and immunohistochemical staining. Foci were counted both with digital image analysis and manually. HRS in keratinocytes was evidenced by the dose-response relationships of DSB foci, observed throughout the treatment course, independent of sampling time and quantification method. Foci observed at 24h after dose fractions indicated considerable DSB persistence. Accordingly, foci significantly accumulated after 5 consecutive dose fractions. For doses below 0.3Gy, persistent foci could be observed even at 72h after damage induction. A comparison of γH2AX and 53BP1 quantifications in double-stained biopsies showed similar HRS dose-response relationships. These results represented the first evidence of preserved HRS, assessed by γH2AX- and 53BP1-labelled DSB foci, throughout a 7-week treatment course with daily repeated subtherapeutic dose fractions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. The Tao of treating weeds: Reaching for restoration in the northern Rocky Mountains

    Treesearch

    Lisa-Natalie Anjozian

    2008-01-01

    Noxious weeds are a serious problem that is spreading across the West. Herbicides such as Picloram have proven to be powerful tools in reducing weed invaders, although use of this tool has often produced unintended consequences. Broadleaf herbicides kill forbs, such as the noxious knapweed, but also harm native forbs such as arrowleaf balsamroot. Removing weedy forbs...

  6. Charting environmental pollution. [by noise measurements

    NASA Technical Reports Server (NTRS)

    Halpert, E.; Bizo, F.; Karacsonyi, Z.

    1974-01-01

    It is found that areas affected by different noxious agents are within the limits traced for high noise level areas; consequently, it is suggested that high noise pressure levels should be used as the primary indication of environmental pollution. A complex methodology is reported for charting environmental pollution due to physical, chemical and biological noxious agents on the scale of an industrial district.

  7. Topical hindpaw application of L-menthol decreases responsiveness to heat with biphasic effects on cold sensitivity of rat lumbar dorsal horn neurons

    PubMed Central

    Klein, Amanda H.; Sawyer, Carolyn M.; Takechi, Kenichi; Davoodi, Auva; Ivanov, Margaret A.; Carstens, Mirela Iodi; Carstens, E

    2012-01-01

    Menthol is used in pharmaceutical applications because of its desired cooling and analgesic properties. The neural mechanism by which topical application of menthol decreases heat pain is not fully understood. We investigated the effects of topical menthol application on lumbar dorsal horn wide dynamic range and nociceptive-specific neuronal responses to noxious heat and cooling of glaborous hindpaw cutaneous receptive fields. Menthol increased thresholds for responses to noxious heat in a concentration-dependent manner. Menthol had a biphasic effect on cold-evoked responses, reducing the threshold (to warmer temperatures) at a low (1%) concentration and increasing threshold and reducing response magnitude at high (10, 40%) concentrations. Menthol had little effect on responses to innocuous or noxious mechanical stimuli, ruling out a local anesthetic action. Application of 40% menthol to the contralateral hindpaw tended to reduce responses to cooling and noxious heat, suggesting a weak heterosegmental inhibitory effect. These results indicate that menthol has an analgesic effect on heat sensitivity of nociceptive dorsal horn neurons, as well as biphasic effects on cold sensitivity, consistent with previous behavioral observations. PMID:22687951

  8. Multiple environmental factor analysis in habitats of the harvest mite Neotrombicula autumnalis (Acari: Trombiculidae) suggests extraordinarily high euryoecious biology.

    PubMed

    Schöler, Arne; Maier, Walter A; Kampen, Helge

    2006-01-01

    The harvest mite Neotrombicula autumnalis (Trombiculidae) has become a great nuisance in various vegetated areas in Germany over the last 15 years. According to reports of dermatologists, this species appears to have propagated and spread significantly. Moreover, cases of severe trombidiosis or trombidiosis-like skin reactions have been noticed at unusually early times of the year. Due to the lack of scientific studies, little is known about the ecology of N. autumnalis and its distribution, and preferred habitats cannot be predicted. A four-year study was conducted to identify trombiculid foci in different areas of Bonn in order (1) to determine the timing of larvae appearance in different years, (2) to identify the factors that lead to high larvae abundances at the mite foci ('multiple factor analysis'), and (3) to develop an ecological control strategy. By means of the 'tile catch method' (TCM) which turned out to be most appropriate to collect data on the distribution and abundances of trombiculid mites, larvae of N. autumnalis were caught from mid July until the end of October/beginning of November. The distribution of the mites was patchy, supporting the hypothesis that certain factors cause a concentration in foci. Most of the mite foci had a fixed location for at least three years. Efforts to isolate nymphs and adults in larger quantities to gain knowledge about their preferred soil areas and soil depths failed. Only some nymphs of N. autumnalis could be found living 10-40 cm deep in the soil. Due to the restriction that the nymphs and adults can only rarely be isolated in the ground, the analysis of environmental factors was executed based on abundances of questing larvae on the soil surface. The detailed analysis of soil-physical, soil-chemical and meso-faunistic factors could not finally explain the unequal distribution of the mites, although the porosity of the soil had a statistically significant slight influence on the abundance of larvae, and soil pH bordered significance, also suggesting a slight influence. Furthermore, soil temperatures during the winter seasons in three subsequent years appeared too high to affect the harvest mite. The field experiments suggest that N. autumnalis and particularly its larval stages are extremely euryoecious (meaning tolerating very different environmental conditions). Further studies are necessary: additional investigations on the influence of certain abiotic environmental factors on N. autumnalis, the search for factors underlying the rhythmicity of its life cycle ('zeitgeber'), and the reasons and mechanisms for heterogeneous distribution of soil fauna in general. Ecological control of the mite is, in principle, possible but only after identifying the foci and ascertaining their approximate dimensions with the TCM. This control strategy is the most promising one, albeit very laborious, emphasising the need of further research on the ecology of the harvest mite.

  9. Recurrent mycobacterial osteomyelitis. Report of a case due to Mycobacterium avium-intracellulare-scrofulaceum complex and BCG vaccination.

    PubMed

    Solheim, L F; Kjelsberg, F

    1982-01-01

    A 28-year-old man suffering from recurrent mycobacterial osteomyelitis during several years is reported. Eight years old he had a Mycobacterium scrofulaceum infection in his right calcaneus. A serious infection with multiple foci of osteomyelitis occurred after BCG vaccination at the age of 14 years and 11 years later multifocal lesions of osteomyelitis due to Mycobacterium avium-intracellulare-scrofulaceum complex appeared. The special clinical problems due to the relative or complete resistence of these organisms to antituberculous drugs are emphasized. The mainstays of treatment are surgical revision and drainage with prolonged and intensive multiple drug therapy.

  10. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    PubMed Central

    Schuurhuis, J M; Span, L F R; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. Methods: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. Results: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. Conclusions: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID:27002936

  11. Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition.

    PubMed

    Matsumoto, Hotaru; Saitoh, Hisato

    2016-07-29

    We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.

    PubMed

    Hu, Jiaxin; Rong, Ziye; Gong, Xin; Zhou, Zhengyang; Sharma, Vivek K; Xing, Chao; Watts, Jonathan K; Corey, David R; Mootha, V Vinod

    2018-03-15

    Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.

  13. Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat.

    PubMed

    Sherman, S E; Loomis, C W

    1996-08-01

    Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.

  14. Thalamic VPM nucleus in the behaving monkey. III. Effects of reversible inactivation by lidocaine on thermal and mechanical discrimination.

    PubMed

    Duncan, G H; Bushnell, M C; Oliveras, J L; Bastrash, N; Tremblay, N

    1993-11-01

    1. The present study evaluates the necessity of the ventroposterior medial thalamic nucleus (VPM) for discrimination of the intensity of noxious heating, innocuous cooling, and innocuous tactile (airpuff) stimulation of the maxillary skin. 2. Two rhesus monkeys were trained to detect small differences (< 1.0 degrees C) in the intensity of noxious heat (near 46 degrees C) and innocuous cold (near 30 degrees C) as well as differences in the force of an airpuff applied to the skin over the maxilla. As a control the monkeys also detected small differences in the intensity of a white light. Lidocaine hydrochloride (2%) was microinjected into regions of thalamus where single-unit recordings had identified neuronal responses to the noxious heating and/or cooling stimuli. The effectiveness of the anesthetic blockade was monitored by multiunit recordings using microelectrodes positioned 1-3 mm from the orifice of the injection cannula. The monkey's ability to detect near-threshold changes in stimulus intensity was compared before and after each injection. 3. During six experimental sessions, single injections of 1-4 microliters lidocaine near the dorsomedial border of VPM did not significantly alter the monkey's ability to detect small changes in the intensity of noxious heat, cool, airpuff, or visual stimuli despite neurophysiological evidence that spontaneous neuronal activity was blocked within parts of VPM. 4. During three experiments, dual simultaneous microinjections of lidocaine (delivered through 2 microcannulae separated by approximately 1 mm) resulted in profound deficits in noxious heat discrimination, with lesser deficits in cool and airpuff discrimination; visual discrimination was never altered. Monitoring of adjacent microelectrodes revealed that although activity ventral to the injection sites was blocked, activity in medial thalamic nuclei, implicated in nociceptive processing, was probably not altered by these injections. 5. These data suggest that VPM is important for the perception of noxious and innocuous thermal stimuli as well as for the perception of tactile stimuli. However, considering the ineffectiveness of small single microinjections of lidocaine, it appears that some critical proportion of VPM must be inactivated to disrupt thermal or tactile discrimination, possibly because of overlapping receptive field properties of neurons in different areas of the nucleus.

  15. Analysis of transient receptor potential ankyrin 1 (TRPA1) in frogs and lizards illuminates both nociceptive heat and chemical sensitivities and coexpression with TRP vanilloid 1 (TRPV1) in ancestral vertebrates.

    PubMed

    Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto

    2012-08-31

    Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1.

  16. Analysis of Transient Receptor Potential Ankyrin 1 (TRPA1) in Frogs and Lizards Illuminates Both Nociceptive Heat and Chemical Sensitivities and Coexpression with TRP Vanilloid 1 (TRPV1) in Ancestral Vertebrates*

    PubMed Central

    Saito, Shigeru; Nakatsuka, Kazumasa; Takahashi, Kenji; Fukuta, Naomi; Imagawa, Toshiaki; Ohta, Toshio; Tominaga, Makoto

    2012-01-01

    Transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (V1) perceive noxious temperatures and chemical stimuli and are involved in pain sensation in mammals. Thus, these two channels provide a model for understanding how different genes with similar biological roles may influence the function of one another during the course of evolution. However, the temperature sensitivity of TRPA1 in ancestral vertebrates and its evolutionary path are unknown as its temperature sensitivities vary among different vertebrate species. To elucidate the functional evolution of TRPA1, TRPA1s of the western clawed (WC) frogs and green anole lizards were characterized. WC frog TRPA1 was activated by heat and noxious chemicals that activate mammalian TRPA1. These stimuli also activated native sensory neurons and elicited nocifensive behaviors in WC frogs. Similar to mammals, TRPA1 was functionally co-expressed with TRPV1, another heat- and chemical-sensitive nociceptive receptor, in native sensory neurons of the WC frog. Green anole TRPA1 was also activated by heat and noxious chemical stimulation. These results suggest that TRPA1 was likely a noxious heat and chemical receptor and co-expressed with TRPV1 in the nociceptive sensory neurons of ancestral vertebrates. Conservation of TRPV1 heat sensitivity throughout vertebrate evolution could have changed functional constraints on TRPA1 and influenced the functional evolution of TRPA1 regarding temperature sensitivity, whereas conserving its noxious chemical sensitivity. In addition, our results also demonstrated that two mammalian TRPA1 inhibitors elicited different effect on the TRPA1s of WC frogs and green anoles, which can be utilized to clarify the structural bases for inhibition of TRPA1. PMID:22791718

  17. c-Fos and pERK, which is a better marker for neuronal activation and central sensitization after noxious stimulation and tissue injury?

    PubMed Central

    Gao, Yong-Jing; Ji, Ru-Rong

    2009-01-01

    c-Fos, the protein of the protooncogene c-fos, has been extensively used as a marker for the activation of nociceptive neurons in the spinal cord for more than twenty years since Hunt et al. first reported that peripheral noxious stimulation to a hind paw of rats leads to a marked induction of c-Fos in superficial and deep dorsal horn neurons in 1987. In 1999, Ji et al. reported that phosphorylated extracellular signal-regulated kinase (pERK) is specifically induced by noxious stimulation in superficial dorsal horn neurons. Accumulating evidence indicates that pERK induction or ERK activation in dorsal horn neurons is essential for the development of central sensitization, increased sensitivity of dorsal horn neurons that is responsible for the generation of persistent pain. Further, molecular mechanisms underlying ERK-mediated central sensitization have been revealed. In contrast, direct evidence for c-Fos-mediated central sensitization is not sufficient. After a noxious stimulus (e.g., capsaicin injection) or tissue injury, c-Fos begins to be induced after 30-60 minutes, whereas pERK can be induced within a minute, which can correlate well with the development of pain hypersensitivity. While c-Fos is often induced in the nuclei of neurons, pERK can be induced in different subcellular structures of neurons such as nuclei, cytoplasma, axons, and dendrites. pERK can even be induced in spinal cord microglia and astrocytes after nerve injury. In summary, both c-Fos and pERK can be used as markers for neuronal activation following noxious stimulation and tissue injury, but pERK is much more dynamic and appears to be a better marker for central sensitization. PMID:19898681

  18. An equine pain face

    PubMed Central

    Gleerup, Karina B; Forkman, Björn; Lindegaard, Casper; Andersen, Pia H

    2015-01-01

    Objective The objective of this study was to investigate the existence of an equine pain face and to describe this in detail. Study design Semi-randomized, controlled, crossover trial. Animals Six adult horses. Methods Pain was induced with two noxious stimuli, a tourniquet on the antebrachium and topical application of capsaicin. All horses participated in two control trials and received both noxious stimuli twice, once with and once without an observer present. During all sessions their pain state was scored. The horses were filmed and the close-up video recordings of the faces were analysed for alterations in behaviour and facial expressions. Still images from the trials were evaluated for the presence of each of the specific pain face features identified from the video analysis. Results Both noxious challenges were effective in producing a pain response resulting in significantly increased pain scores. Alterations in facial expressions were observed in all horses during all noxious stimulations. The number of pain face features present on the still images from the noxious challenges were significantly higher than for the control trial (p = 0.0001). Facial expressions representative for control and pain trials were condensed into explanatory illustrations. During pain sessions with an observer present, the horses increased their contact-seeking behavior. Conclusions and clinical relevance An equine pain face comprising ‘low’ and/or ‘asymmetrical’ ears, an angled appearance of the eyes, a withdrawn and/or tense stare, mediolaterally dilated nostrils and tension of the lips, chin and certain facial muscles can be recognized in horses during induced acute pain. This description of an equine pain face may be useful for improving tools for pain recognition in horses with mild to moderate pain. PMID:25082060

  19. Pain assessment by continuous EEG: association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest.

    PubMed

    Nir, Rony-Reuven; Sinai, Alon; Raz, Einat; Sprecher, Elliot; Yarnitsky, David

    2010-07-16

    Recordings of neurophysiological brain responses to noxious stimuli have been traditionally based on short stimuli, in the order of milliseconds, which induce distinct event-related potentials (ERPs). However, using such stimuli in the experimental setting is disadvantageous as they are too brief to faithfully simulate clinical pain. We aimed at utilizing continuous EEG to investigate the properties of peak alpha frequency (PAF) as an objective cortical measure associated with subjective perception of tonic pain. Five minute long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with peak frequencies of alpha power-curves derived from central, temporal and frontal electrodes. NPSs and PAFs remained stable throughout the recording conditions (RM-ANOVAs; Ps>0.51). In the noxious condition, PAFs obtained at the bilateral temporal scalp were correlated with NPSs (Ps<0.001). Moreover, resting-state PAFs recorded at the bilateral temporal scalp were correlated with NPSs reported during the noxious condition (Ps<0.01). These psychophysical-neurophysiological relations attest to the properties of PAF as a novel cortical objective measure of subjective perception of tonic pain. Moreover, resting-state PAFs might hold inherent pain modulation attributes, possibly enabling the prediction of individual responsiveness to prolonged pain. The relevance of PAF to the neural processing of tonic pain may indicate its potential to advance pain research as well as clinical pain characterization. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  20. Dysmenorrhoea is associated with central changes in otherwise healthy women.

    PubMed

    Vincent, Katy; Warnaby, Catherine; Stagg, Charlotte J; Moore, Jane; Kennedy, Stephen; Tracey, Irene

    2011-09-01

    Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Drosophila TRP channels and animal behavior

    PubMed Central

    Fowler, Melissa A.; Montell, Craig

    2012-01-01

    Multiple classes of cell surface receptors and ion channels participate in the detection of changes in environmental stimuli, and thereby influence animal behavior. Among the many classes of ion channels, Transient Receptor Potential (TRP) cation channels are notable in contributing to virtually every sensory modality, and in controlling a daunting array of behaviors. TRP channels appear to be conserved in all metazoan organisms including worms, insects and humans. Flies encode 13 TRPs, most of which are expressed and function in sensory neurons, and impact behaviors ranging from phototaxis to thermotaxis, gravitaxis, the avoidance of noxious tastants and smells and proprioception. Multiple diseases result from defects in TRPs, and flies provide an excellent animal model for dissecting the mechanisms underlying “TRPopathies.” Drosophila TRPs also function in the sensation of botanically derived insect repellents, and related TRPs in insect pests are potential targets for the development of improved repellents to combat insect-borne diseases. PMID:22877650

  2. Subnuclear foci quantification using high-throughput 3D image cytometry

    NASA Astrophysics Data System (ADS)

    Wadduwage, Dushan N.; Parrish, Marcus; Choi, Heejin; Engelward, Bevin P.; Matsudaira, Paul; So, Peter T. C.

    2015-07-01

    Ionising radiation causes various types of DNA damages including double strand breaks (DSBs). DSBs are often recognized by DNA repair protein ATM which forms gamma-H2AX foci at the site of the DSBs that can be visualized using immunohistochemistry. However most of such experiments are of low throughput in terms of imaging and image analysis techniques. Most of the studies still use manual counting or classification. Hence they are limited to counting a low number of foci per cell (5 foci per nucleus) as the quantification process is extremely labour intensive. Therefore we have developed a high throughput instrumentation and computational pipeline specialized for gamma-H2AX foci quantification. A population of cells with highly clustered foci inside nuclei were imaged, in 3D with submicron resolution, using an in-house developed high throughput image cytometer. Imaging speeds as high as 800 cells/second in 3D were achieved by using HiLo wide-field depth resolved imaging and a remote z-scanning technique. Then the number of foci per cell nucleus were quantified using a 3D extended maxima transform based algorithm. Our results suggests that while most of the other 2D imaging and manual quantification studies can count only up to about 5 foci per nucleus our method is capable of counting more than 100. Moreover we show that 3D analysis is significantly superior compared to the 2D techniques.

  3. Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci.

    PubMed

    Mathes, Rachel L; Burdette, Erin L; Moore, Phillip A; Myrna, Kathern E

    2012-03-01

    To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. © 2011 American College of Veterinary Ophthalmologists.

  4. A Cajal body-independent pathway for telomerase trafficking in mice

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

    Tomlinson, Rebecca L.; Li, Jian; Culp, Bradley R.

    2010-10-15

    The intranuclear trafficking of human telomerase involves a dynamic interplay between multiple nuclear sites, most notably Cajal bodies and telomeres. Cajal bodies are proposed to serve as sites of telomerase maturation, storage, and assembly, as well as to function in the cell cycle-regulated delivery of telomerase to telomeres in human cells. Here, we find that telomerase RNA does not localize to Cajal bodies in mouse cells, and instead resides in separate nuclear foci throughout much of the cell cycle. However, as in humans, mouse telomerase RNA (mTR) localizes to subsets of telomeres specifically during S phase. The localization of mTRmore » to telomeres in mouse cells does not require coilin-containing Cajal bodies, as mTR is found at telomeres at similar frequencies in cells from wild-type and coilin knockout mice. At the same time, we find that human TR localizes to Cajal bodies (as well as telomeres) in mouse cells, indicating that the distinct trafficking of mTR is attributable to an intrinsic property of the RNA (rather than a difference in the mouse cell environment such as the properties of mouse Cajal bodies). We also find that during S phase, mTR foci coalesce into short chains, with at least one of the conjoined mTR foci co-localizing with a telomere. These findings point to a novel, Cajal body-independent pathway for telomerase biogenesis and trafficking in mice.« less

  5. Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs

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

    Guilloteau, L.; Pepin, M.; Pardon, P.

    1990-10-01

    The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored (1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and (2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteriamore » into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.« less

  6. γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

    PubMed

    Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

    2016-07-01

    DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. The Brain Proteome of the Ubiquitin Ligase Peli1 Knock-Out Mouse during Experimental Autoimmune Encephalomyelitis.

    PubMed

    Lereim, Ragnhild Reehorst; Oveland, Eystein; Xiao, Yichuan; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Sun, Shao-Cong; Berven, Frode S

    2016-09-01

    The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak. Brain samples from the frontal hemisphere, peripheral from the extensive inflammatory foci, were analyzed using TMT-labeling of sample pools, and the discovered proteins were verified in individual mice using label-free proteomics. The greatest proteomic differences between Peli1 knock-out and wild-type mice were observed at the disease peak. In Peli1 knock-out a higher degree of antigen presentation, increased activity of adaptive and innate immune cells and alterations to proteins involved in iron metabolism were observed during experimental autoimmune encephalomyelitis. These results unravel global effects to the brain proteome when abrogating Peli1 expression, underlining the importance of Peli1 as a regulator of the immune response also peripheral to inflammatory foci during experimental autoimmune encephalomyelitis. The proteomics data is available in PRIDE with accession PXD003710.

  8. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    PubMed Central

    Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

    2008-01-01

    Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm. PMID:18926833

  9. Objective scoring of transformed foci in BALB/c 3T3 cell transformation assay by statistical image descriptors.

    PubMed

    Urani, C; Corvi, R; Callegaro, G; Stefanini, F M

    2013-09-01

    In vitro cell transformation assays (CTAs) have been shown to model important stages of in vivo carcinogenesis and have the potential to predict carcinogenicity in humans. Advantages of CTAs are their ability of revealing both genotoxic and non-genotoxic carcinogens while reducing both experimental costs and the number of animals used. The endpoint of the CTA is foci formation, and requires classification under light microscopy based on morphology. Thus current limitations for the wide adoption of the assay partially depend on a fair degree of subjectivity in foci scoring. An objective evaluation may be obtained after separating foci from background monolayer in the digital image, and quantifying values of statistical descriptors which are selected to capture eye-scored morphological features. The aim of this study was to develop statistical descriptors to be applied to transformed foci of BALB/c 3T3, which cover foci size, multilayering and invasive cell growth into the background monolayer. Proposed descriptors were applied to a database of 407 foci images to explore the numerical features, and to illustrate open problems and potential solutions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Mild Social Stress in Mice Produces Opioid-Mediated Analgesia in Visceral but Not Somatic Pain States.

    PubMed

    Pitcher, Mark H; Gonzalez-Cano, Rafael; Vincent, Kathleen; Lehmann, Michael; Cobos, Enrique J; Coderre, Terence J; Baeyens, José M; Cervero, Fernando

    2017-06-01

    Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific mouse (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared with mice tested alone, suggesting that the mere presence of a stranger is stressful. We then observed noxious visceral or somatic stimulation-induced nociceptive behavior in mice tested alone or in mildly stressful conditions (ie, beside an unfamiliar stranger). Compared with mice tested alone, the presence of a stranger produced a dramatic opioid-dependent reduction in pain behavior associated with visceral but not somatic pain. This social stress-induced reduction of visceral pain behavior relied on visual but not auditory/olfactory cues. These findings suggest that visceral pain states may provoke heightened responsiveness to mild stressors, an effect that could interfere with testing outcomes during simultaneous behavioral testing of multiple rodents. In mice, mild social stress due to the presence of an unfamiliar conspecific mouse reduces pain behavior associated with noxious visceral but not somatic stimulation, suggesting that stress responsiveness may be enhanced in visceral pain versus somatic pain states. Published by Elsevier Inc.

  11. C. elegans multi-dendritic sensory neurons: morphology and function

    PubMed Central

    Albeg, Adi; Smith, Cody; Chatzigeorgiou, Marios; Feitelson, Dror G.; Hall, David H.; Schafer, William R.; Miller, David M.; Treinin, Millet

    2010-01-01

    PVD and FLP sensory neurons envelope the body of the C. elegans adult with a highly branched network of thin sensory processes. Both PVD and FLP neurons are mechanosensors. PVD is known to mediate the response to high threshold mechanical stimuli. Thus PVD and FLP neurons are similar in both morphology and function to mammalian nociceptors. To better understand the function of these neurons we generated strains lacking them. Behavioral analysis shows that PVD and FLP regulate movement under normal growth conditions, as animals lacking these neurons demonstrate higher dwelling behavior. In addition, PVD—whose thin branches project across the body-wall muscles—may have a role in proprioception, as ablation of PVD leads to defective posture. Moreover, movement-dependent calcium transients are seen in PVD, a response that requires MEC-10, a subunit of the mechanosensory DEG/ENaC channel that is also required for maintaining wild-type posture. Hence, PVD senses both noxious and innocuous signals to regulate C. elegans behavior, and thus combines the functions of multiple mammalian somatosensory neurons. Finally, strong mechanical stimulation leads to inhibition of egg-laying, and this response also depends on PVD and FLP neurons. Based on all these results we suggest that noxious signals perceived by PVD and FLP promote an escape behavior consisting of increased speed, reduced pauses and reversals, and inhibition of egg-laying. PMID:20971193

  12. Neonatal capsaicin treatment in rats affects TRPV1-related noxious heat sensation and circadian body temperature rhythm.

    PubMed

    Jeong, Keun-Yeong; Seong, Jinsil

    2014-06-15

    The transient receptor potential vanilloid 1 (TRPV1) is a cation channel that serves as a polymodal detector of noxious stimuli such as capsaicin. Therefore, capsaicin treatment has been used to investigate the physiological function of TRPV1. Here, we report physiological changes induced by treating neonatal rats with capsaicin. Capsaicin (50mg/kg) (cap-treated) or vehicle (vehicle-treated) was systemically administered to newborn SD rat pups within 48 h after birth. TRPV1 expression, intake volume of capsaicin water, and noxious heat sensation were measured 6 weeks after capsaicin treatment. Circadian body temperature and locomotion were recorded by biotelemetry. Expression of Per1, Per2, Bmal1 and Hsf1 (clock genes) was also investigated. Neonatal capsaicin treatment not only decreased TRPV1 expression but also induced desensitization to noxious heat stimuli. Circadian body temperature of cap-treated rats increased significantly compared with that of vehicle-treated rats. Additionally, the amplitude of the circadian body temperature was reversed in cap-treated rats. Expression of the hypothalamic Hsf1 and liver Per2 clock genes followed a similar trend. Therefore, we suggest that these findings will be useful in studying various physiological mechanisms related to TRPV1. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Corticomotor excitability during a noxious stimulus before and after exercise in women with fibromyalgia.

    PubMed

    Hoeger Bement, Marie K; Weyer, Andy D; Yoon, Tejin; Hunter, Sandra K

    2014-02-01

    The purposes of this study were to assess corticomotor excitability in people with fibromyalgia during a noxious stimulus before and after fatiguing exercise and examine associations with pain perception. Fifteen women with fibromyalgia completed three sessions: one familiarization and two experimental. The experimental sessions were randomized and involved measurement of pain perception and motor evoked potentials before and after (1) quiet rest and (2) isometric contraction of the elbow flexor muscles. Motor evoked potential amplitude of brachioradialis muscle was measured following transcranial magnetic stimulation delivered before, during, and after a noxious mechanical stimulus. After quiet rest, there was no change in pain perception. After the submaximal contraction, there was considerable variability in the pain response. Based on the changes in the experimental pain, subjects were divided into three groups (increase, decrease, and no change in pain). There was an interaction between pain response and the pain-induced change in motor evoked potentials. Those individuals who had an increase in motor evoked potentials during the pain test had an increase in pain after exercise. Thus, women with fibromyalgia were classified based on their pain response to exercise, and this response was associated with the change in corticomotor excitability during the application of a noxious stimulus.

  14. Localized air foci in the lower thorax in the patients with pneumothorax: skip pneumothoraces.

    PubMed

    Higuchi, Takeshi; Takahashi, Naoya; Kiguchi, Takao; Shiotani, Motoi; Maeda, Haruo

    2013-08-01

    To investigate the characteristics and imaging features of localized air foci in the lower thorax in patients with pneumothorax using thin-section multidetector computed tomography. Of 10,547 consecutive CT examinations comprising the chest, the CT scans of 146 patients with ordinary pneumothoraces were identified and retrospectively evaluated. The study group included 110 male and 36 female patients (mean age, 50 years; range, 1-93 years). All examinations were performed at our institution between January 2009 and December 2009. Cause of pneumothorax was classified as traumatic or non-traumatic. Localized air foci in the lower thorax were defined as being localized air collections in the lower thorax that did not appear to be adjacent to the lung. If these criteria were met, the shape, size, location laterality, and number of foci were evaluated. Associations with trauma, sex, severity of the pneumothorax, and laterality were evaluated using the χ(2) test. All P values <0.05 were considered significant. Localized air foci in the lower thorax presented as slit-like or small ovoid air collections in the lowest part of the pleural space. These foci were observed in 79/146 (54.1%) patients. The traumatic pneumothoraces group showed a higher prevalence of these features than the non-traumatic group. Some foci that were situated in the anterior part mimicked the appearance of free intraperitoneal air. Patients with pneumothorax commonly had localized air foci in the lower thorax. Because such foci can mimic pneumoperitoneum, accurate recognition of them is required to avoid confusion with free intraperitoneal air, especially in traumatic cases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, γ-H2AX formation, and Mre11 relocalization

    PubMed Central

    Limoli, Charles L.; Giedzinski, Erich; Bonner, William M.; Cleaver, James E.

    2002-01-01

    UV-induced replication arrest in the xeroderma pigmentosum variant (XPV) but not in normal cells leads to an accumulation of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX (γ-H2AX) in large nuclear foci at sites of stalled replication forks. These complexes have been shown to signal the presence of DNA damage, in particular, double-strand breaks (DSBs). This finding suggests that UV damage leads to the formation of DSBs during the course of replication arrest. After UV irradiation, XPV cells showed a fluence-dependent increase in the yield of γ-H2AX foci that paralleled the production of Mre11 foci. The percentage of foci-positive cells increased rapidly (10–15%) up to fluences of 10 J⋅m−2 before saturating at higher fluences. Frequencies of γ-H2AX and Mre11 foci both reached maxima at 4 h after UV irradiation. This pattern contrasts sharply to the situation observed after x-irradiation, where peak levels of γ-H2AX foci were found to precede the formation of Mre11 foci by several hours. The nuclear distributions of γ-H2AX and Mre11 were found to colocalize spatially after UV- but not x-irradiation. UV-irradiated XPV cells showed a one-to-one correspondence between Mre11 and γ-H2AX foci-positive cells. These results show that XPV cells develop DNA DSBs during the course of UV-induced replication arrest. These UV-induced foci occur in cells that are unable to carry out efficient bypass replication of UV damage and may contribute to further genetic variation. PMID:11756691

  16. Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

    PubMed

    Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

    2010-09-01

    Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

  17. Heterogeneity of DNA methylation in multifocal prostate cancer.

    PubMed

    Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

    2015-01-01

    Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data.

  18. Blood parameters and electroencephalographic responses of goats to slaughter without stunning.

    PubMed

    Sabow, A B; Goh, Y M; Zulkifli, I; Sazili, A Q; Kaka, U; Kadi, M Z A Ab; Ebrahimi, M; Nakyinsige, K; Adeyemi, K D

    2016-11-01

    The study compared changes in blood biochemistry, hormonal and electroencephalographic indices associated with possible noxious stimuli following neck cut slaughter in conscious, non-anaesthetized versus minimally-anaesthetized goats. Ten male Boer crossbreed goats were assigned into two groups and subjected to either slaughter conscious without stunning (SWS) or slaughter following minimal anaesthesia (SMA). Hormonal responses and changes in electroencephalographic (EEG) parameters were not influenced by slaughter method. The SWS goats had higher glucose and lactate than did SMA goats. It can be concluded that the noxious stimulus from the neck cut is present in both conscious and minimally anaesthetized goats. The application of slaughter without stunning causes changes in the EEG activities that are consistent with the presence of post slaughter noxious sensory input associated with tissue damage and would be expected to be experienced as pain in goats. Copyright © 2016. Published by Elsevier Ltd.

  19. Firewalls Prevent Systemic Dissemination of Vectors Derived from Human Adenovirus Type 5 and Suppress Production of Transgene-Encoded Antigen in a Murine Model of Oral Vaccination

    PubMed Central

    Revaud, Julien; Unterfinger, Yves; Rol, Nicolas; Suleman, Muhammad; Shaw, Julia; Galea, Sandra; Gavard, Françoise; Lacour, Sandrine A.; Coulpier, Muriel; Versillé, Nicolas; Havenga, Menzo; Klonjkowski, Bernard; Zanella, Gina; Biacchesi, Stéphane; Cordonnier, Nathalie; Corthésy, Blaise; Ben Arous, Juliette; Richardson, Jennifer P.

    2018-01-01

    To define the bottlenecks that restrict antigen expression after oral administration of viral-vectored vaccines, we tracked vectors derived from the human adenovirus type 5 at whole body, tissue, and cellular scales throughout the digestive tract in a murine model of oral delivery. After intragastric administration of vectors encoding firefly luciferase or a model antigen, detectable levels of transgene-encoded protein or mRNA were confined to the intestine, and restricted to delimited anatomical zones. Expression of luciferase in the form of multiple small bioluminescent foci in the distal ileum, cecum, and proximal colon suggested multiple crossing points. Many foci were unassociated with visible Peyer's patches, implying that transduced cells lay in proximity to villous rather than follicle-associated epithelium, as supported by detection of transgene-encoded antigen in villous epithelial cells. Transgene-encoded mRNA but not protein was readily detected in Peyer's patches, suggesting that post-transcriptional regulation of viral gene expression might limit expression of transgene-encoded antigen in this tissue. To characterize the pathways by which the vector crossed the intestinal epithelium and encountered sentinel cells, a fluorescent-labeled vector was administered to mice by the intragastric route or inoculated into ligated intestinal loops comprising a Peyer's patch. The vector adhered selectively to microfold cells in the follicle-associated epithelium, and, after translocation to the subepithelial dome region, was captured by phagocytes that expressed CD11c and lysozyme. In conclusion, although a large number of crossing events took place throughout the intestine within and without Peyer's patches, multiple firewalls prevented systemic dissemination of vector and suppressed production of transgene-encoded protein in Peyer's patches. PMID:29423380

  20. CAN ULTRASOUND ABDOMEN HELP IN EARLY DIAGNOSIS OF DIABETES MELLITUS? AN OBSERVATIONAL STUDY.

    PubMed

    Anwar, Javed; Aamir, Muhammad Omer; Sanaullah; Imdad, Zeeshan ul Hasnain; Parveen, Ishrat; Yousaf, Nasreen

    2015-01-01

    Diabetes mellitus is a common disease. Similarly, ultrasound findings of fatty change and renal crystals are commonly seen on ultrasound. In the personal observation of the main author over the past so many years it was noticed that Diabetes Mellitus, Fatty liver and renal crystals all sit well together. This study tries to establish a relationship between diabetes mellitus renal echogenic foci and fatty liver. This study is first of its kind, as nobody has ever before investigated an association between the renal echogenic foci and fatty liver in relation to diabetes mellitus. This cross-sectional, observational study was conducted at Radiology Department Combined Military Hospital, Kohat From 2nd June 2013 to 30th May 2014. Three hundred patients were collected on the basis of having fatty liver and renal echogenic foci on ultrasound and three hundred more patients were collected who had no fatty liver or renal echogenic foci on ultrasound. Their labs were done for diabetes mellitus. The patients having renal echogenic foci together with fatty liver had 83% positive rate of being diabetics, while patients with no fatty liver and no echogenic foci on ultrasonography had only 0.6% Positive rate of being diabetics. Our results provided the first demonstration of an association between renal echogenic foci together with fatty liver with the diabetes mellitus. Thus ultrasound examination of abdomen can be helpful in its early diagnosis if we make a protocol of doing fasting and random blood sugars in all those patients who have positive renal echogenic foci and fatty liver on their ultrasound examination.

  1. Automated analysis of time-lapse fluorescence microscopy images: from live cell images to intracellular foci.

    PubMed

    Dzyubachyk, Oleh; Essers, Jeroen; van Cappellen, Wiggert A; Baldeyron, Céline; Inagaki, Akiko; Niessen, Wiro J; Meijering, Erik

    2010-10-01

    Complete, accurate and reproducible analysis of intracellular foci from fluorescence microscopy image sequences of live cells requires full automation of all processing steps involved: cell segmentation and tracking followed by foci segmentation and pattern analysis. Integrated systems for this purpose are lacking. Extending our previous work in cell segmentation and tracking, we developed a new system for performing fully automated analysis of fluorescent foci in single cells. The system was validated by applying it to two common tasks: intracellular foci counting (in DNA damage repair experiments) and cell-phase identification based on foci pattern analysis (in DNA replication experiments). Experimental results show that the system performs comparably to expert human observers. Thus, it may replace tedious manual analyses for the considered tasks, and enables high-content screening. The described system was implemented in MATLAB (The MathWorks, Inc., USA) and compiled to run within the MATLAB environment. The routines together with four sample datasets are available at http://celmia.bigr.nl/. The software is planned for public release, free of charge for non-commercial use, after publication of this article.

  2. Placing pain on the sensory map: classic papers by Ed Perl and colleagues.

    PubMed

    Mason, Peggy

    2007-03-01

    This essay looks at two papers published by Ed Perl and co-workers that identified specifically nociceptive neurons in the periphery and superficial dorsal horn. Bessou P and Perl ER. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J Neurophysiol 32: 1025-1043 1969. Christensen BN and Perl ER. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol 33: 293-307 1970.

  3. Blockade of Opioid Receptors in the Medullary Reticularis Nucleus Dorsalis, but not the Rostral Ventromedial Medulla, Prevents Analgesia Produced by Diffuse Noxious Inhibitory Control in Rats With Muscle Inflammation

    PubMed Central

    de Resende, Marcos A.; Silva, Luis Felipe S.; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A.

    2014-01-01

    Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45°C and 47°C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. PMID:21330219

  4. Commandant's international technical series. Volume 9. International regulations on the prevention of pollution from ships carrying hazardous chemicals in bulk. Final report

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

    Not Available

    1985-12-01

    MARPOL was developed to minimize accidental and operational pollution from ships carrying noxious liquid substances in bulk. Accidental pollution could result from a collision, a grounding, or an overflow of a cargo tank. Operational pollution results from the disposal of cargo tank washings. Major amendments were made to the original Annex II by the International Maritime Organization. The United States and other States party to MARPOL will implement Annex II, as amended, on April 7, 1987. Implementation will affect seagoing ships transporting noxious liquid substances to and from such ships. The attached documents contain internationally agreed requirements, interpretations, and guidelinesmore » necessary for the implementation of Annex II. The documents attached include: (1) MARPOL Annex II as amended by amendments adopted by the twenty-second session of the IMO Marine Environment Protection Committee; (2) Unified Interpretations of Annex II; (3) Standards for the Procedures and Arrangements for the Discharge of Noxious Liquid Substances; (4) Ammendments to the Bulk Chemical Code and the International Bulk Chemical Code to include marine pollution concerns; (5) Guidelines on the Provision of Adequate Reception Facilities in Ports, Part II (Noxious Liquid Substances). The contents of these documents are being placed in regulations. The purpose of this document is to give members of the interested public advance notification of impending regulations.« less

  5. Autonomic responses to tonic pain are more closely related to stimulus intensity than to pain intensity.

    PubMed

    Nickel, Moritz M; May, Elisabeth S; Tiemann, Laura; Postorino, Martina; Ta Dinh, Son; Ploner, Markus

    2017-11-01

    Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences.

  6. The spino-bulbar-cerebellar pathway: Activation of neurons projecting to the lateral reticular nucleus in the rat in response to noxious mechanical stimuli.

    PubMed

    Huma, Zilli; Ireland, Kirsty; Maxwell, David J

    2015-03-30

    It is now well established that the cerebellum receives input from nociceptors which may serve to adjust motor programmes in response to pain and injury. In this study, we investigated the possibility that spinoreticular neurons (SRT) which project to a pre-cerebellar nucleus, the lateral reticular nucleus (LRt), respond to noxious mechanical stimulation. Seven adult male rats received stereotaxic injections of the b subunit of cholera toxin in the LRt. Following a 5 day interval, animals were anesthetised with urethane and a noxious mechanical stimulus was applied to the right hind paw. Animals were fixed by perfusion 5min following application of the stimulus. Retrogradely labelled SRT neurons of the lumbar spinal cord were examined for immunoreactivity for phosphorylated ERK (pERK) and the neurokinin-1 (NK-1) receptor. Approximately 15% of SRT cells in deep laminae (IV-VII and X) expressed pERK ipsilateral to the site of the stimulus. Around 60% of SRT cells with the NK-1 receptor expressed pERK but 5% of pERK expressing cells were negatively labelled for NK-1. It is concluded that a significant proportion of SRT cells projecting to the LRt respond to noxious mechanical stimuli and that one of the functions of this pathway may be to provide the cerebellum with nociceptive information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

    PubMed

    Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

    2018-05-01

    Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

  8. Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX

    PubMed Central

    McDonald, Robert J.; Ekins, Jacob B.; Tin, Anthony S.; Costes, Sylvain; Hudson, Tamara M.; Schroeder, Dana J.; Kallmes, Kevin; Kaufmann, Scott H.; Young, Philip M.; Lu, Aiming; Kadirvel, Ramanathan; Kallmes, David F.

    2018-01-01

    Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure. PMID:29309426

  9. X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

    PubMed

    Schwab, Siegfried A; Brand, Michael; Schlude, Ina-Kristin; Wuest, Wolfgang; Meier-Meitinger, Martina; Distel, Luitpold; Schulz-Wendtland, Ruediger; Uder, Michael; Kuefner, Michael A

    2013-01-01

    To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM) and to estimate foci after FFDM and digital breast-tomosynthesis (DBT) using a biological phantom model. The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. Median in-vivo foci level/cell was 0.086 (range 0.067-0.116) before and 0.094 (0.076-0.126) after FFDM (p = 0.0004). In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140) at skin level and 0.035 (range 0.030-0.050) at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081) at skin level and 0.015 (range 0.006-0.020) at glandular level. In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

  10. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    PubMed

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

  11. Persistence of γ-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to γ-rays or iron ions.

    PubMed

    Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V; Helen Barcellos-Hoff, Mary; Parvin, Bahram; Rydberg, Bjorn

    2011-07-01

    To investigate γ-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionising radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced γ-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both γ-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after γ-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. The disappearance of radiation-induced γ-H2AX and 53BP1 foci in HMEC has different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent γ-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double-strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodelling.

  12. THE LIVER OF WOODCHUCKS CHRONICALLY INFECTED WITH THE WOODCHUCK HEPATITIS VIRUS CONTAINS FOCI OF VIRUS CORE ANTIGEN NEGATIVE HEPATOCYTES WITH BOTH ALTERED AND NORMAL MORPHOLOGY

    PubMed Central

    Xu, Chunxiao; Yamamoto, Toshiki; Zhou, Tianlun; Aldrich, Carol E.; Frank, Katy; Cullen, John M.; Jilbert, Allison R.; Mason, William S.

    2007-01-01

    The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with “basophilic”, “amphophilic” and “clear cell” phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci. PMID:17078989

  13. In-vehicle extremity injuries from improvised explosive devices: current and future foci

    PubMed Central

    Ramasamy, Arul; Masouros, Spyros D.; Newell, Nicolas; Hill, Adam M.; Proud, William G.; Brown, Katherine A.; Bull, Anthony M. J.; Clasper, Jon C.

    2011-01-01

    The conflicts in Iraq and Afghanistan have been epitomized by the insurgents' use of the improvised explosive device against vehicle-borne security forces. These weapons, capable of causing multiple severely injured casualties in a single incident, pose the most prevalent single threat to Coalition troops operating in the region. Improvements in personal protection and medical care have resulted in increasing numbers of casualties surviving with complex lower limb injuries, often leading to long-term disability. Thus, there exists an urgent requirement to investigate and mitigate against the mechanism of extremity injury caused by these devices. This will necessitate an ontological approach, linking molecular, cellular and tissue interaction to physiological dysfunction. This can only be achieved via a collaborative approach between clinicians, natural scientists and engineers, combining physical and numerical modelling tools with clinical data from the battlefield. In this article, we compile existing knowledge on the effects of explosions on skeletal injury, review and critique relevant experimental and computational research related to lower limb injury and damage and propose research foci required to drive the development of future mitigation technologies. PMID:21149353

  14. Chromatin insulator bodies are nuclear structures that form in response to osmotic stress and cell death

    PubMed Central

    Schoborg, Todd; Rickels, Ryan; Barrios, Josh

    2013-01-01

    Chromatin insulators assist in the formation of higher-order chromatin structures by mediating long-range contacts between distant genomic sites. It has been suggested that insulators accomplish this task by forming dense nuclear foci termed insulator bodies that result from the coalescence of multiple protein-bound insulators. However, these structures remain poorly understood, particularly the mechanisms triggering body formation and their role in nuclear function. In this paper, we show that insulator proteins undergo a dramatic and dynamic spatial reorganization into insulator bodies during osmostress and cell death in a high osmolarity glycerol–p38 mitogen-activated protein kinase–independent manner, leading to a large reduction in DNA-bound insulator proteins that rapidly repopulate chromatin as the bodies disassemble upon return to isotonicity. These bodies occupy distinct nuclear territories and contain a defined structural arrangement of insulator proteins. Our findings suggest insulator bodies are novel nuclear stress foci that can be used as a proxy to monitor the chromatin-bound state of insulator proteins and provide new insights into the effects of osmostress on nuclear and genome organization. PMID:23878275

  15. A crucial role of constitutive androstane receptor (CAR) in liver tumor development by imazalil in mice.

    PubMed

    Tamura, Kei; Inoue, Kaoru; Takahashi, Miwa; Matsuo, Saori; Kodama, Yukio; Yoshida, Midori

    2016-01-01

    To clarify the major pathway of liver tumor development induced by imazalil (IMA), an imidazole fungicide, male constitutive androstane receptor (CAR)-knockout (CARKO) and wild-type (WT) mice were treated with IMA at 500 ppm in the diet up to 27 weeks after initiation by diethylnitrosamine. After 27 weeks of treatment, neither altered foci nor adenomas were significantly increased in CARKO mice, whereas both eosinophilic altered foci and adenomas were increased in WT mice. After 4 or 13 weeks of IMA treatment, liver hypertrophy was observed at the tumor-inducible dose without differences among genotypes or durations. Analysis of hepatic drug metabolite enzymes, performed after administration of multiple doses during a 1-week period, indicated that pregnane X receptor might be involved in liver hypertrophy because IMA markedly elevated Cyp3a11 and Cyp2b10 expression levels in a dose-dependent manner in both genotypes. Our results demonstrated that the CAR pathway was the main mechanism of liver tumor development induced by IMA. The carcinogenic pathway was different from that of liver hypertrophy.

  16. The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues.

    PubMed

    van der Laan, L N; de Ridder, D T D; Viergever, M A; Smeets, P A M

    2011-03-01

    Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies, 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. The formation of inflammatory demyelinated lesions in cerebral white matter

    PubMed Central

    Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

    2016-01-01

    Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

  18. [A case of chronic multifocal myositis].

    PubMed

    Maruyama, T; Kondo, K; Tabata, K; Yanagisawa, N

    1992-11-01

    A 61-year-old civil engineer began to have slowly progressive muscle atrophy in the right shoulder and the left arm at 56 years of age. Muscle wasting became manifest in the left thigh at 59 years and in the right thigh at 60 years. He had mild difficulty in climbing and descending stairs. On examination, although he had notable muscle atrophy in the right trapezius and proximal muscles in the upper and lower extremities, his muscle strength was relatively well preserved. The muscle atrophy was asymmetrical; the right periscapular region and the left upper and lower extremities were more markedly atrophic. In addition, multiple foci of the striking muscle atrophy were noted in the upper trunk and the proximal limb muscles. Fasciculation was not present. Deep tendon reflexes were normal with no pathologic reflexes. Except for a moderately elevated serum creatine kinase level of 709 Ul/l (normal 40-170) and mildly elevated serum myoglobin level of 100 ng/ml (normal < 60), no laboratory tests showed abnormal values suggesting an inflammatory process. Motor and sensory nerve conduction velocities were within normal limits. Electromyography disclosed myopathic and neuropathic changes. Computed tomography (CT) of skeletal muscles showed asymmetrical muscle atrophy and patchy low-density foci. In biopsied left quadriceps and right gastrocnemius muscles which showed partially low density on CT, there was marked variation in muscle fiber size, with necrotic and regenerating fibers, an increased number of centrally placed nuclei, and interstitial fibrosis. There were numerous foci of mononuclear inflammatory cellular infiltration, especially around the blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. The formation of inflammatory demyelinated lesions in cerebral white matter.

    PubMed

    Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

    2014-10-01

    Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

  20. Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.

    PubMed

    Marics, Irène; Malapert, Pascale; Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

    2014-01-01

    The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.

  1. Cooperative interaction among the various regulatory sites within the NMDA receptor-channel complex in modulating the evoked responses to noxious thermal stimuli of spinal dorsal horn neurons in the cat.

    PubMed

    Song, X J; Zhao, Z Q

    1998-05-01

    Interactions among antagonists acting at different regulatory sites within the N-methyl-D-aspartate (NMDA) receptor-channel complex on the evoked responses to noxious thermal stimuli of wide dynamic range (WDR) neurons in spinal dorsal horn were studied on 21 adult anesthetized and spinalized cats. The responses of nociceptive spinal dorsal horn neurons to noxious heating (45-55 degrees C) of the glabrous skin of the unilateral hind paw were reduced markedly by iontophoretically applied antagonists. The specific recognition site antagonist, DL-2-amino-5-phosphonovaleratic acid (APV), the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (7CKA), the polyamine site antagonist ifenprodil (IFEN), and the phencyclidine (PCP) site antagonists ketamine (KET) and MK-801 (40-100 nA) significantly reduced (t-tests, P < 0.01) the noxious thermal stimulus-evoked responses in about 70% of the neurons by (mean +/- SE) 54.1 +/- 5.8% (n = 19), 80.8 +/- 4.7% (n = 16), 51.1 +/- 6.4% (n = 10), 77 +/- 4.9% (n = 16) and 81.2 +/- 8.1% (n = 5), respectively. APV and IFEN were less effective in blocking noxious thermal stimuli-evoked responses than 7CKA, KET and MK-801 (ANOVA, P < 0.05). The responses were completely inhibited in some neurons. After co-administration of the antagonists, APV + 7CKA, APV + IFEN, 7CKA + IFEN, APV + KET and APV + MK-801, all at the subthreshold ejection current, the responses were reduced markedly in 13 of 16, 7 of 10, 5 of 10, 3 of 6 and 3 of 5 neurons, respectively. The present study suggests that blockage of any component of the NMDA receptor-channel complex antagonizes the NMDA receptor-mediated response, and that there are the cooperative interactions among the various regulatory sites within the NMDA receptor-channel complex in the transmission or modulation of spinal nociceptive thermal information.

  2. Secondary hyperalgesia phenotypes exhibit differences in brain activation during noxious stimulation.

    PubMed

    Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke; Mårtensson, Johan; Larsson, Henrik B W; Dahl, Jørgen Berg

    2015-01-01

    Noxious stimulation of the skin with either chemical, electrical or heat stimuli leads to the development of primary hyperalgesia at the site of injury, and to secondary hyperalgesia in normal skin surrounding the injury. Secondary hyperalgesia is inducible in most individuals and is attributed to central neuronal sensitization. Some individuals develop large areas of secondary hyperalgesia (high-sensitization responders), while others develop small areas (low-sensitization responders). The magnitude of each area is reproducible within individuals, and can be regarded as a phenotypic characteristic. To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47 °C, 7 min, 9 cm(2)) on the non-dominant lower-leg. Areas of secondary hyperalgesia were assessed 100 min after the injury. We measured neuronal activation by recording blood-oxygen-level-dependent-signals (BOLD-signals) during mechanical noxious stimulation before burn injury and in both primary and secondary hyperalgesia areas after burn-injury. In addition, T1-weighted images were used to measure differences in gray-matter density in cortical and subcortical regions of the brain. We found significant differences in neuronal activity between high- and low-sensitization responders at baseline (before application of the burn-injury) (p < 0.05). After the burn-injury, we found significant differences between responders during noxious stimulation of both primary (p < 0.01) and secondary hyperalgesia (p ≤ 0.04) skin areas. A decreased volume of the right (p = 0.001) and left caudate nucleus (p = 0.01) was detected in high-sensitization responders in comparison to low-sensitization responders. These findings suggest that brain-structure and neuronal activation to noxious stimulation differs according to secondary hyperalgesia phenotype. This indicates differences in central sensitization according to phenotype, which may have predictive value on the susceptibility to development of high-intensity acute and persistent pain.

  3. Acute Heat-Evoked Temperature Sensation Is Impaired but Not Abolished in Mice Lacking TRPV1 and TRPV3 Channels

    PubMed Central

    Reynders, Ana; Gaillard, Stéphane; Moqrich, Aziz

    2014-01-01

    The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation. PMID:24925072

  4. Origins of recently emerged foci of the tick Dermacentor reticulatus in central Europe inferred from molecular markers.

    PubMed

    Kloch, Agnieszka; Mierzejewska, Ewa J; Karbowiak, Grzegorz; Slivinska, Kateryna; Alsarraf, Mohammed; Rodo, Anna; Kowalec, Maciej; Dwużnik, Dorota; Didyk, Yuliya M; Bajer, Anna

    2017-04-15

    The ornate dog tick Dermacentor reticulatus is vector of several blood parasites, including Babesia canis, a causative agent of babesiosis. The geographical range of D. reticulatus in Europe is discontinuous with a gap separating eastern and western macroregions. New foci observed in several locations in western and central Europe were considered an expansion of the western population, including foci in western Poland. In the present paper we used molecular markers to identify the origins of these foci, and we compared their genetic polymorphism to D. reticulatus collected in sites situated within the eastern population. The overall polymorphism in mt 16S rDNA was low, and all sites from the western population shared the same haplotype suggesting the expansion in this area. In the marker 5.8S rDNA-ITS2 we found no differences in polymorphism between sites from eastern Poland (eastern population), and newly emerged foci in western Poland considered a putative expansion zone of the western population. However, the sites from western Poland differed considerably from nearby German site. Our results show that foci in western Poland could not have originated from D. reticulatus from the western population, as previously thought. We found that the state border following river hinders considerably gene flow between adjacent sites what suggest that natural dispersal of D. reticulatus by wildlife is unlikely, and the emergence of new foci should rather be contributed to human-associated dispersal. We propose that livestock, and pets travelling with their owners are the most probable source of new foci, and they can easily transfer ticks within a country but not between countries. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Automatic detection of DNA double strand breaks after irradiation using an γH2AX assay.

    PubMed

    Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Vordermark, Dyrk; Dehghani, Faramarz

    2018-05-01

    Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of "high" and "average" image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV)>0.98). In cases of "low" image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV>0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality.

  6. Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.

    PubMed

    Ekinci, Özgür; Öğüt, Betül; Çelik, Bülent; Dursun, Ayşe

    2018-06-01

    The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001). We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

  7. Influence of the environment and phototoxicity of the live cell imaging system at IMP microbeam facility

    NASA Astrophysics Data System (ADS)

    Liu, Wenjing; Du, Guanghua; Guo, Jinlong; Wu, Ruqun; Wei, Junzhe; Chen, Hao; Li, Yaning; Zhao, Jing; Li, Xiaoyue

    2017-08-01

    To investigate the spatiotemporal dynamics of DNA damage and repair after the ion irradiation, an online live cell imaging system has been established based on the microbeam facility at Institute of Modern Physics (IMP). The system could provide a sterile and physiological environment by making use of heating plate and live cell imaging solution. The phototoxicity was investigated through the evaluation of DNA repair protein XRCC1 foci formed in HT1080-RFP cells during the imaging exposure. The intensity of the foci induced by phototoxicity was much lower compared with that of the foci induced by heavy ion hits. The results showed that although spontaneous foci were formed due to RFP exposure during live cell imaging, they had little impact on the analysis of the recruitment kinetics of XRCC1 in the foci induced by the ion irradiation.

  8. [Stings, bites and other adventures...].

    PubMed

    De Dobbeleer, G

    2000-09-01

    Most of us live in cities and nature seems beneficial. Unfortunately, invertebrates and vertebrates may be aggressive. We will try here a review of the diseases caused by arthropods and other noxious animals. Injuries caused by the following insects will be described: mosquitoes, flies, fleas, bees, wasps and ants, bugs, beetles, butterflies and caterpillars. In the class arachnida: spiders, scopions, ticks and mites. Among invertebrates: leeches, anemons, corals, sea urchins, sponges and mollusca. Noxious or venomous vertebrates will not be forgotten. Basic and practical attitudes are proposed.

  9. Single Unit Recordings of Cells Responsive to Visual, Somatic, Acoustic, and Noxious Stimuli in the Superior Colliculus of the Golden Hamster.

    DTIC Science & Technology

    1978-08-01

    Acoustic, and Noxious Stimuli Thesis in the Superior Colliculus of the Golden 6. PERFORMING OG. REPORT NUMBER Hamster -. _ // 7. AUTHOR( a ) S. CONTRACT...OR GRANT NUMBER(s) James P. Dixon I - "JV 9. PERF 7 MING ORGANIZATION NAME A D10. PROGRAM ELEMENT, PROJECT, TASK AFIT Student at: Virginia...studied in the superior colliculus of the golden hamster. A laminar organiza- tion was observed with cells in the superficial layers responding exclusively

  10. Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Beck, Amanda P; Gray, Stanton B; Chaffee, Beth K

    2016-01-01

    Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date. PMID:27298251

  11. Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta).

    PubMed

    Beck, Amanda P; Gray, Stanton B; Chaffee, Beth K

    2016-01-01

    Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date.

  12. A Tikhonov Regularization Scheme for Focus Rotations with Focused Ultrasound Phased Arrays

    PubMed Central

    Hughes, Alec; Hynynen, Kullervo

    2016-01-01

    Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually-driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations. PMID:27913323

  13. A Tikhonov Regularization Scheme for Focus Rotations With Focused Ultrasound-Phased Arrays.

    PubMed

    Hughes, Alec; Hynynen, Kullervo

    2016-12-01

    Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound-phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations.

  14. Efficient multi-site two-photon functional imaging of neuronal circuits.

    PubMed

    Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

    2016-12-01

    Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

  15. Efficient multi-site two-photon functional imaging of neuronal circuits

    PubMed Central

    Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R.

    2016-01-01

    Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms. PMID:28018745

  16. Brain processing of pain in patients with unresponsive wakefulness syndrome

    PubMed Central

    Markl, Alexandra; Yu, Tao; Vogel, Dominik; Müller, Friedemann; Kotchoubey, Boris; Lang, Simone

    2013-01-01

    By definition, patients with unresponsive wakefulness syndrome (UWS) do not experience pain, but it is still not completely understood how far their brain can process noxious stimuli. The few positron emission tomography studies that have examined pain processing did not yield a clear and consistent result. We performed an functional magnetic resonance imaging scan in 30 UWS patients of nontraumatic etiology and 15 age- and sex-matched healthy control participants (HC). In a block design, noxious electrical stimuli were presented at the patients' left index finger, alternating with a resting baseline condition. Sixteen of the UWS patients (53%) showed neural activation in at least one subsystem of the pain-processing network. More specifically, 15 UWS patients (50%) showed responses in the sensory-discriminative pain network, 30% in the affective pain network. The data indicate that some patients completely fulfilling the clinical UWS criteria have the neural substrates of noxious stimulation processing, which resemble that in control individuals. We therefore suppose that at least some of these patients can experience pain. PMID:23533065

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

    Porter, Mark C.; Ketchum, Sarah

    Noxious weeds threaten fish and wildlife habitat by contributing to increased sedimentation rates, diminishing riparian structure and function, and reducing forage quality and quantity. Wallowa Resources Wallowa Canyonlands Partnership (WCP) protects the unique ecological and economic values of the Hells Canyon grasslands along lower Joseph Creek, the lower Grande Ronde and Imnaha Rivers from invasion and degradation by noxious weeds using Integrated Weed Management techniques. Objectives of this grant were to inventory and map high priority weeds, coordinate treatment of those weeds, release and monitor bio-control agents, educate the public as to the dangers of noxious weeds and how tomore » deal with them, and restore lands to productive plant communities after treatment. With collaborative help from partners, WCP inventoried {approx} 215,000 upland acres and 52.2 miles of riparian habitat, released bio-controls at 23 sites, and educated the public through posters, weed profiles, newspaper articles, and radio advertisements. Additionally, WCP used other sources of funding to finance the treatment of 1,802 acres during the course of this grant.« less

  18. Can crayfish take the heat? Procambarus clarkii show nociceptive behaviour to high temperature stimuli, but not low temperature or chemical stimuli

    PubMed Central

    Puri, Sakshi; Faulkes, Zen

    2015-01-01

    Nociceptors are sensory neurons that are tuned to tissue damage. In many species, nociceptors are often stimulated by noxious extreme temperatures and by chemical agonists that do not damage tissue (e.g., capsaicin and isothiocyanate). We test whether crustaceans have nociceptors by examining nociceptive behaviours and neurophysiological responses to extreme temperatures and potentially nocigenic chemicals. Crayfish (Procambarus clarkii) respond quickly and strongly to high temperatures, and neurons in the antenna show increased responses to transient high temperature stimuli. Crayfish showed no difference in behavioural response to low temperature stimuli. Crayfish also showed no significant changes in behaviour when stimulated with capsaicin or isothiocyanate compared to controls, and neurons in the antenna did not change their firing rate following application of capsaicin or isothiocyanate. Noxious high temperatures appear to be a potentially ecologically relevant noxious stimulus for crayfish that can be detected by sensory neurons, which may be specialized nociceptors. PMID:25819841

  19. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.

    PubMed

    Zhao, Ruohe; Zhou, Hang; Huang, Lianyan; Xie, Zhongcong; Wang, Jing; Gan, Wen-Biao; Yang, Guang

    2018-01-01

    The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  20. [THE EPIZOOTIC AND EPIDEMIC ACTIVITY OF NATURAL TULAREMIA FOCI OF DIFFERENT LANDSCAPE EPIDEMIOLOGICAL TYPES IN 2009-2014].

    PubMed

    Meshcheryakova, I S; Mikhailova, T V; Demidova, T N; Kormilitsyna, M I

    2016-01-01

    to assess the present state of the natural tularemia foci of different landscape epidemiological types, by using individual focal areas as an example. Epizootological monitoring and epidemiological analysis were conducted in the areas of natural tularemia foci of tundra (Wrangel Island), meadow-field (Central Federal District of the Russian Federation), flood-swamp (Arkhangelsk Region, Khanty-Mansi Autonomous District), and steppe (Mongolii) types. Small mammals (organs, blood), tularemia patients' sera, and environniental objects were examined. Molecular genetic and immune serological diagnostic assays were used. The incidence of tularemia in the past decade was analyzed using the maps for the epidemiological examinations of tularemia cases and medical reports. The natural foci of tularemia were established to continue to actively operate. There were 2913 cases of tularemia in the Russian Federation in 2001 to 2014. The flood-swamp natural foci, in which there were summer transmissive tularemia outbreaks, the largest of high occurred in Khanti-Mansiysk in 2013 when a total of 1005 people fell ill, are a special epidemic hazard. Analysis of the tularemia outbreaks suggests that there is a need for continuous epizootological monitoring of the areas of natural tularemia foci for the timely prediction and prevention of epidemic complications. It is noted that there is an unfounded reduction in the scope of preventive measures, and immunoprevention in particular, and a weaker control of the antitularemia immune status in the population residing in the area of active natural foci of tularemia.

  1. Eugenol and carvacrol excite first- and second-order trigeminal neurons and enhance their heat-evoked responses

    PubMed Central

    Klein, Amanda H.; Joe, Christopher L.; Davoodi, Auva; Takechi, Kenichi; Carstens, Mirela Iodi; Carstens, E

    2014-01-01

    Eugenol and carvacrol from clove and oregano, respectively, are agonists of the warmth-sensitive transient receptor potential channel TRPV3 and the irritant-sensitive TRPA1. Eugenol and carvacrol induce oral irritation that rapidly desensitizes, accompanied by brief enhancement of innocuous warmth and heat pain in humans. We presently investigated if eugenol and carvacrol activate nociceptive primary afferent and higher-order trigeminal neurons and enhance their heat-evoked responses, using calcium imaging of cultured trigeminal ganglion (TG) and dorsal root ganglion (DRG) neurons, and in vivo single-unit recordings in trigeminal subnucleus caudalis (Vc) of rats. Eugenol and carvacrol activated 20-30% of TG and 7-20% of DRG cells, the majority of which additionally responded to menthol, mustard oil and/or capsaicin. TG cell responses to innocuous (39°) and noxious (42°C) heating were enhanced by eugenol and carvacrol. We identified dorsomedial Vc neurons responsive to noxious heating of the tongue in pentobarbital-anesthetized rats. Eugenol and carvacrol dose-dependently elicited desensitizing responses in 55% and 73% of heat-sensitive units, respectively. Responses to noxious heat were briefly enhanced by eugenol and carvacrol. Many eugenol- and carvacrol-responsive units also responded to menthol, cinnamaldehyde and capsaicin. These data support a peripheral site for eugenol and carvacrol to enhance warmth- and noxious heat-evoked responses of trigeminal neurons, and are consistent with the observation that these agonists briefly enhance warmth and heat pain on the human tongue. PMID:24759772

  2. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

    PubMed Central

    Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura

    2016-01-01

    Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

  3. From the Dance of the Foci to a Strophoid

    ERIC Educational Resources Information Center

    Jobbings, Andrew

    2011-01-01

    The intersection of a plane and a cone is a conic section and rotating the plane leads to a family of conics. What happens to the foci of these conics as the plane rotates? A classical result gives the locus of the foci as an oblique strophoid when the plane rotates about a tangent to the cone. The analogous curve when the plane intersects a…

  4. Postural stability is altered by the stimulation of pain but not warm receptors in humans.

    PubMed

    Blouin, Jean-Sébastien; Corbeil, Philippe; Teasdale, Normand

    2003-10-17

    It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C) were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively). For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. The stimulation of the warm receptors (40 degrees C) did not induce any postural deterioration. With pain (45 degrees C), subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure). A non-noxious stimulation (40 degrees C) of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C) of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated) could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly) or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy).

  5. Investigation of a staged plasma-focus apparatus. [pinch construction and current sheet dynamics investigation

    NASA Technical Reports Server (NTRS)

    Lee, J. H.; Mcfarland, D. R.; Harries, W. L.

    1978-01-01

    A new staged plasma-focus geometry combining two Mather-type plasma-focus guns was constructed, and the current-sheet dynamics were investigated. The production of simultaneous pairs of plasma foci was achieved. The intensities of X-ray and fusion-neutron emission were measured and found to agree with the scaling law for a plasma focus. Advantages of this new geometry include the possibility of using plasma-focus type pinches in multiple arrays at power levels beyond the validity regime of the current scaling law for a single gun.

  6. Characterization of Aes nuclear foci in colorectal cancer cells

    PubMed Central

    Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M. Mark

    2016-01-01

    Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. PMID:26229111

  7. DNA Double-strand Breaks Induced byFractionated Neutron Beam Irradiation for Boron Neutron Capture Therapy.

    PubMed

    Kinashi, Yuko; Yokomizo, Natsuya; Takahashi, Sentaro

    2017-04-01

    To use the 53BP1 foci assay to detect DNA double-strand breaks induced by fractionated neutron beam irradiation of normal cells. The Kyoto University Research Reactor heavy-water facility and gamma-ray irradiation system were used as experimental radiation sources. After fixation of Chinese Hamster Ovary cells with 3.6% formalin, immunofluorescence staining was performed. Number and size of foci were analyzed using ImageJ software. Fractionated neutron irradiation induced 25% fewer 53BP1 foci than single irradiation at the same dose. By contrast, gamma irradiation induced 30% fewer 53BP1 foci than single irradiation at the same dose. Fractionated neutron irradiation induced larger foci than gamma irradiation, raising the possibility that persistent unrepaired DNA damage was amplified due to the high linear energy transfer component in the neutron beam. Unrepaired cluster DNA damage was more prevalent after fractionated neutron irradiation than after gamma irradiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. A comprehensive statistical classifier of foci in the cell transformation assay for carcinogenicity testing.

    PubMed

    Callegaro, Giulia; Malkoc, Kasja; Corvi, Raffaella; Urani, Chiara; Stefanini, Federico M

    2017-12-01

    The identification of the carcinogenic risk of chemicals is currently mainly based on animal studies. The in vitro Cell Transformation Assays (CTAs) are a promising alternative to be considered in an integrated approach. CTAs measure the induction of foci of transformed cells. CTAs model key stages of the in vivo neoplastic process and are able to detect both genotoxic and some non-genotoxic compounds, being the only in vitro method able to deal with the latter. Despite their favorable features, CTAs can be further improved, especially reducing the possible subjectivity arising from the last phase of the protocol, namely visual scoring of foci using coded morphological features. By taking advantage of digital image analysis, the aim of our work is to translate morphological features into statistical descriptors of foci images, and to use them to mimic the classification performances of the visual scorer to discriminate between transformed and non-transformed foci. Here we present a classifier based on five descriptors trained on a dataset of 1364 foci, obtained with different compounds and concentrations. Our classifier showed accuracy, sensitivity and specificity equal to 0.77 and an area under the curve (AUC) of 0.84. The presented classifier outperforms a previously published model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Potential Reporting Bias in Neuroimaging Studies of Sex Differences.

    PubMed

    David, Sean P; Naudet, Florian; Laude, Jennifer; Radua, Joaquim; Fusar-Poli, Paolo; Chu, Isabella; Stefanick, Marcia L; Ioannidis, John P A

    2018-04-17

    Numerous functional magnetic resonance imaging (fMRI) studies have reported sex differences. To empirically evaluate for evidence of excessive significance bias in this literature, we searched for published fMRI studies of human brain to evaluate sex differences, regardless of the topic investigated, in Medline and Scopus over 10 years. We analyzed the prevalence of conclusions in favor of sex differences and the correlation between study sample sizes and number of significant foci identified. In the absence of bias, larger studies (better powered) should identify a larger number of significant foci. Across 179 papers, median sample size was n = 32 (interquartile range 23-47.5). A median of 5 foci related to sex differences were reported (interquartile range, 2-9.5). Few articles (n = 2) had titles focused on no differences or on similarities (n = 3) between sexes. Overall, 158 papers (88%) reached "positive" conclusions in their abstract and presented some foci related to sex differences. There was no statistically significant relationship between sample size and the number of foci (-0.048% increase for every 10 participants, p = 0.63). The extremely high prevalence of "positive" results and the lack of the expected relationship between sample size and the number of discovered foci reflect probable reporting bias and excess significance bias in this literature.

  10. Apparent diffusive motion of centrin foci in living cells: implications for diffusion-based motion in centriole duplication

    NASA Astrophysics Data System (ADS)

    Rafelski, Susanne M.; Keller, Lani C.; Alberts, Jonathan B.; Marshall, Wallace F.

    2011-04-01

    The degree to which diffusion contributes to positioning cellular structures is an open question. Here we investigate the question of whether diffusive motion of centrin granules would allow them to interact with the mother centriole. The role of centrin granules in centriole duplication remains unclear, but some proposed functions of these granules, for example, in providing pre-assembled centriole subunits, or by acting as unstable 'pre-centrioles' that need to be captured by the mother centriole (La Terra et al 2005 J. Cell Biol. 168 713-22), require the centrin foci to reach the mother. To test whether diffusive motion could permit such interactions in the necessary time scale, we measured the motion of centrin-containing foci in living human U2OS cells. We found that these centrin foci display apparently diffusive undirected motion. Using the apparent diffusion constant obtained from these measurements, we calculated the time scale required for diffusion to capture by the mother centrioles and found that it would greatly exceed the time available in the cell cycle. We conclude that mechanisms invoking centrin foci capture by the mother, whether as a pre-centriole or as a source of components to support later assembly, would require a form of directed motility of centrin foci that has not yet been observed.

  11. Nanoscopic exclusion between Rad51 and 53BP1 after ion irradiation in human HeLa cells

    NASA Astrophysics Data System (ADS)

    Reindl, Judith; Drexler, Guido A.; Girst, Stefanie; Greubel, Christoph; Siebenwirth, Christian; Drexler, Sophie E.; Dollinger, Günther; Friedl, Anna A.

    2015-12-01

    Many proteins involved in detection, signalling and repair of DNA double-strand breaks (DSB) accumulate in large number in the vicinity of DSB sites, forming so called foci. Emerging evidence suggests that these foci are sub-divided in structural or functional domains. We use stimulated emission depletion (STED) microscopy to investigate localization of mediator protein 53BP1 and recombination factor Rad51 after irradiation of cells with low linear energy transfer (LET) protons or high LET carbon ions. With a resolution better than 100 nm, STED microscopy and image analysis using a newly developed analyzing algorithm, the reduced product of the differences from the mean, allowed us to demonstrate that with both irradiation types Rad51 occupies spherical regions of about 200 nm diameter. These foci locate within larger 53BP1 accumulations in regions of local 53BP1 depletion, similar to what has been described for the localization of Brca1, CtIP and RPA. Furthermore, localization relative to 53BP1 and size of Rad51 foci was not different after irradiation with low and high LET radiation. As expected, 53BP1 foci induced by low LET irradiation mostly contained one Rad51 focal structure, while after high LET irradiation, most foci contained >1 Rad51 accumulation.

  12. Race, ethnicity, and noxious facilities: Environmental racism re- examined

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

    Nieves, A.L.; Nieves, L.A.

    1992-10-01

    The charge has been made that hazardous facilities tend to be located in proximity to minority populations. This study uses a facility density measure for three categories of noxious facilities to examine the relationship between facilities and minority population concentrations. County-level data are used in a correlation analysis for African Americans, Hispanics, and Asians in the four major regions of the US. Even controlling for income and housing value, and limiting the data set to urban areas, consistent patterns of moderate to strong association of facility densities with minority population percentages are found.

  13. Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

    PubMed Central

    Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

    2014-01-01

    Background The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. Methods A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). Results The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). Conclusion Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa. PMID:24591813

  14. Carcinogenicity of by-products of disinfection in mouse and rat liver

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

    Herren-Freund, S.L.; Pereira, M.A.

    1986-11-01

    By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of ..gamma..-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylene, and N-Cl piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform either hadmore » no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA-initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-days-old Swiss mice initiated with ethylnitrosourea (ENU). ENU at 5 and 20 ..mu..g/g caused a dose-dependent increase in liver tumors. In male mice, chloroform inhibited both spontaneous and ENU-induced liver tumors. When administered in the drinking water, chloroform inhibited, whereas phenobarbital promoted, hepatocarcinogenesis in mice.« less

  15. Multiple polyps and colorectal cancer.

    PubMed

    Alecu, M; Simion, L; Straja, Nd; Brătucu, E

    2014-01-01

    Malignant degeneration as a possible course of evolution of colorectal polyps renders their diagnosis and therapeutic management a prophylactic act in the prevention of colorectal cancer (CRC). The study was conducted over a period of 3 years (2008-2011), during which 1,368 colonoscopies were performed in our service. The aim of the study was to identify patients presenting multiple colorectal polyps and to determine their risk factors for developing CRC, as well as to establish the appropriate therapeutic conduct. Presence of multiple polyps was recorded in over 40% of the patients identified with colorectal polyps of any kind. Dysplastic modifications observed during the histopathology exam presented a high incidence in the case of patients with multiple polyps, ranging from low-grade dysplasia to incipient CRC. Dysplastic modifications and carcinomatous foci were identified mostly among patients with multiple polyps.Only benign lesions or in situ carcinomas benefited from endoscopic treatment, poorly differentiated carcinomas or those invading the submucosa being treated by conventional surgery. Patients diagnosed with colorectal polyps require a rigorous post-therapy follow-up protocol, able to identify any eventual polyposis recurrence. Celsius.

  16. Transcriptomic Profiling of High-Density Giardia Foci Encysting in the Murine Proximal Intestine.

    PubMed

    Pham, Jonathan K; Nosala, Christopher; Scott, Erica Y; Nguyen, Kristofer F; Hagen, Kari D; Starcevich, Hannah N; Dawson, Scott C

    2017-01-01

    Giardia is a highly prevalent, understudied protistan parasite causing significant diarrheal disease worldwide. Its life cycle consists of two stages: infectious cysts ingested from contaminated food or water sources, and motile trophozoites that colonize and attach to the gut epithelium, later encysting to form new cysts that are excreted into the environment. Current understanding of parasite physiology in the host is largely inferred from transcriptomic studies using Giardia grown axenically or in co-culture with mammalian cell lines. The dearth of information about the diversity of host-parasite interactions occurring within distinct regions of the gastrointestinal tract has been exacerbated by a lack of methods to directly and non-invasively interrogate disease progression and parasite physiology in live animal hosts. By visualizing Giardia infections in the mouse gastrointestinal tract using bioluminescent imaging (BLI) of tagged parasites, we recently showed that parasites colonize the gut in high-density foci. Encystation is initiated in these foci throughout the entire course of infection, yet how the physiology of parasites within high-density foci in the host gut differs from that of cells in laboratory culture is unclear. Here we use BLI to precisely select parasite samples from high-density foci in the proximal intestine to interrogate in vivo Giardia gene expression in the host. Relative to axenic culture, we noted significantly higher expression (>10-fold) of oxidative stress, membrane transporter, and metabolic and structural genes associated with encystation in the high-density foci. These differences in gene expression within parasite foci in the host may reflect physiological changes associated with high-density growth in localized regions of the gut. We also identified and verified six novel cyst-specific proteins, including new components of the cyst wall that were highly expressed in these foci. Our in vivo transcriptome data support an emerging view that parasites encyst early in localized regions in the gut, possibly as a consequence of nutrient limitation, and also impact local metabolism and physiology.

  17. Transcriptomic Profiling of High-Density Giardia Foci Encysting in the Murine Proximal Intestine

    PubMed Central

    Pham, Jonathan K.; Nosala, Christopher; Scott, Erica Y.; Nguyen, Kristofer F.; Hagen, Kari D.; Starcevich, Hannah N.; Dawson, Scott C.

    2017-01-01

    Giardia is a highly prevalent, understudied protistan parasite causing significant diarrheal disease worldwide. Its life cycle consists of two stages: infectious cysts ingested from contaminated food or water sources, and motile trophozoites that colonize and attach to the gut epithelium, later encysting to form new cysts that are excreted into the environment. Current understanding of parasite physiology in the host is largely inferred from transcriptomic studies using Giardia grown axenically or in co-culture with mammalian cell lines. The dearth of information about the diversity of host-parasite interactions occurring within distinct regions of the gastrointestinal tract has been exacerbated by a lack of methods to directly and non-invasively interrogate disease progression and parasite physiology in live animal hosts. By visualizing Giardia infections in the mouse gastrointestinal tract using bioluminescent imaging (BLI) of tagged parasites, we recently showed that parasites colonize the gut in high-density foci. Encystation is initiated in these foci throughout the entire course of infection, yet how the physiology of parasites within high-density foci in the host gut differs from that of cells in laboratory culture is unclear. Here we use BLI to precisely select parasite samples from high-density foci in the proximal intestine to interrogate in vivo Giardia gene expression in the host. Relative to axenic culture, we noted significantly higher expression (>10-fold) of oxidative stress, membrane transporter, and metabolic and structural genes associated with encystation in the high-density foci. These differences in gene expression within parasite foci in the host may reflect physiological changes associated with high-density growth in localized regions of the gut. We also identified and verified six novel cyst-specific proteins, including new components of the cyst wall that were highly expressed in these foci. Our in vivo transcriptome data support an emerging view that parasites encyst early in localized regions in the gut, possibly as a consequence of nutrient limitation, and also impact local metabolism and physiology. PMID:28620589

  18. Integrative Genomic Analysis of Coincident Cancer Foci Implicates CTNNB1 and PTEN Alterations in Ductal Prostate Cancer.

    PubMed

    Gillard, Marc; Lack, Justin; Pontier, Andrea; Gandla, Divya; Hatcher, David; Sowalsky, Adam G; Rodriguez-Nieves, Jose; Vander Griend, Donald; Paner, Gladell; VanderWeele, David

    2017-12-08

    Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown. To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient. Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses. Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified. Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes. Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes. The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways. Published by Elsevier B.V.

  19. [Comparative analysis of the semiotics of disseminated pulmonary tuberculosis and exogenous allergic alveolitis in accordance with the data of computed tomography].

    PubMed

    Amansakhedov, R B; Limarova, I V; Perfiliev, A V; Abdullaev, R Yu; Sigaev, A T; Ergeshov, A E

    2016-01-01

    to improve the differential diagnosis of disseminated pulmonary tuberculosis (DPT) and exogenous allergic alveolitis (EAA) via comparative investigation of their computed tomography (CT) semiotics and identification of the most informative diagnostic criteria. 70 patients, including 40 patients with DPT in a phase of infiltration and 30 patients with acute EAA, were studied using a Somatom Emotion 16 multi-slice spiral CT scanner (Siemens). All the patients underwent spiral scanning from the upper chest aperture to the costodiaphragmatic recesses with a high CT algorithm at 0.8-mm slice thickness and a 1.5-mm step. Analysis of the spread of dissemination foci established that pathological changes were peribronchovascularly located in both nosological entities and characterized by a preponderance of septal and intrabronchial locations in DPT and by a centrilobular distribution in EAA. Centrilobular foci were more commonly poorly defined in EAA and mixed foci were observed in DPT. In the latter, peribronchovascular, centrilobular foci were revealed at a distance from the visceral pleura (the boundary of the deep and superficial lymphatic network, respectively) in 38% and more than half of the cases (62%) with the involvement of the visceral and parietal pleura; in EAA, the centrilobular foci were more often combined with the involvement of the visceral pleura in more than 92% of cases. The tree-in-bud sign was significantly more common in DPT. The latter was mostly characterized by apicocaudal regression of dissemination. In EAA, the foci were more frequently located asymmetrically. Monomorphic foci with destruction, as well as their polymorphism were seen in DPT; those without destruction were predominantly observed in EAA. CT ground glass and mosaic perfusion syndromes were significantly more often in EAA. In DPT, the visceral and parietal pleuras were involved in the process in 62% of cases and changes were also more common in the extrapleural fat. In addition to the peribronchovascular location of foci, the characteristic CT signs for DPT are a preponderance of intrabronchial and septal locations of foci, their apicocaudal regression, the presence of the CT tree-in-bud sign, and thickened extrapleural fat. EAA showed a prevalence of asymmetrical foci with centrilobular location with the involvement of the visceral pleura into the process, with the presence of CT ground glass and mosaic perfusion syndromes, as well as the bronchial lumen visualized in the peripheral segments of the lung.

  20. 5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

    PubMed Central

    Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

    2013-01-01

    Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

  1. Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas.

    PubMed

    Abou-El-Ardat, Khalil; Seifert, Michael; Becker, Kerstin; Eisenreich, Sophie; Lehmann, Matthias; Hackmann, Karl; Rump, Andreas; Meijer, Gerrit; Carvalho, Beatriz; Temme, Achim; Schackert, Gabriele; Schröck, Evelin; Krex, Dietmar; Klink, Barbara

    2017-04-01

    The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate GBM development. We present the first comprehensive study of 12 GBM foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing. Multifocal GBMs genetically resemble primary GBMs. Comparing foci from the same patient proved their monoclonal origin. All tumors harbored alterations in the 3 GBM core pathways: RTK/PI3K, p53, and RB regulatory pathways with aberrations of EGFR and CDKN2A/B in all (100%) patients. This unexpected high frequency reflects a distinct genetic signature of multifocal GBMs and might account for their highly malignant and invasive phenotype. Surprisingly, the types of mutations in these genes/pathways were different in tumor foci from the same patients. For example, we found distinct mutations/aberrations in PTEN, TP53, EGFR, and CDKN2A/B, which therefore must have occurred independently and late during tumor development. We also identified chromothripsis as a late event and in tumors with wild-type TP53. Only 2 events were found to be early in all patients: single copy loss of PTEN and TERT promoter point mutations. Multifocal GBMs develop through parallel genetic evolution. The high frequency of alterations in 3 main pathways suggests that these are essential steps in GBM evolution; however, their late occurrence indicates that they are not founder events but rather subclonal drivers. This might account for the marked genetic heterogeneity seen in primary GBM and therefore has important implications for GBM therapy. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

  2. 5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

    PubMed

    Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

    2013-01-01

    Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

  3. THE EFFECTS OF A HIGH ANIMAL FAT DIET ON THE INDUCTION OF ABERRANT CRYPT FOCI IN THE COLONS OF MALE F344/N RATS EXPOSED TO TRIHALOMETHANES IN THE DRINKING WATER

    EPA Science Inventory

    The Effects of a High Animal Fat Diet on the Induction of Aberrant Crypt Foci in the Colons of Male F344/N Rats Exposed to Trihalomethanes in the Drinking Water

    Abstract

    Aberrant crypt foci (ACF), identified as the putative precursor lesion in the development of co...

  4. Identification of Chinese plague foci from long-term epidemiological data

    PubMed Central

    Ben-Ari, Tamara; Neerinckx, Simon; Agier, Lydiane; Cazelles, Bernard; Xu, Lei; Zhang, Zhibin; Fang, Xiye; Wang, Shuchun; Liu, Qiyong; Stenseth, Nils C.

    2012-01-01

    Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed. PMID:22570501

  5. A novel multivariate STeady-state index during general ANesthesia (STAN).

    PubMed

    Castro, Ana; de Almeida, Fernando Gomes; Amorim, Pedro; Nunes, Catarina S

    2017-08-01

    The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.

  6. Effects of noxious stimuli on the electroencephalogram of anaesthetised chickens (Gallus gallus domesticus).

    PubMed

    McIlhone, Amanda E; Beausoleil, Ngaio J; Kells, Nikki J; Mellor, David J; Johnson, Craig B

    2018-01-01

    The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing.

  7. Local subcutaneous injection of chlorogenic acid inhibits the nociceptive trigeminal spinal nucleus caudalis neurons in rats.

    PubMed

    Kakita, Kaede; Tsubouchi, Hirona; Adachi, Mayu; Takehana, Shiori; Shimazu, Yoshihito; Takeda, Mamoru

    2017-11-29

    Acute administration of chlorogenic acid (CGA) in vitro was recently shown to modulate potassium channel conductance and acid-sensing ion channels (ASICs) in the primary sensory neurons; however, in vivo peripheral effects of CGA on the nociceptive mechanical stimulation of trigeminal neuronal activity remains to be determined. The present study investigated whether local administration of CGA in vivo attenuates mechanical stimulation-induced excitability of trigeminal spinal nucleus caudalis neuronal (SpVc) activity in rats. Extracellular single-unit recordings were made of SpVc wide-dynamic range (WDR) neuronal activity elicited by non-noxious and noxious orofacial mechanical stimulation in pentobarbital anesthetized rats. The mean number of SpVc WDR neuronal firings responding to both non-noxious and noxious mechanical stimuli were significantly and dose-dependently inhibited by local subcutaneous administration of CGA (0.1-10mM), with the maximal inhibition of discharge frequency revealed within 10min and reversed after approximately 30min. The mean frequency of SpVc neuronal discharge inhibition by CGA was comparable to that by a local anesthetic, the sodium channel blocker, 1% lidocaine. These results suggest that local CGA injection into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via the activation of voltage-gated potassium channels and modulation of ASICs in the nociceptive nerve terminal of trigeminal ganglion neurons. Therefore, local injection of CGA could contribute to local anesthetic agents for the treatment of trigeminal nociceptive pain. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  8. Effects of noxious stimuli on the electroencephalogram of anaesthetised chickens (Gallus gallus domesticus)

    PubMed Central

    McIlhone, Amanda E.; Beausoleil, Ngaio J.; Mellor, David J.; Johnson, Craig B.

    2018-01-01

    The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species. The aim of the current study was to determine whether the MAM can be applied to the study of nociception in birds. Ten chickens were lightly anaesthetised with halothane and their EEG recorded using surface electrodes during the application of supramaximal mechanical, thermal and electrical noxious stimuli. Spectral analysis revealed no EEG responses to any of these stimuli. Given that birds possess the neural apparatus to detect and process pain, and that the applied noxious stimuli elicit behavioural signs of pain in conscious chickens, this lack of response probably relates to methodological limitations. Anatomical differences between the avian and mammalian brains, along with a paucity of knowledge regarding specific sites of pain processing in the avian brain, could mean that EEG recorded from the head surface is insensitive to changes in neural activity in the pain processing regions of the avian brain. Future investigations should examine alternative electrode placement sites, based on avian homologues of the mammalian brain regions involved in pain processing. PMID:29698446

  9. Effects of thermal stimulation, applied to the hindpaw via a hot water bath, upon ovarian blood flow in anesthetized nonpregnant rats.

    PubMed

    Uchida, Sae; Hotta, Harumi; Hanada, Tomoko; Okuno, Yuka; Aikawa, Yoshihiro

    2007-08-01

    The effects of thermal stimulation, applied to the hindpaw via a hot bath set to either 40 degrees C (non-noxious) or 49 degrees C (noxious), upon ovarian blood flow were examined in nonpregnant anesthetized rats. Ovarian blood flow was measured using a laser Doppler flowmeter. Blood pressure was markedly increased following 49 degrees C stimulation. Ovarian blood flow, however, showed no obvious change during stimulation, although a small increase was observed after stimulation. Ovarian blood flow and blood pressure responses to 49 degrees C stimulation were abolished after hindlimb somatic nerves proximal to the stimuli were cut. Heat stimulation (49 degrees C) resulted in remarkable increases in both ovarian blood flow and blood pressure in rats in which the sympathetic nerves supplying the ovary were cut but the hindlimb somatic nerves remained intact. The efferent activity of the ovarian plexus nerve was increased during stimulation at 49 degrees C. Stimulation at 40 degrees C had no effect upon ovarian blood flow, blood pressure or ovarian plexus nerve activity. Electrical stimulation of the distal part of the severed ovarian plexus nerve resulted in a decrease in both the diameter of ovarian arterioles, observed using a digital video microscope, and ovarian blood flow.The present results demonstrate that noxious heat, but not non-noxious warm, stimulation of the hindpaw skin in anesthetized rats influences ovarian blood flow in a manner that is attributed to reflex responses in ovarian sympathetic nerve activity and blood pressure.

  10. Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila

    PubMed Central

    Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.

    2016-01-01

    The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967

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

    Lupo, Janine M., E-mail: janine.lupo@ucsf.edu; Chuang, Cynthia F.; Chang, Susan M.

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation.more » These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.« less

  12. Melamine-induced urinary calculi in infants--sonographic manifestations and outcomes 1 year after exposure.

    PubMed

    Nie, Fang; Li, Xin-jie; Shang, Pan-feng; Wang, Ying

    2013-04-01

    In 2008, the melamine-tainted-milk incident started with reports of increased incidence of urolithiasis in infants in China. Affected children were screened for urolithiasis. The purpose of this study was to analyze sonographic characterization of infant melamine-induced urolithiasis. Transabdominal US examination was done in 603 infants with melamine-induced calculi. The imaging characteristics of calculi and hydronephrosis were analyzed. Follow-up US imaging was performed. Comet-tail sign was seen behind the calculus of <4 mm. Calculi of ≥ 4 mm were found in 299 inpatients with clear posterior border and with or without light shadowing. Solitary and multiple stones had similar incidence. Incidence of calculi in the inferior renal calyx was the highest (55.2%) in inpatients. Calculus size in inpatients age 2-3 years was smaller than that of children younger than 2 years old (P < 0.05). Inpatients age 2-3 years had the highest incidence rate (48.0%) of hydronephrosis. Calculi of <4 mm manifested as hyperechoic foci near the renal papillae, while calculi of ≥ 4 mm usually manifested as echogenic foci with visible inferior edge in the renal calyx. Hydronephrosis was a common imaging finding in inpatients ages 2-3 years.

  13. Salivary gland oncocytes in African hedgehogs (Atelerix albiventris) mimicking cytomegalic inclusion disease.

    PubMed

    Brunnert, S R; Hensley, G T; Citino, S B; Herron, A J; Altman, N H

    1991-07-01

    The salivary glands from three African hedgehogs contained multiple foci of cytomegalic cells, which occasionally had a mild to moderate infiltrate of lymphocytes at the periphery. The cytomegalic cells were 35 to 40 microns in diameter with abundant acidophilic granular to hyalin cytoplasm. The nuclei were enlarged with clumped marginalized chromatin and a large, (6 to 8 microns in diameter) central, brightly eosinophilic nucleolus that had the appearance of an inclusion body by light microscopy. Histochemically most of the cytomegalic cells contained cytoplasmic metachromatic granules with Feyrter's thionine inclusion stain. Scattered cells at the periphery of the cytomegalic foci contained periodic acid-Schiff-positive cytoplasmic granules. Ultrastructurally the cytomegalic cells contained numerous tightly-packed, often bizarre, enlarged mitochondria that completely filled the cytoplasm. The nucleus consisted of a dense central core of chromatin associated with the nucleolus and the remaining chromatin was clumped and marginalized. Nuclear and cytoplasmic virions consistent with cytomegalovirus were not present. Histochemical stains of the nucleus for heavy metals were negative. The ultrastructural and histochemical findings of the cytomegalic cells were consistent with oncocytes. Previous reports in the literature of similar cells in the salivary glands of insectivores appear to have been erroneously described as cytomegalovirus infections.

  14. Protein kinases are associated with multiple, distinct cytoplasmic granules in quiescent yeast cells.

    PubMed

    Shah, Khyati H; Nostramo, Regina; Zhang, Bo; Varia, Sapna N; Klett, Bethany M; Herman, Paul K

    2014-12-01

    The cytoplasm of the eukaryotic cell is subdivided into distinct functional domains by the presence of a variety of membrane-bound organelles. The remaining aqueous space may be further partitioned by the regulated assembly of discrete ribonucleoprotein (RNP) complexes that contain particular proteins and messenger RNAs. These RNP granules are conserved structures whose importance is highlighted by studies linking them to human disorders like amyotrophic lateral sclerosis. However, relatively little is known about the diversity, composition, and physiological roles of these cytoplasmic structures. To begin to address these issues, we examined the cytoplasmic granules formed by a key set of signaling molecules, the protein kinases of the budding yeast Saccharomyces cerevisiae. Interestingly, a significant fraction of these proteins, almost 20%, was recruited to cytoplasmic foci specifically as cells entered into the G0-like quiescent state, stationary phase. Colocalization studies demonstrated that these foci corresponded to eight different granules, including four that had not been reported previously. All of these granules were found to rapidly disassemble upon the resumption of growth, and the presence of each was correlated with cell viability in the quiescent cultures. Finally, this work also identified new constituents of known RNP granules, including the well-characterized processing body and stress granule. The composition of these latter structures is therefore more varied than previously thought and could be an indicator of additional biological activities being associated with these complexes. Altogether, these observations indicate that quiescent yeast cells contain multiple distinct cytoplasmic granules that may make important contributions to their long-term survival. Copyright © 2014 by the Genetics Society of America.

  15. Leptomeningeal contrast enhancement is associated with progression of cortical atrophy in MS: A retrospective, pilot, observational longitudinal study.

    PubMed

    Zivadinov, Robert; Ramasamy, Deepa P; Vaneckova, Manuela; Gandhi, Sirin; Chandra, Avinash; Hagemeier, Jesper; Bergsland, Niels; Polak, Paul; Benedict, Ralph Hb; Hojnacki, David; Weinstock-Guttman, Bianca

    2017-09-01

    Leptomeningeal contrast enhancement (LM CE) has been recently described in multiple sclerosis (MS) patients as a potential in vivo marker of cortical pathology. To investigate the association of LM CE and development of cortical atrophy in 50 MS patients (27 relapsing-remitting (RR) and 23 secondary-progressive (SP)) followed for 5 years. The presence and number of LM CE foci were assessed only at the 5-year follow-up using three-dimensional (3D) fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequence obtained 10 minutes after single dose of gadolinium injection on 3T scanner. The percentage change in whole brain, cortical and deep gray matter (GM) volumes, and lesion volume (LV) was measured between baseline and the 5-year follow-up. In total, 25 (50%) of MS patients had LM CE at the 5-year follow-up. Significantly more SPMS patients (12, 85.7%) had multiple LM CE foci, compared to those with RRMS (2, 18.2%) ( p = 0.001). MS patients with LM CE showed significantly greater percentage decrease in total GM (-3.6% vs -2%, d = 0.80, p = 0.006) and cortical (-3.4% vs -1.8%, d = 0.84, p = 0.007) volumes and greater percentage increase in ventricular cerebrospinal fluid (vCSF) volume (22.8% vs 9.9%, d = 0.90, p = 0.003) over the follow-up, compared to those without. In this retrospective, pilot, observational longitudinal study, the presence of LM CE was associated with progression of cortical atrophy over 5 years.

  16. γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

    PubMed Central

    Ding, Defang; Zhang, Yaping; Wang, Jing; Wang, Xufei; Fan, Dunhuang; He, Linfeng; Zhang, Xuxia; Gao, Yun; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

  17. Breast Cancer Risk by Extent and Type of Atypical Hyperplasia: An Update from the Nurses’ Health Studies

    PubMed Central

    Collins, Laura C.; Aroner, Sarah; Connolly, James L.; Colditz, Graham A.; Schnitt, Stuart J.; Tamimi, Rulla M.

    2015-01-01

    Background Women with atypical hyperplasia (AH) on a benign breast biopsy (BBB) are at increased risk for the development of breast cancer. However, the relationship between type and extent of AH (atypical ductal hyperplasia (ADH) vs. atypical lobular hyperplasia (ALH)) and magnitude of breast cancer risk is not well-defined. Methods We conducted a nested case-control study of benign breast disease and breast cancer risk. Women with breast cancer and a prior BBB (cases=488) were matched to women with a prior BBB but free from breast cancer (controls=1907). BBB slides were reviewed and categorized as either non-proliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Results Among women with ADH, the inter-relationship between extent of atypia and breast cancer risk was not significant (OR=3.5; 95%CI 2.2-5.6 for 1-2 foci, OR= 2.7; 95%CI 1.4-5.1 for ≥3 foci; p=0.58). Similarly, while the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR=5.2; 95%CI 2.7-10.0 for 1-2 foci; OR=8.0; 95%CI 4.5-14.2 for ≥3 foci; p=0.66). Conclusion This analysis demonstrates that the extent of ADH or ALH did not significantly contribute to breast cancer risk. The lack of a significant dose-response relationship between extent and type of atypia and breast cancer risk suggests that it would be premature to use extent of atypia to influence management decisions in women with ADH or ALH. PMID:26565738

  18. Extent of Atypical Hyperplasia Stratifies Breast Cancer Risk in Two Independent Cohorts of Women

    PubMed Central

    Degnim, Amy C.; Dupont, William D.; Radisky, Derek C.; Vierkant, Robert A.; Frank, Ryan D.; Frost, Marlene H.; Winham, Stacey J.; Sanders, Melinda E.; Smith, Jeffrey R.; Page, David L.; Hoskin, Tanya L.; Vachon, Celine M.; Ghosh, Karthik; Hieken, Tina J.; Denison, Lori A.; Carter, Jodi M.; Hartmann, Lynn C.; Visscher, Daniel W.

    2016-01-01

    Background Women with atypical hyperplasia (AH) on breast biopsy have a substantially increased risk of breast cancer (BC). Here we report BC risk with AH extent and subtype in two separate cohorts. Methods All samples containing AH were included from two cohorts of benign breast disease, Mayo Clinic and Nashville. Histology review quantified the number of foci of atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH). BC risk was stratified for number of AH foci within AH subtypes. Results The study included 708 Mayo and 466 Nashville AH subjects. In the Mayo Cohort, increasing foci of AH was associated with a significant increase in risk of BC, both for ADH (RR’s of 2.61, 5.21, and 6.36 for 1, 2, and 3+ foci, p=0.006 for linear trend) and for ALH (RR’s of 2.56, 3.50, and 6.79 for 1, 2, and 3+ foci, p=0.001 for linear trend). In the Nashville Cohort, RR’s of BC for ADH were 2.70, 5.17, and 15.06 for 1, 2, and 3+ foci respectively (p<0.001 for linear trend); for ALH, RR’s also increased but not significantly (2.61, 3.48, and 4.02, p=0.148). Combining both Mayo and Nashville samples, risk increased significantly for 1, 2, and 3+ foci: RR’s of 2.65, 5.19, and 8.94 for ADH (p<0.001), and 2.58, 3.49, and 4.97 for ALH (p=0.001). Conclusions In two independent cohort studies of benign breast disease, extent of atypia stratifies long-term breast cancer risk for ADH and ALH. PMID:27352219

  19. Relationship between increasing concentrations of two carcinogens and statistical image descriptors of foci morphology in the cell transformation assay.

    PubMed

    Callegaro, Giulia; Corvi, Raffaella; Salovaara, Susan; Urani, Chiara; Stefanini, Federico M

    2017-06-01

    Cell Transformation Assays (CTAs) have long been proposed for the identification of chemical carcinogenicity potential. The endpoint of these in vitro assays is represented by the phenotypic alterations in cultured cells, which are characterized by the change from the non-transformed to the transformed phenotype. Despite the wide fields of application and the numerous advantages of CTAs, their use in regulatory toxicology has been limited in part due to concerns about the subjective nature of visual scoring, i.e. the step in which transformed colonies or foci are evaluated through morphological features. An objective evaluation of morphological features has been previously obtained through automated digital processing of foci images to extract the value of three statistical image descriptors. In this study a further potential of the CTA using BALB/c 3T3 cells is addressed by analysing the effect of increasing concentrations of two known carcinogens, benzo[a]pyrene and NiCl 2 , with different modes of action on foci morphology. The main result of our quantitative evaluation shows that the concentration of the considered carcinogens has an effect on foci morphology that is statistically significant for the mean of two among the three selected descriptors. Statistical significance also corresponds to visual relevance. The statistical analysis of variations in foci morphology due to concentration allowed to quantify morphological changes that can be visually appreciated but not precisely determined. Therefore, it has the potential of providing new quantitative parameters in CTAs, and of exploiting all the information encoded in foci. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Novel Image Processing Interface to Relate DSB Spatial Distribution from Immunofluorescence Foci Experiments to the State-of-the-Art Models of DNA Breakage

    NASA Technical Reports Server (NTRS)

    Ponomarev, A. L.; Cucinotta, F. A.

    2004-01-01

    A recently developed software (NASARadiationTrackImage) allows a quick and automatic segmentation of foci that indicate spatial localization of specific proteins that are visualized by immunofluorescence. Of interest are the spatial and temporal distribution of foci such as gammaH2AX, a signal of the phosphorylation of a variant of the histone H2A that has been shown to correspond to DSBs, or proteins involved in DSB processing, such as ATM, Rad51, and p53, following exposures of human cells to high charge and energy (HZE) ion irradiation. Experimental data are recorded as sets of two-dimensional images in color with cells and foci of gammaH2AX, ATM, Rad51 or others shown. Different cells, levels of radiation and timing after radiation were recorded. The software allows us to calculate the number of foci per cell, overall intensity of light in foci and their spatial organization. A simple statistical model allows for testing of foci overlap (eclipse). A more complex statistical model previously known as DNAbreak simulates track structure and random chromosome geometry. It has one adjustable parameter corresponding to an average intensity of DSB creation in cubic micrometers of DNA volume per particle track or unit dose. Its limitation is the low-resolution limit both in physical space and DSB's along DNA. It works adequately on the scale of a cell and provides further insights on how the geometry of tracks and DNA affects genomic damage of the cell and subsequent repair. Future developments of the model for the description of the time evolution of DNA damage response proteins, and more robust track structure models will be discussed.

  1. Reliability of a Fully Automated Interpretation of γ -H2AX Foci in Lymphocytes of Moderately Trained Subjects under Resting Conditions.

    PubMed

    Heydenreich, Juliane; Otto, Christoph; Mayer, Frank; Carlsohn, Anja

    2014-01-01

    Background. Analysis of γ-H2AX foci is a promising approach to evaluate exercise-induced DNA damage. However, baseline levels and day-to-day variability of γ-H2AX foci have not been investigated in healthy subjects at rest. Methods. Blood was taken from eight moderately trained healthy males (29 ± 3 yrs, 1.84 ± 0.03 m, and 85 ± 6 kg) at two separate days (M1/M2) after 24-hour exercise cessation. Number of γ-H2AX foci per 100 lymphocytes (N), number of foci per affected lymphocyte (NAL), percentage of affected lymphocytes (PAL), and diameter (D) of γ-H2AX foci were analyzed (mean ± SD). Differences between M1 and M2 were analyzed using paired t-tests (α = 0.05). Day-to-day variability was evaluated by calculating the coefficients of variation (CV%), bias, and limits of agreement (LoA). Results. There were no statistically significant differences between M1 (N: 7.6 ± 4.4, NAL: 1.2 ± 0.2, PAL: 5.9 ± 2.6%, and D: 0.63 ± 0.07) and M2 (N: 8.4 ± 4.6, NAL: 1.3 ± 0.1, PAL: 6.9 ± 4.2%, and D: 0.66 ± 0.06). CV was calculated to be 98.5% (N), 88.9% (PAL), 11.3% (NAL), and 8.0% (D). Bias (LoA) was 0.75 (-15.2/13.7), -0.02 (-0.36/0.33), -1.0 (-11.9/9.9), and -0.04 (-0.16/0.09), respectively. Conclusions. Background level in healthy subjects is approximately 0.07 to 0.09 γ-H2AX foci/cell. NAL and D are reliable measures.

  2. Induction and quantification of gammma-H2AX foci following cx- and gamma-irradiaton

    NASA Technical Reports Server (NTRS)

    Leatherbarrow, E. L.; Cucinotta, F. A.; O'Neill, Peter

    2004-01-01

    Following DNA damage the histone H2AX becomes phosphorylated and can be visualised by immunofluorescence as an indicator of DSBs in individual cells. Using a wild type hamster cell line (V79-4) exposed to either a-particles or to Co-60 gamma-rays to induce DNA DSBs at different doses (20-200OmGy), the dose dependent induction of gamma-H2AX foci were scored both manually (by eye) and using image analysis. A linearly dependence on dose was found for both radiations. The number of DSBs determined by image analysis after a post-irradiation period of 30 minutes at 37 C, is 16.6 foci/cell/Gy for alpha-irradiation and 12.2 foci/cell/Gy for gamma-irradiation; the latter being 3-4 times the levels observed by eye and comparable to gamma-radiation-induced levels of prompt DSBs more recently reported using pulse field gel electrophoresis (approx. 16 DSBs/Gy). The average size of the gamma-H2AX foci induced by alpha-irradiation (0.30 square micrometers) is approximately 1.5 times larger than those induced by gamma-irradiation (0.19 square micrometers). The timescale of induction and removal of DSBs up to 24 hours post-irradiation, was investigated with gamma-H2AX foci levels found to remain significantly higher than controls for 4 or 6 hours in gamma-irradiated samples or alpha irradiated samples, respectively. These results demonstrate that not only gamma radiation but also alpha-radiation induce phosphorylation of the H2AX histone in response to DSBs even at low doses (20mGy for gamma-rays, 1 track/cell on average for alpha-particles) and the variation in size and dephosphorylation of the induced foci is dependent on radiation quality (LET).

  3. γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material.

    PubMed

    Menegakis, Apostolos; von Neubeck, Cläre; Yaromina, Ala; Thames, Howard; Hering, Sandra; Hennenlotter, Joerg; Scharpf, Marcus; Noell, Susan; Krause, Mechthild; Zips, Daniel; Baumann, Michael

    2015-09-01

    To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after >12h following ex vivo irradiation. Fitting the dose-response of residual γH2AX foci yielded slopes comparable with in situ irradiation of FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient-derived tumour samples were found. A novel clinically applicable method to quantify residual γH2AX foci in ex vivo irradiated tumour samples was established. The first clinical results suggest that this method allows to distinguish between radiosensitive and radioresistant tumour types. These findings support further translational evaluation of this assay to individualise radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Zoning, equity, and public health.

    PubMed

    Maantay, J

    2001-07-01

    Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems.

  5. Zoning, equity, and public health.

    PubMed Central

    Maantay, J

    2001-01-01

    Zoning, the most prevalent land use planning tool in the United States, has substantial implications for equity and public health. Zoning determines where various categories of land use may go, thereby influencing the location of resulting environmental and health impacts. Industrially zoned areas permit noxious land uses and typically carry higher environmental burdens than other areas. Using New York City as a case study, the author shows that industrial zones have large residential populations within them or nearby. Noxious uses tend to be concentrated in poor and minority industrial neighborhoods because more affluent industrial areas and those with lower minority populations are rezoned for other uses, and industrial zones in poorer neighborhoods are expanded. Zoning policies, therefore, can have adverse impacts on public health and equity. The location of noxious uses and the pollution they generate have ramifications for global public health and equity; these uses have been concentrated in the world's poorer places as well as in poorer places within more affluent countries. Planners, policymakers, and public health professionals must collaborate on a worldwide basis to address these equity, health, and land use planning problems. PMID:11441726

  6. Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

    PubMed

    Persinger, Michael A

    2009-01-01

    To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

  7. Characterization of Aes nuclear foci in colorectal cancer cells.

    PubMed

    Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M Mark

    2016-01-01

    Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  8. Spatial distribution of earthquake hypocenters in the Crimea—Black Sea region

    NASA Astrophysics Data System (ADS)

    Burmin, V. Yu; Shumlianska, L. O.

    2018-03-01

    Some aspects of the seismicity the Crime—Black Sea region are considered on the basis of the catalogued data on earthquakes that have occurred between 1970 and 2012. The complete list of the Crimean earthquakes for this period contains about 2140 events with magnitude ranging from -1.5 to 5.5. Bulletins contain information about compressional and shear waves arrival times regarding nearly 2000 earthquakes. A new approach to the definition of the coordinates of all of the events was applied to re-establish the hypocenters of the catalogued earthquakes. The obtained results indicate that the bulk of the earthquakes' foci in the region are located in the crust. However, some 2.5% of the foci are located at the depths ranging from 50 to 250 km. The new distribution of foci of earthquakes shows the concentration of foci in the form of two inclined branches, the center of which is located under the Yalto-Alushta seismic focal zone. The whole distribution of foci in depth corresponds to the relief of the lithosphere.

  9. Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

    PubMed Central

    Moseley, Graham Lorimer; Berna, Chantal; Ploner, Markus; Tracey, Irene

    2014-01-01

    The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings. PMID:25502237

  10. Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

    PubMed Central

    Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

    1989-01-01

    We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

  11. Visceral and somatic pain modalities reveal NaV1.7‐independent visceral nociceptive pathways

    PubMed Central

    Hockley, James R. F.; González‐Cano, Rafael; McMurray, Sheridan; Tejada‐Giraldez, Miguel A.; McGuire, Cian; Torres, Antonio; Wilbrey, Anna L.; Cibert‐Goton, Vincent; Nieto, Francisco R.; Pitcher, Thomas; Knowles, Charles H.; Baeyens, José Manuel; Wood, John N.; Winchester, Wendy J.; Bulmer, David C.; Cendán, Cruz Miguel

    2017-01-01

    Key points Voltage‐gated sodium channels play a fundamental role in determining neuronal excitability.Specifically, voltage‐gated sodium channel subtype NaV1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown.Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling.These results enable us to better understand the mechanisms underlying the transduction of noxious stimuli from the viscera, suggest that the investigation of pain pathways should be undertaken in a modality‐specific manner and help to direct drug discovery efforts towards novel visceral analgesics. Abstract Voltage‐gated sodium channel NaV1.7 is required for acute and inflammatory pain in mice and humans but its significance for visceral pain is unknown. Here we examine the role of NaV1.7 in visceral pain processing and the development of referred hyperalgesia using a conditional nociceptor‐specific NaV1.7 knockout mouse (NaV1.7Nav1.8) and selective small‐molecule NaV1.7 antagonist PF‐5198007. NaV1.7Nav1.8 mice showed normal nociceptive behaviours in response to intracolonic application of either capsaicin or mustard oil, stimuli known to evoke sustained nociceptor activity and sensitization following tissue damage, respectively. Normal responses following induction of cystitis by cyclophosphamide were also observed in both NaV1.7Nav1.8 and littermate controls. Loss, or blockade, of NaV1.7 did not affect afferent responses to noxious mechanical and chemical stimuli in nerve–gut preparations in mouse, or following antagonism of NaV1.7 in resected human appendix stimulated by noxious distending pressures. However, expression analysis of voltage‐gated sodium channel α subunits revealed NaV1.7 mRNA transcripts in nearly all retrogradely labelled colonic neurons, suggesting redundancy in function. By contrast, using comparative somatic behavioural models we identify that genetic deletion of NaV1.7 (in NaV1.8‐expressing neurons) regulates noxious heat pain threshold and that this can be recapitulated by the selective NaV1.7 antagonist PF‐5198007. Our data demonstrate that NaV1.7 (in NaV1.8‐expressing neurons) contributes to defined pain pathways in a modality‐dependent manner, modulating somatic noxious heat pain, but is not required for visceral pain processing, and advocate that pharmacological block of NaV1.7 alone in the viscera may be insufficient in targeting chronic visceral pain. PMID:28105664

  12. The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays.

    PubMed

    Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

    2016-08-01

    Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies.

  13. Increased γ-H2A.X intensity in response to chronic medium-dose-rate γ-ray irradiation.

    PubMed

    Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

    2012-01-01

    The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G(1) phase, although no significant difference was observed in G(2)/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G(1) phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G(1) phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation.

  14. Hypoechoic foci on EUS are simple and strong predictive factors for neoplastic gallbladder polyps.

    PubMed

    Cho, Jae Hee; Park, Jeong Youp; Kim, Yoon Jae; Kim, Hee Man; Kim, Hong Jeong; Hong, Sung Pil; Park, Seung Woo; Chung, Jae Bock; Song, Si Young; Bang, Seungmin

    2009-06-01

    EUS is an accurate imaging modality for delineating gallbladder (GB) structures; however, its clinical use in differentiating neoplastic GB polyps from nonneoplastic polyps is limited. Thus, we sought to characterize neoplastic GB polyps by analyzing unique EUS features. Our analysis revealed variably shaped, relatively hypoechoic portions in the core of polyps compared with general background echogenicity. Our purpose was to make a differential diagnosis between neoplastic and nonneoplastic GB polyps of less than 20 mm by use of EUS variables, including hypoechoic foci. Retrospective single-center study. University teaching hospital. Patients (n = 88) underwent preoperative EUS and cholecystectomy for GB polyps smaller than 20 mm. Hypoechoic foci were found in 30 of 33 patients (91%) with neoplastic polyps and 6 of 55 (11%) with nonneoplastic polyps. In a multivariate analysis, hypoechoic foci were the only significant predictive factor for neoplastic polyps (odds ratio [OR] 55.4, 95% CI, 8.26-371, P < .001); the sensitivity and specificity were 90% and 89%, respectively. In addition, polyps >15 mm had an increased risk of malignancy (OR 21.7, 95% CI, 2.35-201, P = .007), as did those with hypoechoic foci (OR 10.9; 95% CI, 1.01-117, P = .049). Retrospective review of selected patients from a tertiary medical center. The presence of hypoechoic foci on EUS is a strong predictive factor for neoplastic polyps. EUS may be useful in developing a treatment strategy for GB polyps.

  15. Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease.

    PubMed

    Soul, Janet S; Robertson, Richard L; Wypij, David; Bellinger, David C; Visconti, Karen J; du Plessis, Adré J; Kussman, Barry D; Scoppettuolo, Lisa A; Pigula, Frank; Jonas, Richard A; Newburger, Jane W

    2009-08-01

    Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%). Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

  16. An investigation into the inhibitory function of serotonin in diffuse noxious inhibitory controls in the neuropathic rat.

    PubMed

    Bannister, K; Lockwood, S; Goncalves, L; Patel, R; Dickenson, A H

    2017-04-01

    Following neuropathy α2-adrenoceptor-mediated diffuse noxious inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5-HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated actions predominate. Using in vivo electrophysiology we recorded WDR neuronal responses to von frey filaments applied to the hind paw before, and concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane-anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR neuronal firing in the presence of conditioning stimulus and was investigated in SNL rats following spinal application of (1) selective serotonin reuptake inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus 5-HT7 receptor antagonist SB269970, or (3) SSRI plus α2 adrenoceptor antagonist atipamezole. DNIC were revealed in SNL animals following spinal application of SSRI, but this effect was abolished upon joint application of SSRI plus SB269970 or atipamezole. We propose that in SNL animals the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT (presumed present following application of SSRI) were mediated via 5-HT7 receptors. The anti-nociception depends upon an underlying tonic noradrenergic inhibitory tone via the α2-adrenoceptor. Following neuropathy enhanced spinal serotonin availability switches the predominant spinal 5-HT receptor-mediated actions but also alters noradrenergic signalling. We highlight the therapeutic complexity of SSRIs and monoamine modulators for the treatment of neuropathic pain. © 2016 European Pain Federation - EFIC®.

  17. Noxious lingual stimulation influences the excitability of the face primary motor cerebral cortex (face MI) in the rat.

    PubMed

    Adachi, K; Murray, G M; Lee, J-C; Sessle, B J

    2008-09-01

    The mechanisms whereby orofacial pain affects motor function are poorly understood. The aims were to determine whether 1) lingual algesic chemical stimulation affected face primary motor cerebral cortex (face MI) excitability defined by intracortical microstimulation (ICMS); and 2) any such effects were limited to the motor efferent MI zones driving muscles in the vicinity of the noxious stimulus. Ketamine-anesthetized Sprague-Dawley male rats were implanted with electromyographic (EMG) electrodes into anterior digastric, masseter, and genioglossus muscles. In 38 rats, three microelectrodes were located in left face MI at ICMS-defined sites for evoking digastric and/or genioglossus responses. ICMS thresholds for evoking EMG activity from each site were determined every 15 min for 1 h, then the right anterior tongue was infused (20 microl, 120 microl/h) with glutamate (1.0 M, n = 18) or isotonic saline (n = 7). Subsequently, ICMS thresholds were determined every 15 min for 4 h. In intact control rats (n = 13), ICMS thresholds were recorded over 5 h. Only left and right genioglossus ICMS thresholds were significantly increased (< or =350%) in the glutamate infusion group compared with intact and isotonic saline groups (P < 0.05). These dramatic effects of glutamate on ICMS-evoked genioglossus activity contrast with its weak effects only on right genioglossus activity evoked from the internal capsule or hypoglossal nucleus. This is the first documentation that intraoral noxious stimulation results in prolonged neuroplastic changes manifested as a decrease in face MI excitability. These changes appear to occur predominantly in those parts of face MI that provide motor output to the orofacial region receiving the noxious stimulation.

  18. Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations.

    PubMed

    Bannister, Kirsty; Patel, Ryan; Goncalves, Leonor; Townson, Louisa; Dickenson, Anthony H

    2015-09-01

    Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals. Spinal nerve ligation was the model of neuropathy. Diffuse noxious inhibitory control was present in control rats but abolished after neuropathy. α2 adrenoceptor mechanisms underlie DNIC because the antagonists, yohimbine and atipamezole, markedly attenuated this descending inhibition. We restored DNIC in spinal nerve ligated animals by blocking 5-HT3 descending facilitations with the antagonist ondansetron or by enhancing norepinephrine modulation through the use of reboxetine (a norepinephrine reuptake inhibitor, NRI) or tapentadol (μ-opioid receptor agonist and NRI). Additionally, ondansetron enhanced DNIC in normal animals. Diffuse noxious inhibitory controls are reduced after peripheral nerve injury illustrating the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions. Underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and the use of tapentadol and duloxetine (a serotonin, NRI) in patients. We suggest that pharmacological strategies through manipulation of the monoamine system could be used to enhance DNIC in patients by blocking descending facilitations with ondansetron or enhancing norepinephrine inhibitions, so possibly reducing chronic pain.

  19. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin

    PubMed Central

    Dickenson, Anthony H.

    2016-01-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a “WDR phenotype.” After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. PMID:27098028

  20. Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

    PubMed

    Patel, Ryan; Dickenson, Anthony H

    2016-07-01

    Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

  1. Blockade of opioid receptors in the medullary reticularis nucleus dorsalis, but not the rostral ventromedial medulla, prevents analgesia produced by diffuse noxious inhibitory control in rats with muscle inflammation.

    PubMed

    de Resende, Marcos A; Silva, Luis Felipe S; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A

    2011-06-01

    Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45 °C and 47 °C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. The current study shows that DNIC activates opioid receptors in the MdD, but not the RVM, to produce analgesia. These data are important for understanding clinical studies on DNIC as well as for potential treatment of chronic pain patients. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

  2. Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials.

    PubMed

    Franz, Marcel; Nickel, Moritz M; Ritter, Alexander; Miltner, Wolfgang H R; Weiss, Thomas

    2015-04-01

    Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention. Copyright © 2015 the American Physiological Society.

  3. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

    PubMed

    Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

    2008-08-15

    Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

  4. Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study.

    PubMed

    Tracy, Lincoln M; Labuschagne, Izelle; Georgiou-Karistianis, Nellie; Gibson, Stephen J; Giummarra, Melita J

    2017-09-01

    Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants attended two sessions, self-administering intranasal oxytocin (24 IU) in one session, and placebo in another. Participants rated intensity and unpleasantness of thermal heat stimuli at three body sites: the cervical spine, deltoid, and tibialis anterior, on 11-point numerical rating scales. Compared with placebo, intranasal oxytocin increased the perceived intensity of noxious heat stimuli in women with CNSP (Cohen's d=0.71), but not in men with CNSP, or healthy, pain-free controls. Men and women displayed divergent sensitivity across target sites for ratings of pain intensity (partial eta squared=0.12) and pain unpleasantness (partial eta squared=0.24), irrespective of drug condition. Men were more sensitive at the cervical spine and deltoid, whereas women were more sensitive at the tibialis. These findings suggest that oxytocin and endogenous sex hormones may interact to influence the salience of noxious stimuli. The hyperalgesic effects of oxytocin in women suggest that caution should be taken when considering oxytocin in the management of chronic pain. CT-2016-CTN-01313-1; ACTRN12616000532404. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  5. Noxious mechanical heterotopic stimulation induces inhibition of the spinal dorsal horn neuronal network: analysis of spinal somatosensory-evoked potentials.

    PubMed

    Meléndez-Gallardo, J; Eblen-Zajjur, A

    2016-09-01

    Most of the endogenous pain modulation (EPM) involves the spinal dorsal horn (SDH). EPM including diffuse noxious inhibitory controls have been extensively described in oligoneuronal electrophysiological recordings but less attention had been paid to responses of the SDH neuronal population to heterotopic noxious stimulation (HNS). Spinal somatosensory-evoked potentials (SEP) offer the possibility to evaluate the neuronal network behavior, reflecting the incoming afferent volleys along the entry root, SDH interneuron activities and the primary afferent depolarization. SEP from de lumbar cord dorsum were evaluated during mechanical heterotopic noxious stimuli. Sprague-Dawley rats (n = 12) were Laminectomized (T10-L3). The sural nerve of the left hind paw was electrically stimulated (5 mA, 0.5 ms, 0.05 Hz) to induce lumbar SEP. The HNS (mechanic clamp) was applied sequentially to the tail, right hind paw, right forepaw, muzzle and left forepaw during sural stimulation. N wave amplitude decreases (-16.6 %) compared to control conditions when HNS was applied to all areas of stimulation. This effect was more intense for muzzle stimulation (-23.5 %). N wave duration also decreased by -23.6 %. HNS did not change neither the amplitude nor the duration of the P wave but dramatically increases the dispersion of these two parameters. The results of the present study strongly suggest that a HNS applied to different parts of the body is able to reduce the integrated electrical response of the SDH, suggesting that not only wide dynamic range neurons but many others in the SDH are modulated by the EPM.

  6. Internal validity of inter-digital web pinching as a model for perceptual diffuse noxious inhibitory controls-induced hypoalgesia in healthy humans.

    PubMed

    Streff, Anouk; Michaux, Gilles; Anton, Fernand

    2011-01-01

    Hot and ice-water immersions are commonly used for heterotopic noxious counter-stimulation (HNCS) in investigations on endogenous pain modulation. However, coincident sympathetic thermoregulatory activity does not allow to differentiate between perceptual hypoalgesia related to baroreflex sensitivity (BRS) or diffuse noxious inhibitory controls (DNIC). The present study analysed the internal validity of another supposedly less confounded tonic pain model (inter-digital web pinching; IWP) regarding its potential as DNIC trigger. We performed a randomized controlled study in 24 healthy gender-matched drug-free volunteers aged 21-54 (median 25) years. The study protocol comprised the assessment of mechanical and thermal perceptual wind-up before and after an IWP (15N) or hot water immersion trial (HIT; 47.5°C) of 2 min duration. Wind-up was induced either by 10 repetitive (1Hz) contact heat (max. 49°C; 5×5 mm thermode) or ballistic impact stimuli (0.5g at 9 m/s) on the phalanges of the non-dominant hand. Cardiovascular activity, pain experience and corrugator muscle activity were continuously monitored. Although both HNCS forms produced a similar pain experience (45% of scale), a more pronounced cardiovascular activity was observable for the HIT (P<0.01). This indicates a higher baroreceptor activity and stronger contamination of painful water immersion by BRS-related hypoalgesia. Regardless of pain modality, wind-up was significantly reduced by HNCS, although this was stronger for painful water immersion than for noxious pinching (P<0.01). The HNCS types allow a differentiation between BRS-related and DNIC-like hypoalgesia. IWP proved its validity for DNIC induction, being practically non-confounded by BRS. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  7. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    PubMed

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

  8. Acute Noxious Stimulation Modifies Morphine Effect in Serotonergic but not Dopaminergic Midbrain Areas

    PubMed Central

    Bajic, Dusica; Commons, Kathryn G.

    2010-01-01

    It is poorly understood if and how pain may modify the effect of opioids on neural systems that contribute to reward and addictive behavior. We hypothesized that the activation of ascending dopaminergic and serotonergic nuclei by morphine is modified by the presence of noxious stimulation. Immunohistochemical double-labeling technique with Fos was used to examine if an intraplantar formalin injection, an acute noxious input, changed the effect of morphine on dopaminergic neurons of the ventral tegmental area (VTA), and serotonergic neurons of the dorsal raphe nucleus (DR). Four groups of rats were analyzed: (1) CONTROL injected with normal saline subcutaneously, (2) rats treated with FORMALIN into the hind paw 30 minutes after normal saline injection, (3) rats injected with MORPHINE sulfate subcutaneously, and (4) rats treated with formalin into the hind paw 30 minutes after morphine injection (MORPHINE/FORMALIN). Following morphine injection, there was an increase in the number of dopaminergic neurons in the VTA with Fos immunolabeling. However, noxious stimulation did not detectably change morphine's effect on Fos expression in VTA dopamine neurons. In contrast, the number of serotonergic neurons containing Fos was increased in the morphine/formalin group compared to all other groups and this effect was topographically selective for the dorsal area of the DR at mid rostro-caudal levels. Therefore, morphine's activation of the VTA, which is associated with motivated behavior and reward seeking, appears similar in the context of pain. However, activation of the ascending serotonin system, which influences mood and has the capacity to modify reward pathways, appears different. In addition, these findings reveal interactions between nociceptive signaling and opioids that contrasts with the notion that opioids simply block access of nociceptive signaling to supraspinal structures. PMID:20026253

  9. Opiates Modulate Noxious Chemical Nociception through a Complex Monoaminergic/Peptidergic Cascade

    PubMed Central

    Mills, Holly; Ortega, Amanda; Law, Wenjing; Hapiak, Vera; Summers, Philip; Clark, Tobias

    2016-01-01

    The ability to detect noxious stimuli, process the nociceptive signal, and elicit an appropriate behavioral response is essential for survival. In Caenorhabditis elegans, opioid receptor agonists, such as morphine, mimic serotonin, and suppress the overall withdrawal from noxious stimuli through a pathway requiring the opioid-like receptor, NPR-17. This serotonin- or morphine-dependent modulation can be rescued in npr-17-null animals by the expression of npr-17 or a human κ opioid receptor in the two ASI sensory neurons, with ASI opioid signaling selectively inhibiting ASI neuropeptide release. Serotonergic modulation requires peptides encoded by both nlp-3 and nlp-24, and either nlp-3 or nlp-24 overexpression mimics morphine and suppresses withdrawal. Peptides encoded by nlp-3 act differentially, with only NLP-3.3 mimicking morphine, whereas other nlp-3 peptides antagonize NLP-3.3 modulation. Together, these results demonstrate that opiates modulate nociception in Caenorhabditis elegans through a complex monoaminergic/peptidergic cascade, and suggest that this model may be useful for dissecting opiate signaling in mammals. SIGNIFICANCE STATEMENT Opiates are used extensively to treat chronic pain. In Caenorhabditis elegans, opioid receptor agonists suppress the overall withdrawal from noxious chemical stimuli through a pathway requiring an opioid-like receptor and two distinct neuropeptide-encoding genes, with individual peptides from the same gene functioning antagonistically to modulate nociception. Endogenous opioid signaling functions as part of a complex, monoaminergic/peptidergic signaling cascade and appears to selectively inhibit neuropeptide release, mediated by a α-adrenergic-like receptor, from two sensory neurons. Importantly, receptor null animals can be rescued by the expression of the human κ opioid receptor, and injection of human opioid receptor ligands mimics exogenous opiates, highlighting the utility of this model for dissecting opiate signaling in mammals. PMID:27194330

  10. Rise to SUMMIT: the Sydney University Multiple-Mirror Telescope

    NASA Astrophysics Data System (ADS)

    Moore, Anna M.; Davis, John

    2000-07-01

    The Sydney University Multiple Mirror Telescope (SUMMIT) is a medium-sized telescope designed specifically for high resolution stellar spectroscopy. Throughout the design emphasis has been placed on high efficiency at low cost. The telescope consists of four 0.46 m diameter mirrors mounted on a single welded steel frame. Specially designed mirror cells support and point each mirror, allowing accurate positioning of the images on optical fibers located at the foci of the mirrors. Four fibers convey the light to the future location of a high resolution spectrograph away from the telescope in a stable environment. An overview of the commissioning of the telescope is presented, including the guidance and automatic mirror alignment and focussing systems. SUMMIT is located alongside the Sydney University Stellar Interferometer at the Paul Wild Observatory, near Narrabri, Northern New South Wales.

  11. Effects of the Inter-Parental Relationship on Adolescents’ Emotional Security and Adjustment: The Important Role of Fathers

    PubMed Central

    Suh, Go Woon; Fabricius, William V.; Stevenson, Matthew M.; Parke, Ross D.; Cookston, Jeffrey T.; Braver, Sanford L.; Saenz, Delia S.

    2016-01-01

    We examined the mediational roles of multiple types of adolescents’ emotional security in relations between multiple aspects of the inter-parental relationship and adolescents’ mental health from ages 13 to 16 (N = 392). General marital quality, non-violent parent conflict, and physical intimate partner violence independently predicted mental health. Security in the father-adolescent relationship, over and above security with the mother and security in regard to parent conflict, mediated the link from general marital quality to adolescents’ mental health. With two exceptions, paths were stable for boys and girls, biological- and step-fathers, and Anglo- and Mexican-Americans. The findings reveal the need to expand the traditional foci on parent conflict and relationships with mothers to include general marital quality and relationships with fathers. PMID:27690497

  12. Effects of the interparental relationship on adolescents' emotional security and adjustment: The important role of fathers.

    PubMed

    Suh, Go Woon; Fabricius, William V; Stevenson, Matthew M; Parke, Ross D; Cookston, Jeffrey T; Braver, Sanford L; Saenz, Delia S

    2016-10-01

    We examined the mediational roles of multiple types of adolescents' emotional security in relations between multiple aspects of the interparental relationship and adolescents' mental health from ages 13 to 16 (N = 392). General marital quality, nonviolent parent conflict, and physical intimate partner violence independently predicted mental health. Security in the father-adolescent relationship, over and above security with the mother and security in regard to parent conflict, mediated the link from general marital quality to adolescents' mental health. With 2 exceptions, paths were stable for boys and girls, biological- and stepfathers, and Anglo- and Mexican Americans. The findings reveal the need to expand the traditional foci on parent conflict and relationships with mothers to include general marital quality and relationships with fathers. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Sprayable enzyme-activatable fluorescent probes: kinetic mapping using dynamic fluorescence imaging can help detecting tiny cancer foci (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kobayashi, Hisataka

    2017-02-01

    Optical fluorescence-guided imaging is increasingly used to guide surgery and endoscopic procedures. Sprayable enzyme-activatable probes are particularly useful because of high target-to-background ratios that increase sensitivity for tiny cancer foci. However, green fluorescent activatable probes suffers from interference from autofluorescence found in biological tissue. Dynamic imaging followed by the kinetic analysis could be detected local enzyme activity and used to differentiate specific fluorescence arising from an activated probe in a tumor from autofluorescence in background tissues especially when low concentrations of the dye are applied to detect tiny cancer foci. Serial fluorescence imaging was performed using various concentrations of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) which was sprayed on the peritoneal surface with tiny implants of SHIN3-dsRed ovarian cancer tumors. Temporal differences in signal between specific green fluorescence in cancer foci and non-specific autofluorescence in background tissue was measured and processed into three kinetic maps reflecting maximum fluorescence signal (MF), wash-in rate (WIR), and area under the curve (AUC), respectively. Especially at lower concentrations, kinetic maps derived from dynamic fluorescence imaging were clearly superior to unprocessed images for detection small cancer foci.

  14. The Focinator v2-0 - Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification.

    PubMed

    Oeck, Sebastian; Malewicz, Nathalie M; Hurst, Sebastian; Al-Refae, Klaudia; Krysztofiak, Adam; Jendrossek, Verena

    2017-07-01

    The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci. The refined software is now even more user-friendly due to a graphical interface and further features. Thus, we included an R-script-based mode for automated image opening, file naming, progress monitoring and an error report. Consequently, the evaluation no longer required the attendance of the operator after initial parameter definition. Moreover, the Focinator v2-0 is now able to perform multi-channel analysis of four channels and evaluation of protein-protein colocalization by comparison of up to three foci channels. This enables for example the quantification of foci in cells of a specific cell cycle phase.

  15. Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

    PubMed Central

    Lee, Youn-Bok; Chen, Han-Jou; Peres, João N.; Gomez-Deza, Jorge; Attig, Jan; Štalekar, Maja; Troakes, Claire; Nishimura, Agnes L.; Scotter, Emma L.; Vance, Caroline; Adachi, Yoshitsugu; Sardone, Valentina; Miller, Jack W.; Smith, Bradley N.; Gallo, Jean-Marc; Ule, Jernej; Hirth, Frank; Rogelj, Boris; Houart, Corinne; Shaw, Christopher E.

    2013-01-01

    Summary The GGGGCC (G4C2) intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration. PMID:24290757

  16. The generalized mean zone plate

    NASA Astrophysics Data System (ADS)

    Xia, Tian; Cheng, Shubo; Tao, Shaohua

    2018-06-01

    In this paper a generalized mean zone plate is proposed, which generates twin foci located at the positions satisfying the expression of the generalized mean, which includes the m-golden mean, precious mean, and so on. The generalized mean zone plate can be designed to generate twin foci with various position ratios. The diffraction properties of the generalized mean zone plates have been investigated with simulations and experiments. The results show that the ratio of the positions of the twin foci for the generalized mean zone plate can be designed with the selected zone plate parameters.

  17. [A case of multiple cavernous angioma with dementia].

    PubMed

    Kariya, S; Kawahara, M; Suzumura, A

    2000-10-01

    We reported a 65-year-old man who developed dementia since 50 years of age. His consciousness was clear but he was indifferent to his illness. Also, the luck of attention was recognized when we underwent examinations and the result of intellectual test varied every time we performed. His memory function was almost normal on the examination which was performed when he was cooperative. Magnetic resonance imaging (MRI) disclosed multiple tiny lesions (more than 130 in all) in cerebrum, brainstem, cerebellum and spinal cord. These lesions were compatible with multiple cavernous angioma. Most of lesions manifested high-density area on cranial CT. Though the multiplicity of foci indicated the possibility of familial occurrence, he was considered to be a sporadic case on his lineage investigation and the brain MRI of his only son. In this case, neither headache nor seizures which were known as the major clinical features of intracerebral cavernous angioma was observed. He was diagnosed as having white matter dementia characterized by attentional dysfunction, decrement of volition and less memory disturbance. We speculated that he developed symptomatic dementia by the sum of multiple minor degeneration, especially in frontal lobe white matter, caused by repeated minor bleeding from cavernous angiomas.

  18. Breast cancer risk by extent and type of atypical hyperplasia: An update from the Nurses' Health Studies.

    PubMed

    Collins, Laura C; Aroner, Sarah A; Connolly, James L; Colditz, Graham A; Schnitt, Stuart J; Tamimi, Rulla M

    2016-02-15

    Women with atypical hyperplasia (AH) on a benign breast biopsy specimen are at increased risk for the development of breast cancer. However, the relation between the type and extent of AH (atypical ductal hyperplasia [ADH] vs atypical lobular hyperplasia [ALH]) and the magnitude of the breast cancer risk is not well defined. A nested case-control study of benign breast disease and breast cancer risk was conducted. Women with breast cancer and prior benign breast biopsy findings (488 cases) were matched to women with prior benign breast biopsy findings who were free from breast cancer (1907 controls). Benign breast biopsy slides were reviewed and categorized as nonproliferative, proliferative without atypia, or AH (ADH or ALH). The number of foci of AH was also recorded. Among women with ADH, the interrelation between the extent of atypia and breast cancer risk was not significant (odds ratio [OR] for 1 or 2 foci, 3.5; 95% confidence interval [CI], 2.2-5.6; OR for ≥3 foci, 2.7; 95% CI, 1.4-5.1; P = .41). Similarly, although the risk with ALH was higher for those with ≥3 foci than for those with <3 foci, the difference was not statistically significant (OR for 1 or 2 foci, 5.2; 95% CI, 2.7-10.0; OR for ≥3 foci, 8.0; 95% CI, 4.5-14.2; P = .19). This analysis demonstrates that the extent of ADH or ALH does not significantly contribute to breast cancer risk. The lack of a significant dose-response relation between the extent and type of atypia and breast cancer risk suggests that it would be premature to use the extent of atypia to influence management decisions for women with ADH or ALH. © 2015 American Cancer Society.

  19. Acute pyelonephritis in transplanted kidneys: can diffusion-weighted magnetic resonance imaging be useful for diagnosis and follow-up?

    PubMed

    Faletti, Riccardo; Cassinis, Maria Carla; Gatti, Marco; Giglio, Jacopo; Guarnaccia, Carla; Messina, Marina; Bergamasco, Laura; Fonio, Paolo

    2016-03-01

    To assess reliability of diffusion-weighted magnetic resonance imaging (DW-MRI) in the management of acute pyelonephritis (APN) foci in transplanted kidneys. In the 2012-2014 period, 24 kidney-transplanted patients underwent MR screening for clinical suspicion of APN. Two readers independently analyzed all images, establishing presence and location of APN foci. The 22 patients who were positive at the MR exam constituted the study population. For each patient the apparent diffusion coefficient (ADC) was measured in the APN foci and in three sites of the healthy parenchyma (case-control comparison). The data were matched to the laboratory measurements for white blood cell, C-reactive protein, and serum creatinine. Forty-six APN foci were found in 22/24 patients. At the acute stage, the difference in ADC between healthy parenchyma and APN foci was significant (2.06 ± 0.16 vs. 1.43 ± 0.32 × 10(-3) mm(2)/s; p < 0.0001). The performance of ADC as APN indicator was tested by the receiving operating characteristics (ROC) curve: the area under curve AUC = 0.99 witnessed an excellent discriminatory ability, with threshold APN/normal parenchyma 1.9 × 10(-3) mm(2)/s. At the 1-month follow-up 43/46 APN foci were no longer visible, with ADC values significantly higher than at the acute stage; all laboratory data were physiological, with WBC significantly reduced from the acute phase (5.2 ± 1.6 × 10(9)/L vs. 10.6 ± 4.8 × 10(9)/L; p < 0.0001). The other 3 patients underwent further therapy and exams, including a third MR. DW-MRI with ADC measurement seems to be a reliable tool in diagnosing and monitoring APN foci in transplanted kidneys, with clinical impact on patient management.

  20. The Postnatal Development of Spinal Sensory Processing

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Maria; Jennings, Ernest

    1999-07-01

    The mechanisms by which infants and children process pain should be viewed within the context of a developing sensory nervous system. The study of the neurophysiological properties and connectivity of sensory neurons in the developing spinal cord dorsal horn of the intact postnatal rat has shed light on the way in which the newborn central nervous system analyzes cutaneous innocuous and noxious stimuli. The receptive field properties and evoked activity of newborn dorsal horn cells to single repetitive and persistent innocuous and noxious inputs are developmentally regulated and reflect the maturation of excitatory transmission within the spinal cord. These changes will have an important influence on pain processing in the postnatal period.

  1. Forecasting system predicts presence of sea nettles in Chesapeake Bay

    NASA Astrophysics Data System (ADS)

    Brown, Christopher W.; Hood, Raleigh R.; Li, Zhen; Decker, Mary Beth; Gross, Thomas F.; Purcell, Jennifer E.; Wang, Harry V.

    Outbreaks of noxious biota, which occur in both aquatic and terrestrial systems, can have considerable negative economic impacts. For example, an increasing frequency of harmful algal blooms worldwide has negatively affected the tourism industry in many regions. Such impacts could be mitigated if the conditions that give rise to these outbreaks were known and could be monitored. Recent advances in technology and communications allow us to continuously measure and model many environmental factors that are responsible for outbreaks of certain noxious organisms. A new prototype ecological forecasting system predicts the likelihood of occurrence of the sea nettle (Chrysaora quinquecirrha), a stinging jellyfish, in the Chesapeake Bay.

  2. Federal Interagency Coordination for Invasive Plant Issues -- The Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW)

    USGS Publications Warehouse

    Westbrooks, Randy G.

    2011-01-01

    The U.S. Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW) is a formal partnership between 16 federal agencies that have invasive plant management and regulatory responsibilities for the United States and its territories. Efforts to develop a national level federal interagency committee to coordinate federal activities were initiated by national weed program managers with the USDA Forest Service and the Bureau of Land Management in 1989. FICMNEW was formally established through a Memorandum of Understanding that was signed by agency administrators of member agencies in August, 1994.

  3. Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex activity of the hamstring muscle in rats: possible implications of neuronal mechanisms in the development of tight hamstrings in lumbar disc herniation.

    PubMed

    Hirayama, Jiro; Yamagata, Masatsune; Takahashi, Kazuhisa; Moriya, Hideshige

    2005-05-01

    The effect of noxious electrical stimulation of the peroneal nerve on the stretch reflex electromyogram activity of the hamstring muscle (semitendinous) was studied. To verify the following hypothetical mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex muscle activity of hamstrings is increased by painful inputs from an injured spinal nerve root and the increased stretch reflex muscle activity is maintained by central sensitization. It is reported that stretch reflex activity of the trunk muscles is induced by noxious stimulation of the sciatic nerve and maintained by central sensitization. In spinalized rats (transected spinal cord), the peroneal nerve was stimulated electrically as a conditioning stimulus. Stretch reflex electromyogram activity of the semitendinous muscle was recorded before and after the conditioning stimulus. Even after electrical stimulation was terminated, an increased stretch reflex activity of the hamstring muscle was observed. It is likely that a central sensitization mechanism at the spinal cord level was involved in the increased reflex activity. Central sensitization may play a part in the neuronal mechanisms of tight hamstrings in lumbar disc herniation.

  4. Sensing the heat with TRPM3.

    PubMed

    Vriens, Joris; Voets, Thomas

    2018-05-01

    Heat sensation, the ability to detect warm and noxious temperatures, is an ancient and indispensable sensory process. Noxious temperatures can have detrimental effects on the physiology and integrity of cells, and therefore, the detection of environmental hot temperatures is absolutely crucial for survival. Temperature-sensitive ion channels, which conduct ions in a highly temperature-dependent manner, have been put forward as molecular thermometers expressed at the endings of sensory neurons. In particular, several temperature-sensitive members of the transient receptor potential (TRP) superfamily of ion channels have been identified, and a multitude of in vivo studies have shown that the capsaicin-sensitive TRPV1 channel plays a key role as a noxious heat sensor. However, Trpv1-deficient mice display a residual heat sensitivity suggesting the existence of additional heat sensor(s). In this chapter, we provide evidence for the role of the non-selective calcium-permeable TRPM3 ion channel as an additional heat sensor that acts independently of TRPV1, and give an update of the modulation of this channel by various molecular mechanisms. Finally, we compare antagonists of TRPM3 to specific blockers of TRPV1 as potential analgesic drugs to treat pathological pain.

  5. Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight.

    PubMed

    Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W; Frye, Mark A

    2012-08-15

    Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously 'anti-track' the noxious source.

  6. Flies dynamically anti-track, rather than ballistically escape, aversive odor during flight

    PubMed Central

    Wasserman, Sara; Lu, Patrick; Aptekar, Jacob W.; Frye, Mark A.

    2012-01-01

    SUMMARY Tracking distant odor sources is crucial to foraging, courtship and reproductive success for many animals including fish, flies and birds. Upon encountering a chemical plume in flight, Drosophila melanogaster integrates the spatial intensity gradient and temporal fluctuations over the two antennae, while simultaneously reducing the amplitude and frequency of rapid steering maneuvers, stabilizing the flight vector. There are infinite escape vectors away from a noxious source, in contrast to a single best tracking vector towards an attractive source. Attractive and aversive odors are segregated into parallel neuronal pathways in flies; therefore, the behavioral algorithms for avoidance may be categorically different from tracking. Do flies plot random ballistic or otherwise variable escape vectors? Or do they instead make use of temporally dynamic mechanisms for continuously and directly avoiding noxious odors in a manner similar to tracking appetitive ones? We examine this question using a magnetic tether flight simulator that permits free yaw movements, such that flies can actively orient within spatially defined odor plumes. We show that in-flight aversive flight behavior shares all of the key features of attraction such that flies continuously ‘anti-track’ the noxious source. PMID:22837456

  7. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases.

    PubMed

    Bessac, Bret F; Sivula, Michael; von Hehn, Christian A; Caceres, Ana I; Escalera, Jasmine; Jordt, Sven-Eric

    2009-04-01

    The release of methyl isocyanate in Bhopal, India, caused the worst industrial accident in history. Exposures to industrial isocyanates induce lacrimation, pain, airway irritation, and edema. Similar responses are elicited by chemicals used as tear gases. Despite frequent exposures, the biological targets of isocyanates and tear gases in vivo have not been identified, precluding the development of effective countermeasures. We use Ca(2+) imaging and electrophysiology to show that the noxious effects of isocyanates and those of all major tear gas agents are caused by activation of Ca(2+) influx and membrane currents in mustard oil-sensitive sensory neurons. These responses are mediated by transient receptor potential ankyrin 1 (TRPA1), an ion channel serving as a detector for reactive chemicals. In mice, genetic ablation or pharmacological inhibition of TRPA1 dramatically reduces isocyanate- and tear gas-induced nocifensive behavior after both ocular and cutaneous exposures. We conclude that isocyanates and tear gas agents target the same neuronal receptor, TRPA1. Treatment with TRPA1 antagonists may prevent and alleviate chemical irritation of the eyes, skin, and airways and reduce the adverse health effects of exposures to a wide range of toxic noxious chemicals.

  8. Multi-modal pain measurements in infants

    PubMed Central

    Worley, A.; Fabrizi, L.; Boyd, S.; Slater, R.

    2012-01-01

    A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n = 6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. PMID:22285660

  9. Multi-modal pain measurements in infants.

    PubMed

    Worley, A; Fabrizi, L; Boyd, S; Slater, R

    2012-04-15

    A non-invasive integrated method was developed to measure neural and behavioural responses to peripheral sensory and noxious stimulation in human infants. The introduction of a novel event-detection interface allows synchronous recording of: (i) muscle and central nervous system activity with surface electromyography (EMG), scalp electroencephalography (EEG) and near-infrared spectroscopy (NIRS); (ii) behavioural responses with video-recording and (iii) autonomic responses (heart rate, oxygen saturation, respiratory rate and cardiovascular activity) with electrocardiography (ECG) and pulse oximetry. The system can detect noxious heel lance and touch stimuli with precision (33 μs and 624 μs respectively) and accuracy (523 μs and 256 μs) and has 100% sensitivity and specificity for both types of stimulation. Its ability to detect response latencies accurately was demonstrated by a shift in latency of the vertex potential of 20.7 ± 15.7 ms (n=6 infants), following touch of the heel and of the shoulder, reflecting the distance between the two sites. This integrated system has provided reliable and reproducible measurements of responses to sensory and noxious stimulation in human infants on more than 100 test occasions. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Plague Outbreak in Libya, 2009, Unrelated to Plague in Algeria

    PubMed Central

    Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric

    2013-01-01

    After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci. PMID:23347743

  11. Understanding the Persistence of Plague Foci in Madagascar

    PubMed Central

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-01-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar. PMID:24244760

  12. Plague outbreak in Libya, 2009, unrelated to plague in Algeria.

    PubMed

    Cabanel, Nicolas; Leclercq, Alexandre; Chenal-Francisque, Viviane; Annajar, Badereddin; Rajerison, Minoarisoa; Bekkhoucha, Souad; Bertherat, Eric; Carniel, Elisabeth

    2013-02-01

    After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci.

  13. Understanding the persistence of plague foci in Madagascar.

    PubMed

    Andrianaivoarimanana, Voahangy; Kreppel, Katharina; Elissa, Nohal; Duplantier, Jean-Marc; Carniel, Elisabeth; Rajerison, Minoarisoa; Jambou, Ronan

    2013-11-01

    Plague, a zoonosis caused by Yersinia pestis, is still found in Africa, Asia, and the Americas. Madagascar reports almost one third of the cases worldwide. Y. pestis can be encountered in three very different types of foci: urban, rural, and sylvatic. Flea vector and wild rodent host population dynamics are tightly correlated with modulation of climatic conditions, an association that could be crucial for both the maintenance of foci and human plague epidemics. The black rat Rattus rattus, the main host of Y. pestis in Madagascar, is found to exhibit high resistance to plague in endemic areas, opposing the concept of high mortality rates among rats exposed to the infection. Also, endemic fleas could play an essential role in maintenance of the foci. This review discusses recent advances in the understanding of the role of these factors as well as human behavior in the persistence of plague in Madagascar.

  14. Genomic Surveillance Elucidates Persistent Wild Poliovirus Transmission During 2013-2015 in Major Reservoir Areas of Pakistan.

    PubMed

    Alam, Muhammad Masroor; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan; Rehman, Lubna; Zaidi, Syed Sohail Zahoor

    2016-01-15

    Despite tremendous efforts in the fight against polio, Pakistan bears the highest proportion of poliomyelitis cases among the 3 endemic countries including Afghanistan and Nigeria. Apart from insecurity and inaccessibility challenges, the substantial shift of unimmunized children from North Waziristan due to recent military operations was presumed to favor the widespread poliovirus infection in Pakistan. To better understand the current epidemiological situation, we analyzed the virologic data of wild poliovirus type 1 (WPV1) strains detected in Pakistan during 2013-2015. Five genetic clusters (A-E) were identified with at least 5% nucleotide divergence in the viral protein 1 (VP1) coding region. Peshawar, Quetta, and Karachi were found to be the major endemic foci where multiple discrete genetic lineages of WPV1 were detected. Phylogenetic analysis suggests that wild poliovirus strains from endemic regions were genetically distant (with 5%-15% VP1 nucleotide divergence) from those detected in North Waziristan cases, excluding the possibility of a recent progenitor of WPV1 instigating single-source transmission across the country. Orphan lineages detected in Rawalpindi, Lahore, Hyderabad, Sukkur, and Jacobabad revealed silent transmission and the need for vigilant surveillance. Sustenance of analogous genetic lineages over a period of 3 years highlights multiple unimmunized foci present to maintain viral genetic diversity. Our findings are inconsistent with the hypothesis that impoverished populations from North Waziristan serve as a possible determinant of widespread poliomyelitis infection in Pakistan and further emphasize the need to scale-up clinical and environmental surveillance as well as immunization activities. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. Inhibition of exportin-1 function results in rapid cell cycle-associated DNA damage in cancer cells

    PubMed Central

    Burke, Russell T.; Marcus, Joshua M.; Orth, James D.

    2017-01-01

    Selective inhibitors of nuclear export (SINE) are small molecules in development as anti-cancer agents. The first-in-class SINE, selinexor, is in clinical trials for blood and solid cancers. Selinexor forms a covalent bond with exportin-1 at cysteine-528, and blocks its ability to export cargos. Previous work has shown strong cell cycle effects and drug-induced cell death across many different cancer-derived cell lines. Here, we report strong cell cycle-associated DNA double-stranded break formation upon the treatment of cancer cells with SINE. In multiple cell models, selinexor treatment results in the formation of clustered DNA damage foci in 30-40% of cells within 8 hours that is dependent upon cysteine-528. DNA damage strongly correlates with G1/S-phase and decreased DNA replication. Live cell microscopy reveals an association between DNA damage and cell fate. Cells that form damage in G1-phase more often die or arrest, while those damaged in S/G2-phase frequently progress to cell division. Up to half of all treated cells form damage foci, and most cells that die after being damaged, were damaged in G1-phase. By comparison, non-transformed cell lines show strong cell cycle effects but little DNA damage and less death than cancer cells. Significant drug combination effects occur when selinexor is paired with different classes of agents that either cause DNA damage or that diminish DNA damage repair. These data present a novel effect of exportin-1 inhibition and provide a strong rationale for multiple combination treatments of selinexor with agents that are currently in use for the treatment of different solid cancers. PMID:28467801

  16. Subtle Hemorrhagic Brain Injury is Associated with Neurodevelopmental Impairment in Infants with Repaired Congenital Heart Disease

    PubMed Central

    Soul, Janet S.; Robertson, Richard L.; Wypij, David; Bellinger, David C.; Visconti, Karen J.; du Plessis, Adré J.; Kussman, Barry D.; Scoppettuolo, Lisa A.; Pigula, Frank; Jonas, Richard A.; Newburger, Jane W.

    2009-01-01

    Objective Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing two-ventricle repair in infancy and to determine risk factors associated with such injury. Methods Forty-eight infants enrolled in a trial comparing two different hematocrits during surgical repair of congenital heart disease underwent brain MRI scans and neurodevelopmental testing at one year of age. Results Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional MRI sequences. Subjects who had foci of hemosiderin had a significantly lower Psychomotor Developmental Index at one year of age (79.6 ± 16.5, mean ± SD) compared with subjects who did not have these foci (89.5 ± 15.3; p=0.04). Older age at surgery and diagnostic group were significantly associated with presence of hemosiderin foci. Only one subject had a small stroke (2%) and two had periventricular leukomalacia (4%). Conclusions Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in MRI studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis and not risk factors associated with brain injury in previous studies suggests that the etiology and pathogenesis of this abnormality is different from ischemic brain lesions reported previously. PMID:19619781

  17. Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness.

    PubMed

    Menegakis, Apostolos; De Colle, Chiara; Yaromina, Ala; Hennenlotter, Joerg; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Noell, Susan; Tatagiba, Marcos; Brucker, Sara; Wallwiener, Diethelm; Boeke, Simon; Ricardi, Umberto; Baumann, Michael; Zips, Daniel

    2015-09-01

    To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Mean frequency and relative fluorescence intensity measurement of γ-H2AX foci dose response in PBL exposed to γ-irradiation: An inter- and intra-laboratory comparison and its relevance for radiation triage.

    PubMed

    Venkateswarlu, Raavi; Tamizh, Selvan G; Bhavani, Manivannan; Kumar, Arun; Alok, Amit; Karthik, Kanagaraj; Kalra, Namita; Vijayalakshmi, J; Paul, Solomon F D; Chaudhury, N K; Venkatachalam, Perumal

    2015-12-01

    Measurement of γ-H2AX protein changes in the peripheral blood lymphocytes (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and rapid assay for radiation triage and early marker of dose estimation. The qualitative and quantitative measurements of the protein changes were examined using flow cytometry and microscopy. Whole blood and isolated lymphocytes were exposed in vitro between 0.1 and 5 Gy doses of (60) Co γ-radiation at a dose rate of 1 Gy/min. Radiation induced γ-H2AX foci frequency (n = 3) and relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs postexposure. The observed dose response for γ-H2AX foci frequency at both time points, for whole blood and isolated lymphocytes did not show any significant (P > 0.05) differences. However, when compared with γ-H2AX foci frequency scored manually (microscopy), the semiautomated analysis (captured images) showed a better correlation (r(2) = 0.918) than that obtained with automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the γ-H2AX foci frequency quantified using microscopy showed a dose dependent increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro. Moreover, a better correlation was observed between the γ-H2AX foci frequency obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that the γ-H2AX foci remain more or less unchanged up to 4 hrs and reduces gradually over 48 hrs of postexposure at 37°C. Further, inter and intra-laboratory comparisons showed consistency in the scoring of γ-H2AX foci frequency by manual and semiautomated scoring. The overall results suggest that measurement of γ-H2AX (microscopy and flow cytometry) should be employed within 4 to 6 hrs for a reliable dosimetry either by sharing the work load between the laboratories or investing more manpower; however, triage can be possible even up to 48 hrs of postirradiation. © 2015 International Society for Advancement of Cytometry.

  19. DNA DSB measurements and modelling approaches based on gamma-H2AX foci time evolution

    NASA Astrophysics Data System (ADS)

    Esposito, Giuseppe; Campa, Alessandro; Antonelli, Francesca; Mariotti, Luca; Belli, Mauro; Giardullo, Paola; Simone, Giustina; Antonella Tabocchini, Maria; Ottolenghi, Andrea

    DNA double strand breaks (DSBs) induced by ionising radiation are considered the main dam-age related to the deleterious consequences in the cells. Unrepaired or mis-repaired DSBs can cause mutations or loss of chromosome regions which can eventually lead to cell death or neo-plastic transformation. Quantification of the number and complexity of DSBs induced by low doses of radiation remains a complex problem. About ten years ago Rogakou et al. proposed an immunofluorescent technique able to detect even a single DSB per cell. This approach is based on the serine 139 phosphorylation of many molecules (up to 2000) of histone H2AX (γg-H2AX) following the induction of a DSB in the DNA. DSB can be visualized as foci by immunofluores-cence by using phospho-specific antibodies, so that enumeration of foci can be used to measure DSB induction and processing. It is still not completely clear how γ-H2AX dephosphorylation takes place; however it has been related with DSB repair, in particular with the efficiency of DSB repair. In this work we analyse the H2AX phosphorylation-dephosphorylation kinetics after irradiation of primary human fibroblasts (AG1522 cell line) with radiation of differing quality, that is γ-rays and α-particles (125 keV/µm), with the aim of comparing the time evolution of γ-H2AX foci. Our results show that, after a dose of 0.5 Gy, both γ-rays and α-particles induce the maximum number of γ-H2AX foci within 30 minutes from irradiation, that this number depends on the radiation type and is consistent with the number of track traversal in α-irradiated nuclei, that the dephosphorylation kinetics are very different, being the α-induced foci rate of disappearence slower than that of γ-induced foci. In this work a modellistic approach to estimate the number of DSB induced by γ-rays detectable by using the γ-H2AX assay is presented. The competing processes of appearance and disappearance of visible foci will be modeled taking into account the phosphorylation and dephosphorylation phenomena. The effect of possible overlapping DSB induced at short distance (within 2 Mbp) will be also taken into account. Moreover, for charged particles (in particular for α-particles) the average number of DSB per focus is calculated.

  20. Increased γ-H2A.X Intensity in Response to Chronic Medium-Dose-Rate γ-Ray Irradiation

    PubMed Central

    Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

    2012-01-01

    Background The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. Methodology/Principal Findings We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G1 phase, although no significant difference was observed in G2/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G1 phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G1 phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Conclusions Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation. PMID:23028931

  1. [The pathogenic ecology research on plague in Qinghai plateau].

    PubMed

    Dai, Rui-xia; Wei, Bai-qing; Li, Cun-xiang; Xiong, Hao-ming; Yang, Xiao-yan; Fan, Wei; Qi, Mei-ying; Jin, Juan; Wei, Rong-jie; Feng, Jian-ping; Jin, Xing; Wang, Zu-yun

    2013-12-01

    To study the pathogenic ecology characteristics of plague in Qinghai plateau. Applied molecular biology techniques, conventional technologies and geographic information system (GIS) to study phenotypic traits, plasmid spectrum, genotype, infected host and media spectrum etc.of 952 Yersinia pestis strains in Qinghai plateau plague foci, which were separated from different host and media in different regions during 1954 to 2012. The ecotypes of these strains were Qingzang plateau (91.49%, 871/952),Qilian mountain (6.41%, 61/952) and Microtus fuscus (1.26%, 12/952).83.6% (796/952) of these strains contained all the 4 virulence factors (Fr1, Pesticin1,Virulence antigen, and Pigmentation), 93.26% (367/392) were velogenic strains confirmed by virulence test.725 Yersinia pestis strains were separated from Qinghai plateau plague foci carried 9 kinds of plasmid, among which 713 strains from Marmot himalayan plague foci carried 9 kinds of plasmid, the Mr were 6×10(6), 7×10(6), 23×10(6), 27×10(6), 30×10(6), 45×10(6), 52×10(6), 65×10(6) and 92×10(6) respectively. 12 Yersinia pestis strains were separated from Microtus fuscus plague foci carried only 3 kinds of plasmid, the Mr were 6×10(6), 45×10(6), 65×10(6). Meanwhile, the strains carrying large plasmid (52×10(6), 65×10(6) and 92×10(6)) were only distributed in particular geographical location, which had the category property. The research also confirmed that 841 Yersinia pestis strains from two kinds of plague foci in Qinghai plateau had 11 genomovars. The strains of Marmot himalayan plague foci were given priority to genomovar 5 and 8, amounted to 611 strains, genomovar 8 accounted for 56.00% (471/841), genomovar 5 accounted for 23.07% (194/841). Besides, 3 new genomovars, including new 1(62 strains), new 2(52 strains), new 3(48 strains) were newly founded, and 12 strains of Microtus fuscus plague foci were genomovar 14. The main host and media of Qinghai plateau plague foci directly affected the spatial distribution regularities of plague epidemic and the pathogens characteristics, meanwhile the polymorphism of plague ecological geographic landscape leds to the complexity of Yersinia pestis' genotype.

  2. Separate channels for processing form, texture, and color: evidence from FMRI adaptation and visual object agnosia.

    PubMed

    Cavina-Pratesi, C; Kentridge, R W; Heywood, C A; Milner, A D

    2010-10-01

    Previous neuroimaging research suggests that although object shape is analyzed in the lateral occipital cortex, surface properties of objects, such as color and texture, are dealt with in more medial areas, close to the collateral sulcus (CoS). The present study sought to determine whether there is a single medial region concerned with surface properties in general or whether instead there are multiple foci independently extracting different surface properties. We used stimuli varying in their shape, texture, or color, and tested healthy participants and 2 object-agnosic patients, in both a discrimination task and a functional MR adaptation paradigm. We found a double dissociation between medial and lateral occipitotemporal cortices in processing surface (texture or color) versus geometric (shape) properties, respectively. In Experiment 2, we found that the medial occipitotemporal cortex houses separate foci for color (within anterior CoS and lingual gyrus) and texture (caudally within posterior CoS). In addition, we found that areas selective for shape, texture, and color individually were quite distinct from those that respond to all of these features together (shape and texture and color). These latter areas appear to correspond to those associated with the perception of complex stimuli such as faces and places.

  3. Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier tube

    PubMed Central

    Cha, Jae Won; Yew, Elijah Y. S.; Kim, Daekeun; Subramanian, Jaichandar; Nedivi, Elly; So, Peter T. C.

    2015-01-01

    Multifocal multiphoton microscopy (MMM) improves imaging speed over a point scanning approach by parallelizing the excitation process. Early versions of MMM relied on imaging detectors to record emission signals from multiple foci simultaneously. For many turbid biological specimens, the scattering of emission photons results in blurred images and degrades the signal-to-noise ratio (SNR). We have recently demonstrated that a multianode photomultiplier tube (MAPMT) placed in a descanned configuration can effectively collect scattered emission photons from each focus into their corresponding anodes significantly improving image SNR for highly scattering specimens. Unfortunately, a descanned MMM has a longer detection path resulting in substantial emission photon loss. Optical design constraints in a descanned geometry further results in significant optical aberrations especially for large field-of-view (FOV), high NA objectives. Here, we introduce a non-descanned MMM based on MAPMT that substantially overcomes most of these drawbacks. We show that we improve signal efficiency up to fourfold with limited image SNR degradation due to scattered emission photons. The excitation foci can also be spaced wider to cover the full FOV of the objective with minimal aberrations. The performance of this system is demonstrated by imaging interneuron morphological structures deep in the brains of living mice. PMID:25874160

  4. Multiple foci of spatial attention in multimodal working memory.

    PubMed

    Katus, Tobias; Eimer, Martin

    2016-11-15

    The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition

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

    Matsumoto, Hotaru; Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp; Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto

    2016-07-29

    We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of themore » SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. -- Highlights: •Puromycin exhibits the O-propargyl-puromycin effect. •Puromycin induces SUMO redistribution upon proteasome inhibition. •Ubiquitin and RNF4 accumulate at PML-nuclear bodies with SUMO-2/3. •The ubiquitin family may function in nuclear sequestration of immature proteins.« less

  6. Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas.

    PubMed

    Jacinto, Frances A; Fisher, George H; Espana, Edgar M; Leyngold, Ilya M; Margo, Curtis E

    2016-10-01

    We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas. This article offers a clinicopathological correlation with a review of the relevant literature. An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion. Excisional biopsies revealed that both were primary melanomas arising within in situ disease. Over the span of 25 years, the patient had three separate foci of in situ melanoma, two of which spawned invasive melanoma. Separate melanomas arising from the bulbar conjunctiva and eyelid skin have rarely been reported. Multiple primary melanomas of the skin, however, are not uncommon. Based on studies of persons with multiple cutaneous melanomas, the prognosis is best predicted by the tumor with the greatest depth of invasion. Patients with multiple melanomas should be examined for dysplastic nevi, additional cutaneous melanomas, and screened periodically for future lesions. Ongoing studies enrolling patients with multiple primary melanomas are attempting to generate insights into low-penetrance susceptibility genes.

  7. From Connectivity Models to Region Labels: Identifying Foci of a Neurological Disorder

    PubMed Central

    Venkataraman, Archana; Kubicki, Marek; Golland, Polina

    2014-01-01

    We propose a novel approach to identify the foci of a neurological disorder based on anatomical and functional connectivity information. Specifically, we formulate a generative model that characterizes the network of abnormal functional connectivity emanating from the affected foci. This allows us to aggregate pairwise connectivity changes into a region-based representation of the disease. We employ the variational expectation-maximization algorithm to fit the model and subsequently identify both the afflicted regions and the differences in connectivity induced by the disorder. We demonstrate our method on a population study of schizophrenia. PMID:23864168

  8. FOCIS: A forest classification and inventory system using LANDSAT and digital terrain data

    NASA Technical Reports Server (NTRS)

    Strahler, A. H.; Franklin, J.; Woodcook, C. E.; Logan, T. L.

    1981-01-01

    Accurate, cost-effective stratification of forest vegetation and timber inventory is the primary goal of a Forest Classification and Inventory System (FOCIS). Conventional timber stratification using photointerpretation can be time-consuming, costly, and inconsistent from analyst to analyst. FOCIS was designed to overcome these problems by using machine processing techniques to extract and process tonal, textural, and terrain information from registered LANDSAT multispectral and digital terrain data. Comparison of samples from timber strata identified by conventional procedures showed that both have about the same potential to reduce the variance of timber volume estimates over simple random sampling.

  9. A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

    PubMed

    Eck, Simon; Wörz, Stefan; Müller-Ott, Katharina; Hahn, Matthias; Biesdorf, Andreas; Schotta, Gunnar; Rippe, Karsten; Rohr, Karl

    2016-08-01

    The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Mlh2 Is an Accessory Factor for DNA Mismatch Repair in Saccharomyces cerevisiae

    PubMed Central

    Srivatsan, Anjana; Bowen, Nikki; Gries, Kerstin; Desai, Arshad; Putnam, Christopher D.; Kolodner, Richard D.

    2014-01-01

    In Saccharomyces cerevisiae, the essential mismatch repair (MMR) endonuclease Mlh1-Pms1 forms foci promoted by Msh2-Msh6 or Msh2-Msh3 in response to mispaired bases. Here we analyzed the Mlh1-Mlh2 complex, whose role in MMR has been unclear. Mlh1-Mlh2 formed foci that often colocalized with and had a longer lifetime than Mlh1-Pms1 foci. Mlh1-Mlh2 foci were similar to Mlh1-Pms1 foci: they required mispair recognition by Msh2-Msh6, increased in response to increased mispairs or downstream defects in MMR, and formed after induction of DNA damage by phleomycin but not double-stranded breaks by I-SceI. Mlh1-Mlh2 could be recruited to mispair-containing DNA in vitro by either Msh2-Msh6 or Msh2-Msh3. Deletion of MLH2 caused a synergistic increase in mutation rate in combination with deletion of MSH6 or reduced expression of Pms1. Phylogenetic analysis demonstrated that the S. cerevisiae Mlh2 protein and the mammalian PMS1 protein are homologs. These results support a hypothesis that Mlh1-Mlh2 is a non-essential accessory factor that acts to enhance the activity of Mlh1-Pms1. PMID:24811092

  11. Combined process automation for large-scale EEG analysis.

    PubMed

    Sfondouris, John L; Quebedeaux, Tabitha M; Holdgraf, Chris; Musto, Alberto E

    2012-01-01

    Epileptogenesis is a dynamic process producing increased seizure susceptibility. Electroencephalography (EEG) data provides information critical in understanding the evolution of epileptiform changes throughout epileptic foci. We designed an algorithm to facilitate efficient large-scale EEG analysis via linked automation of multiple data processing steps. Using EEG recordings obtained from electrical stimulation studies, the following steps of EEG analysis were automated: (1) alignment and isolation of pre- and post-stimulation intervals, (2) generation of user-defined band frequency waveforms, (3) spike-sorting, (4) quantification of spike and burst data and (5) power spectral density analysis. This algorithm allows for quicker, more efficient EEG analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Opposed hemispheric specializations for human hypersexuality and orgasm?

    PubMed

    Suffren, Sabrina; Braun, Claude M J; Guimond, Anik; Devinsky, Orrin

    2011-05-01

    With a multiple case report analysis we demonstrate that hypersexuality more often results from right hemisphere (RH) (n=26) than left hemisphere (LH) (n=7) lesions, possibly because of LH release after the RH lesion, and that ictal orgasm more often occurs in patients with right-sided (n=23) than left-sided (n=8) seizure foci, with the symptom probably resulting from RH activation. The LH may be specialized for increasing sexual tension, whereas the RH may be specialized for release of this tension (orgasm), the former being catabolic and the latter anabolic. Several other interpretations of the findings are also discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Lactococcus lactis subsp. lactis infection in Bester sturgeon, a cultured hybrid of Huso huso × Acipenser ruthenus, in Taiwan.

    PubMed

    Chen, Ming-Hui; Hung, Shao-Wen; Shyu, Ching-Lin; Lin, Cheng-Chung; Liu, Pan-Chen; Chang, Chen-Hsuan; Shia, Wei-Yau; Cheng, Ching-Fu; Lin, Shiun-Long; Tu, Ching-Yu; Lin, Yu-Hsing; Wang, Way-Shyan

    2012-10-01

    Approximately 5300 hybrid sturgeons with an average body weight of 600-800 g were farmed in 3 round tankers measuring 3m in diameter each containing 28,000 L of aerated groundwater. According to the owner's description, the diseased fish had anorexia, pale body color, and reddish spots on the abdomen. The morbidity and lethality rates in this outbreak were about 70% (3706/5300) and 100% (3706/3706), respectively. The clinical examination revealed enteritis, enlarged abdomen, and rapid respiration rate. The gross findings revealed a volume of about 4 mL of ascites. The histopathological examination showed multiple massive, hemorrhagic or coagulative necrotic foci in the liver and spleen. Furthermore, there was diffuse infiltration of glycogen in hepatic cells, and a few polymorphonuclear and mononuclear leucocytes were observed surrounding the spleen. Some bacterial clumps were noted around the necrotic foci. We also observed that there was moderate to severe, acute, multifocal, coagulative necrosis in the renal parenchyma, with some necrotic foci present beneath the margin of the kidney. Additionally, multifocal, coagulative necrosis was found in the pancreas. Results of microbiologic examinations, including biochemical characteristics, PCR amplification of 16S rRNA gene, sequencing and comparison, and phylogenetic analysis, revealed the pathogen of this infection was Lactococcus lactis subsp. lactis, and based on the results of an antimicrobial agent sensitivity test the bacterium was only sensitive to ampicillin and florfenicol. Additionally, results of in vivo experimental infections in hybrid tilapia showed that 1×10(8) and 1×10(9) CFU/mL of our isolate caused death in all fish and LD(50) values ranged from 10(2) to 10(5) CFU/mL. To the best of the authors' knowledge, this is the first reported case of Lactococcus lactis subsp. lactis infection in hybrid sturgeon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Factors predictive of immediate breast reconstruction following mastectomy for invasive breast cancer in Australia.

    PubMed

    Roder, D; Zorbas, H; Kollias, J; Pyke, C; Walters, D; Campbell, I; Taylor, C; Webster, F

    2013-12-01

    To investigate person, cancer and treatment determinants of immediate breast reconstruction (IBR) in Australia. Bi-variable and multi-variable analyses of the Quality Audit database. Of 12,707 invasive cancers treated by mastectomy circa 1998-2010, 8% had IBR. This proportion increased over time and reduced from 29% in women below 30 years to approximately 1% in those aged 70 years or more. Multiple regression indicated that other IBR predictors included: high socio-economic status; private health insurance; being asymptomatic; a metropolitan rather than inner regional treatment centre; higher surgeon case load; small tumour size; negative nodal status, positive progesterone receptor status; more cancer foci; multiple affected breast quadrants; synchronous bilateral cancer; not having neo-adjuvant chemotherapy, adjuvant radiotherapy or adjuvant hormone therapy; and receiving ovarian ablation. Variations in access to specialty services and other possible causes of variations in IBR rates need further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Unilateral giant cell lesion of the jaw in Noonan syndrome.

    PubMed

    Eyselbergs, M; Vanhoenacker, F; Hintjens, J; Dom, M; Devriendt, K; Van Dijck, H

    2014-01-01

    Noonan syndrome (NS) is an etiologically heterogeneous disorder caused by mutations in the RAS-MAPK signaling pathway. Noonan-Like/Multiple Giant Cell Lesion (NL/MGCL) syndrome is initially described as the occurrence of multiple gnathic giant cell lesions in patients with phenotypic features of NS. Nowadays, NS/MGCL syndrome is considered a variant of the NS spectrum rather than a distinct entity. We report the case of a 14-year-old female patient carrying a SOS1 mutation with a unilateral giant cell lesion of the right mandible. Cross-sectional imaging such as CT and MRI are not specific for the diagnosis of oral giant cell lesions. Nonetheless, intralesional scattered foci of low SI on T2-WI, corresponding to hemosiderin deposits due to hemorrhage, can help the radiologist in narrowing down the differential diagnosis of gnathic lesions in patients with NS.

  16. Sarcocystis neurona encephalitis in a dog.

    PubMed

    Cooley, A J; Barr, B; Rejmanek, D

    2007-11-01

    A 1.5-year-old male Feist dog was presented to a veterinarian for reluctance to stand on the hind legs. Treatment included dexamethasone and resulted in a favorable initial response, but posterior paresis returned and progressed to recumbency, hyperesthesia, and attempts to bite the owner. The dog was euthanized. The brain was negative for rabies by fluorescent antibody analysis. Multiple foci of encephalitis were found in the cerebrum and particularly in the cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were identified at sites of intense inflammation and malacia. Additionally, multiple schizonts were identified in areas without inflammation. Immunohistochemistry using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii or Neospora caninum was found. Polymerase chain reaction confirmed that the protozoa were S. neurona. Additional aberrant hosts for S. neurona other than horses have been identified, but S. neurona encephalitis has not been documented previously in the dog.

  17. Energy Efficiency of a New Trifocal Intraocular Lens

    NASA Astrophysics Data System (ADS)

    Vega, F.; Alba-Bueno, F.; Millán, M. S.

    2014-01-01

    The light distribution among the far, intermediate and near foci of a new trifocal intraocular lens (IOL) is experimentally determined, as a function of the pupil size, from image analysis. The concept of focus energy efficiency is introduced because, in addition to the theoretical diffraction efficiency of the focus, it accounts for other factors that are naturally presented in the human eye such as the level of spherical aberration (SA) upon the IOL, light scattering at the diffractive steps or the depth of focus. The trifocal IOL is tested in-vitro in two eye models: the aberration-free ISO model, and a so called modified-ISO one that uses an artificial cornea with positive spherical SA in instead. The SA upon the IOL is measured with a Hartmann-Shack sensor and compared to the values of theoretical eye models. The results show, for large pupils, a notorious reduction of the energy efficiency of the far and near foci of the trifocal IOL due to two facts: the level of SA upon the IOL is larger than the value the lens is able to compensate for and there is significant light scattering at the diffractive steps. On the other hand, the energy efficiency of the intermediate focus for small pupils is enhanced by the contribution of the extended depth of focus of the near and far foci. Thus, while IOLs manufacturers tend to provide just the theoretical diffraction efficiency of the foci to show which would be the performance of the lens in terms of light distribution among the foci, our results put into evidence that this is better described by using the energy efficiency of the foci.

  18. Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks.

    PubMed

    Rybak, Paulina; Hoang, Agnieszka; Bujnowicz, Lukasz; Bernas, Tytus; Berniak, Krzysztof; Zarębski, Mirosław; Darzynkiewicz, Zbigniew; Dobrucki, Jerzy

    2016-08-02

    Phosphorylation of histone H2AX on serine 139 (γH2AX) is an early step in cellular response to a DNA double-strand break (DSB). γH2AX foci are generally regarded as markers of DSBs. A growing body of evidence demonstrates, however, that while induction of DSBs always brings about phosphorylation of histone H2AX, the reverse is not true - the presence of γH2AX foci should not be considered an unequivocal marker of DNA double-strand breaks. We studied DNA damage induced in A549 human lung adenocarcinoma cells by topoisomerase type I and II inhibitors (0.2 μM camptothecin, 10 μM etoposide or 0.2 μM mitoxantrone for 1 h), and using 3D high resolution quantitative confocal microscopy, assessed the number, size and the integrated intensity of immunofluorescence signals of individual γH2AX foci induced by these drugs. Also, investigated was spatial association between γH2AX foci and foci of 53BP1, the protein involved in DSB repair, both in relation to DNA replication sites (factories) as revealed by labeling nascent DNA with EdU. Extensive 3D and correlation data analysis demonstrated that γH2AX foci exhibit a wide range of sizes and levels of H2AX phosphorylation, and correlate differently with 53BP1 and DNA replication. This is the first report showing lack of a link between low level phosphorylation γH2AX sites and double-strand DNA breaks in cells exposed to topoisomerase I or II inhibitors. The data are discussed in terms of mechanisms that may be involved in formation of γH2AX sites of different sizes and intensities.

  19. Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells.

    PubMed

    Banáth, J P; Bañuelos, C A; Klokov, D; MacPhail, S M; Lansdorp, P M; Olive, P L

    2009-05-01

    Pluripotent mouse embryonic stem cells (mES cells) exhibit approximately 100 large gammaH2AX repair foci in the absence of measurable numbers of DNA double-strand breaks. Many of these cells also show excessive numbers of DNA single-strand breaks (>10,000 per cell) when analyzed using the alkaline comet assay. To understand the reasons for these unexpected observations, various methods for detecting DNA strand breaks were applied to wild-type mES cells and to mES cells lacking H2AX, ATM, or DNA-PKcs. H2AX phosphorylation and expression of other repair complexes were measured using flow and image analysis of antibody-stained cells. Results indicate that high numbers of endogenous gammaH2AX foci and single-strand breaks in pluripotent mES cells do not require ATM or DNA-PK kinase activity and appear to be associated with global chromatin decondensation rather than pre-existing DNA damage. This will limit applications of gammaH2AX foci analysis in mES cells to relatively high levels of initial or residual DNA damage. Excessive numbers of single-strand breaks in the alkaline comet assay can be explained by the vulnerability of replicating chromatin in mES cells to osmotic shock. This suggests that caution is needed in interpreting results with the alkaline comet assay when applied to certain cell types or after treatment with agents that make chromatin vulnerable to osmotic changes. Differentiation of mES cells caused a reduction in histone acetylation, gammaH2AX foci intensity, and DNA single-strand breakage, providing a link between chromatin structural organization, excessive gammaH2AX foci, and sensitivity of replicating mES cell chromatin to osmotic shock.

  20. Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

    PubMed

    Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

    2016-05-01

    Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Quantitative high resolution mapping of HvMLH3 foci in barley pachytene nuclei reveals a strong distal bias and weak interference

    PubMed Central

    Phillips, Dylan; Wnetrzak, Joanna; Nibau, Candida; Barakate, Abdellah; Ramsay, Luke; Wright, Frank; Higgins, James D.; Perry, Ruth M.; Jenkins, Glyn

    2013-01-01

    In barley (Hordeum vulgare L.), chiasmata (the physical sites of genetic crossovers) are skewed towards the distal ends of chromosomes, effectively consigning a large proportion of genes to recombination coldspots. This has the effect of limiting potential genetic variability, and of reducing the efficiency of map-based cloning and breeding approaches for this crop. Shifting the sites of recombination to more proximal chromosome regions by forward and reverse genetic means may be profitable in terms of realizing the genetic potential of the species, but is predicated upon a better understanding of the mechanisms governing the sites of these events, and upon the ability to recognize real changes in recombination patterns. The barley MutL Homologue (HvMLH3), a marker for class I interfering crossovers, has been isolated and a specific antibody has been raised. Immunolocalization of HvMLH3 along with the synaptonemal complex transverse filament protein ZYP1, used in conjunction with fluorescence in situ hybridization (FISH) tagging of specific barley chromosomes, has enabled access to the physical recombination landscape of the barley cultivars Morex and Bowman. Consistent distal localization of HvMLH3 foci throughout the genome, and similar patterns of HvMLH3 foci within bivalents 2H and 3H have been observed. A difference in total numbers of HvMLH3 foci between these two cultivars has been quantified, which is interpreted as representing genotypic variation in class I crossover frequency. Discrepancies between the frequencies of HvMLH3 foci and crossover frequencies derived from linkage analysis point to the existence of at least two crossover pathways in barley. It is also shown that interference of HvMLH3 foci is relatively weak compared with other plant species. PMID:23554258

  2. Ultraviolet-induced movement of the human DNA repair protein, xeroderma pigmentosum type G, in the nucleus

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

    Park, M.S.; Knauf, J.A.; Pendergrass, S.H.

    1996-08-06

    Xeroderma pigmentosum type G (XPG) is a human genetic disease exhibiting extreme sensitivity to sunlight. XPG patients are defective XPG endonuclease, which is an enzyme essential for DNA repair of the major kinds of solar ultraviolet (UV)-induced DNA damages. Here we describe a novel dynamics of this protein within the cell nucleus after UV irradiation of human cells. USing confocal microscopy, we have localized the immunofluorescent, antigenic signal of XPG protein to foci throughout the cell nucleus. Our biochemical studies also established that XPG protein forms a tight association with nuclear structure(s). In human skin fibroblast cells, the number ofmore » XPG foci decreased within 2 h after UV irradiation, whereas total nuclear XPG fluorescence intensity remained constant, suggesting redistribution of XPG from a limited number of nuclear foci to the nucleus overall. Within 8 h after UV, most XPG antigenic signal was found as foci. Using {beta}-galactosidase-XPG fusion constructs ({beta}-gal-XPG) transfected into HeLa cells, we have identified a single region of XPG that is evidently responsible both for foci formation and for the UV dynamic response. The fusion protein carrying the C terminus of XPG (amino acids 1146-1185) localized {beta}-gal specific antigenic signal to foci and to the nucleolus regions. After UV irradiation, antigenic {beta}-gal translocated reversibly from the subnuclear structures to the whole nucleus with kinetics very similar to the movements of XPG protein. These findings lead us to propose a model in which distribution of XPG protein may regulate the rate of DNA repair within transcriptionally active and inactive compartments of the cell nucleus. 50 refs., 5 figs., 1 tab.« less

  3. Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors

    PubMed Central

    Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-ping; Young, Lauren F.; Shieh, Jae-Hung; Moore, Malcolm A.; van den Brink, Marcel R.M.; Kusunoki, Yoichiro

    2016-01-01

    Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. PMID:27169377

  4. FANC Pathway Promotes UV-Induced Stalled Replication Forks Recovery by Acting Both Upstream and Downstream Polη and Rev1

    PubMed Central

    Renaud, Emilie; Rosselli, Filippo

    2013-01-01

    To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised DNA polymerases or tolerate the lesions using homologous recombination (HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled replication forks, we analysed the molecular crosstalk between the TLS DNA polymerases Polη and Rev1, the double-strand break repair (DSB)-associated protein MDC1 and the FANC pathway. We describe three novel functional interactions that occur in response to UVC-induced DNA lesions. First, Polη and Rev1, whose optimal expression and/or relocalisation depend on the FANC core complex, act upstream of FANCD2 and are required for the proper relocalisation of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are independently required for optimal BRCA1 relocalisation. While RPA32 phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the basis of the previous observations, we propose that the FANC pathway participates in the rescue of UVC-stalled replication forks in association with TLS by maintaining the integrity of ssDNA regions and by preserving genome stability and preventing the formation of DSBs, the resolution of which would require the intervention of MDC1. PMID:23365640

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

    United States. Bonneville Power Administration, Portland, OR; Oregon Department of Agriculture Noxious Weed Control Program

    During the 1996 season ODA executed the contract between BPA and ODA. Execution of this contract included the following activities: Survey for target noxious weeds, such as Gorse; collection and redistribution of biological control agents, for example, Apion seed weevils for Scotch broom, bioagents for diffuse and spotted knapweed, Gorse spider mite, and gall fly releases for control of Canada thistle and bull thistle; and control of isolated infestations of Gorse on BPA rights-of-way. Training was provided for line crews at the Chemawa, Alevy and North Bend districts. The purpose of the program is to assist BPA in the integratedmore » prevention and control of noxious weed species on BPA transmission line maintenance right-of-ways.« less

  6. Anesthetic effects on fictive locomotion in the rat isolated spinal cord

    PubMed Central

    Jinks, Steven L.; Andrada, Jason; Satter, Omar

    2011-01-01

    General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation. PMID:21817927

  7. Responsibility modulates pain-matrix activation elicited by the expressions of others in pain

    PubMed Central

    Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria

    2015-01-01

    Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured. PMID:25800210

  8. Carcinoma in gastric hyperplastic polyps: A phenotypic study

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

    Zea-Iriarte, W.L.; Sekine, Ichiro; Itsuno, Minoru

    1996-02-01

    One-hundred twelve hyperplastic polyps were analyzed. The aim was to study their malignant transformation. Among them, four hyperplastic polyps harbored adenocarcinoma; two were from our own institution (1.8%). The majority were pedunculated and located in the antrum with an average of 14.5 mm in diameter. The four polyps bore well-differentiated adenocarcinoma. Dysplasia and intestinal metaplasia were detected in two and three polyps, respectively. The cancer and dysplastic foci shared the same type of neutral and acid mucosubstances. p53 oncoprotein was positive in three cancer foci and in the dysplastic areas, and nucleolar organizer region counts were higher in the cancermore » foci. In conclusion, hyperplastic polyps have malignant potential. Such possibility increases in polyps larger than 14.5 mm. In our cases, the carcinoma foci may have arisen from dysplastic areas. Once the neoplastic changes occur, the cancer cells proliferate and behave as other adenocarcinomas of the stomach. 40 refs., 7 figs., 5 tabs.« less

  9. [THE PRESENT STATE OF EPIZOOTOLOGICAL MONITORING OF THE NATURAL FOCI OF INFECTIONS IN THE RUSSIAN FEDERATION].

    PubMed

    Trankvilevsky, D V; Tsarenko, V A; Zhukov, V I

    2016-01-01

    The facilities of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare play a leading role in epizootological monitoring. The specialists (zoologists and entomologists) of Hygiene and Epidemiology Centers do basic work in the subjects of the Russian Federation. The data obtained in the participation of different ministries and departments are used to analyze the results of monitoring. The latter is one of the important steps in the management of the epidemic, process in natural focal infections. In recent years, there has been an unjustified reduction in the volume of studies in the natural foci. This negatively affects the reliability of estimates and predictions of the epidemic activity of the natural foci of infections. Ensuring the national, security of the Russian Federation, epidemiological surveillance, and control of its natural foci requires staffing and appropriate professional training in the zoological and entomological subdivisions of the Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare.

  10. Small Rad51 and Dmc1 Complexes Often Co-occupy Both Ends of a Meiotic DNA Double Strand Break

    PubMed Central

    Brown, M. Scott; Grubb, Jennifer; Zhang, Annie; Rust, Michael J.; Bishop, Douglas K.

    2015-01-01

    The Eukaryotic RecA-like proteins Rad51 and Dmc1 cooperate during meiosis to promote recombination between homologous chromosomes by repairing programmed DNA double strand breaks (DSBs). Previous studies showed that Rad51 and Dmc1 form partially overlapping co-foci. Here we show these Rad51-Dmc1 co-foci are often arranged in pairs separated by distances of up to 400 nm. Paired co-foci remain prevalent when DSBs are dramatically reduced or when strand exchange or synapsis is blocked. Super-resolution dSTORM microscopy reveals that individual foci observed by conventional light microscopy are often composed of two or more substructures. The data support a model in which the two tracts of ssDNA formed by a single DSB separate from one another by distances of up to 400 nm, with both tracts often bound by one or more short (about 100 nt) Rad51 filaments and also by one or more short Dmc1 filaments. PMID:26719980

  11. Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees

    PubMed Central

    Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

    2016-01-01

    The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected. PMID:27534586

  12. Centralization of Noxious Stimulus-induced Analgesia (NSIA) is Related to Activity at Inhibitory Synapses in the Spinal Cord

    PubMed Central

    Tambeli, Claudia H.; Levine, Jon D.; Gear, Robert W.

    2009-01-01

    The duration of noxious stimulus-induced antinociception (NSIA) has been shown to outlast the pain stimulus that elicited it, however, the mechanism that determines the duration of analgesia is unknown. We evaluated the role of spinal excitatory and inhibitory receptors (NMDA, mGluR-5, mu-opioid, GABA-A, and GABA-B), previously implicated in NSIA initiation, in its maintenance. As in our previous studies, the supraspinal trigeminal jaw-opening reflex (JOR) in the rat was used for nociceptive testing because of its remoteness from the region of drug application, the lumbar spinal cord. NSIA was reversed by antagonists for two inhibitory receptors (GABA-B and mu-opioid) but not by antagonists for either of the two excitatory receptors (NMDA and mGluR-5), indicating that NSIA is maintained by ongoing activity at inhibitory synapses in the spinal cord. Furthermore, spinal administration of the GABA-B agonist baclofen mimicked NSIA in that it could be blocked by prior injection of the mu-opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in nucleus accumbens. CTAP also blocked baclofen antinociception when administered in the spinal cord. We conclude that analgesia induced by noxious stimulation is maintained by activity in spinal inhibitory receptors. PMID:19375225

  13. Absence of food alternatives promotes risk-prone feeding of unpalatable substances in honey bees.

    PubMed

    Desmedt, Lucie; Hotier, Lucie; Giurfa, Martin; Velarde, Rodrigo; de Brito Sanchez, Maria Gabriela

    2016-08-18

    The question of why animals sometimes ingest noxious substances is crucial to understand unknown determinants of feeding behaviour. Research on risk-prone feeding behaviour has largely focused on energy budgets as animals with low energy budgets tend to ingest more aversive substances. A less explored possibility is that risk-prone feeding arises from the absence of alternative feeding options, irrespectively of energy budgets. Here we contrasted these two hypotheses in late-fall and winter honey bees. We determined the toxicity of various feeding treatments and showed that when bees can choose between sucrose solution and a mixture of this sucrose solution and a noxious/unpalatable substance, they prefer the pure sucrose solution and reject the mixtures, irrespective of their energy budget. Yet, when bees were presented with a single feeding option and their escape possibilities were reduced, they consumed unexpectedly some of the previously rejected mixtures, independently of their energy budget. These findings are interpreted as a case of feeding helplessness, in which bees behave as if it were utterly helpless to avoid the potentially noxious food and consume it. They suggest that depriving bees of variable natural food sources may have the undesired consequence of increasing their acceptance of food that would be otherwise rejected.

  14. Responses of dorsal spinal cord blood flow to noxious mechanical stimulation of the skin in anesthetized rats.

    PubMed

    Toda, Hiroko; Maruyama, Hitoshi; Budgell, Brian; Kurosawa, Mieko

    2008-08-01

    In urethane-anesthetized, artificially ventilated rats, alterations in dorsal spinal cord blood flow (SCBF) at the L4-6 level were measured with laser Doppler flowmetry in response to noxious mechanical cutaneous stimulation (pinching) of either a forepaw or a hindpaw. The stimulation was delivered ipsilaterally or contralaterally to the site of blood flow measurement. Pinching of the forepaw or the hindpaw on either side increased mean arterial pressure (MAP) to the same degree. However, the SCBF response to pinching of the ipsilateral hindpaw was significantly greater than that to other stimulations. These responses were not influenced by denervation of the baroreceptors. The responses of SCBF to pinching of the ipsilateral hindpaw persisted both after treatment with phenoxybenzamine and after spinalization at the C1-2 level, whereas the responses to pinching at other sites disappeared. The responses of MAP to stimulation at all four sites became negligible after treatment with phenoxybenzamine and after spinalization at the C1-2 level. These results indicate that noxious mechanical stimulation of the skin produces increases in SCBF via two mechanisms: one is via an elevation of systemic arterial pressure; the other is via a localized spinal mechanism evoked by ipsilateral, segmental inputs.

  15. The noxious effects of electroimmobilization in adult Holstein cows: a pilot study.

    PubMed Central

    Pascoe, P J; McDonell, W N

    1986-01-01

    Ten adult Holstein cows were used in an experiment to determine whether the induction of electroimmobilization was a noxious event. The cows were halter trained and accustomed to being led into a set of stocks. The time taken for the cattle to walk the last ten metres into the stocks was recorded. The heart rate of the cow was recorded for a three minute period prior to a ten second exposure to a high pitched sound (the conditioning stimulus). Measurements were collected for three repetitions and then the cows were assigned to two groups of five. One group was immobilized for 30 seconds using a commercial electroimmobilizer, the other group was not treated. This procedure was repeated ten times over a period of eight days. The cows were then exposed to the conditioning stimulus and their response observed. The treated group took significantly (P less than 0.05) longer to get into the stocks and the regression slopes for heart rate were significantly different from the control group. The treated cows responded to the conditioning stimulus at five and nine months after the end of the conditioning period. Adult Holstein cows regarded electroimmobilization as a noxious event and were very strongly conditioned to this stimulus. PMID:3756681

  16. Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy

    PubMed Central

    Eshleman, Nichole; Liu, Guangbo; McGrath, Kaitlyn; Parker, Roy; Buchan, J. Ross

    2016-01-01

    The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3′ end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci (“TT foci”) are not stress granules but instead are a mRNP granule containing poly(A)+ mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3′ end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus. PMID:27251550

  17. Evaluation of research topic evolution in psychiatry using co-word analysis

    PubMed Central

    Wu, Ying; Jin, Xing; Xue, Yunzhen

    2017-01-01

    Abstract With the rapid increase in the incidence of mental disorders and mental issues, psychiatry has become one of the fastest growing clinical medical disciplines. Development priorities and research foci in this field have evolved over different periods. All the articles in 10 psychiatric journals with the highest impact factors were selected from the Science Citation Index (SCI) in Web of Science from 2001 to 2015. The information visualization software Sci2 was used to conduct co-word and clustering analyses on these articles. The articles were divided into 3 periods: 2001 to 2005, 2006 to 2010, and 2011 to 2015. Each bibliographic record contained a title, author names, abstract, keywords, references, and other information. During the 3 periods between 2001 and 2015, child and adolescent psychiatry, major depression, schizophrenia, and prefrontal cortex were constant research foci. The brain and meta-analysis gradually became new research foci, although research on symptoms slowly decreased. Molecular genetics was also an area of interest. Using scientometrics technology to visualize research foci can provide us with new ideas and research methods. Co-word analysis for the preliminary exploration of research foci and developmental trends in psychiatry is helpful in finding developmental rules, choices of topics, and innovative research. Our study had some limitations. In the future, we should expand our research scope and use a variety of research methods to enrich our results. PMID:28640150

  18. Evaluation of research topic evolution in psychiatry using co-word analysis.

    PubMed

    Wu, Ying; Jin, Xing; Xue, Yunzhen

    2017-06-01

    With the rapid increase in the incidence of mental disorders and mental issues, psychiatry has become one of the fastest growing clinical medical disciplines. Development priorities and research foci in this field have evolved over different periods.All the articles in 10 psychiatric journals with the highest impact factors were selected from the Science Citation Index (SCI) in Web of Science from 2001 to 2015. The information visualization software Sci was used to conduct co-word and clustering analyses on these articles. The articles were divided into 3 periods: 2001 to 2005, 2006 to 2010, and 2011 to 2015. Each bibliographic record contained a title, author names, abstract, keywords, references, and other information.During the 3 periods between 2001 and 2015, child and adolescent psychiatry, major depression, schizophrenia, and prefrontal cortex were constant research foci. The brain and meta-analysis gradually became new research foci, although research on symptoms slowly decreased. Molecular genetics was also an area of interest.Using scientometrics technology to visualize research foci can provide us with new ideas and research methods. Co-word analysis for the preliminary exploration of research foci and developmental trends in psychiatry is helpful in finding developmental rules, choices of topics, and innovative research. Our study had some limitations. In the future, we should expand our research scope and use a variety of research methods to enrich our results.

  19. Piscine orthoreovirus (PRV) in red and melanised foci in white muscle of Atlantic salmon (Salmo salar).

    PubMed

    Bjørgen, Håvard; Wessel, Øystein; Fjelldal, Per Gunnar; Hansen, Tom; Sveier, Harald; Sæbø, Håkon Rydland; Enger, Katrine Bones; Monsen, Eirik; Kvellestad, Agnar; Rimstad, Espen; Koppang, Erling Olaf

    2015-09-08

    Melanised focal changes (black spots) are common findings in the white skeletal muscle of seawater-farmed Atlantic salmon (Salmo salar). Fillets with melanised focal changes are considered as lower quality and cause large economic losses. It has been suggested that red focal changes (red spots) precede the melanised focal changes. In the present work, we examined different populations of captive and wild salmon for the occurrence of both types of changes, which were investigated for the presence of different viruses by immunohistochemistry and RT-qPCR. The occurrence of red or melanised foci varied significantly between the populations, from none in wild fish control group, low prevalence of small foci in fish kept in in-house tanks, to high prevalence of large foci in farm-raised salmon. Large amounts of Piscine orthoreovirus (PRV) antigen were detected in all foci. No other viruses were detected. Red focal changes contained significantly higher levels of PRV RNA than apparently non-affected areas in white muscle of the same individuals. Some changes displayed a transient form between a red and melanised pathotype, indicating a progression from an acute to a chronic manifestation. We conclude that PRV is associated with the focal pathological changes in the white muscle of farmed Atlantic salmon and is a premise for the development of focal melanised changes.

  20. 7 CFR 360.200 - Designation of noxious weeds.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... mantegazzianum Sommier & Levier (giant hogweed) Homeria spp. Imperata brasiliensis Trinius (Brazilian satintail) Imperata cylindrica (Linnaeus) Raeuschel (cogongrass) Ischaemum rugosum Salisbury (murainograss) Leptochloa...

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