Kinetics of propagation of bystander effects in human cells cultures exposed to low fluences of high LET radiations

International audienceWe and others have previously shown, in confluent cell cultures exposed to low fluences of a particles, that the proportion of cells that upregulate stress-inducible proteins is much higher that the number of cells irradiated. This phenomenon, called bystander effect, is now well accepted and is thought to impact the health risks of exposure to ionizing radiation. Here, we investigate the kinetics of propagation of signaling events that lead to induction of DNA damage in bystander cells in confluent normal human AG1522 fibroblasts exposed to a mean dose of 0.2 cGy from 3.2 MeV a particles (LET ; 124 keV/lm) or 1 GeV/n iron ions (LET ; 151 keV/lm). We evaluated the formation of 53BP1 foci (p53 binding protein 1), which localizes at sites of DNA double strand breaks, as a function of time after irradiation. The fraction of cells whose nuclei were traversed by an irradiating particle was derived from Poisson statistics and estimates of cell geometry, particle fluence and energy loss. At a mean dose of 0.2 cGy, only 1.4% and 1.2% of the cells are traversed through the nucleus by a particle or iron ion tracks, respectively. The number of 53BP1 foci in control cells was ; 0.61 foci per cell. In a particle-irradiated cell cultures, the mean number of foci per cell was 0.73 (p,0.001) at 15 min; it reached 0.90 by 3h (p,0.001) after irradiation, following which a decrease was observed. The same trend was detected when the fraction of cells with foci was considered: it reached 61% at 3h which is higher than the expected 47.4% of the cells (46% in control + 1.4% traversed). The increase in foci formation over the expected value was eliminated when the cells were incubated with a specific inhibitor of ATM (Ataxia Telangiectasia Mutated protein). Analyses of bystander effects in iron ion-irradiated cell cultures and the effect of partial oxygen tension on the kinetic of 53BP1 foci formation in low fluences alpha particle-irradiated cell populations are in progress

Electromagnetic Radiation Hardness of Diamond Detectors

The behavior of artificially grown CVD diamond films under intense electromagnetic radiation has been studied. The properties of irradiated diamond samples have been investigated using the method of thermally stimulated current and by studying their charge collection properties. Diamonds have been found to remain unaffected after doses of 6.8 MGy of 10 keV photons and 10 MGy of MeV-range photons. This observation makes diamond an attractive detector material for a calorimeter in the very forward region of the proposed TESLA detector.Comment: 19 pages, 9 figure

Non-targeted Stressful Effects in Normal Human Fibroblast Cultures Exposed to Low Fluences of High Charge, High-Energy (HZE) Particles: Kinetics of Biologic Responses and Significance of Secondary Radiations.

International audienceThe induction of nontargeted stressful effects in cell populations exposed to low fluences of high-charge (Z) and high-energy (E) particles is relevant to estimates of the health risks of space radiation. We investigated the up-regulation of stress markers in confluent normal human fibroblast cultures exposed to 1,000 MeV/u iron ions [linear energy transfer (LET) ∼151 keV/μm] or 600 MeV/u silicon ions (LET ∼50 keV/μm) at mean absorbed doses as low as 0.2 cGy, wherein 1-3% of the cells were targeted through the nucleus by a primary particle. Within 24 h postirradiation, significant increases in the levels of phospho-TP53 (serine 15), p21(Waf1) (CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation were detected, which suggested participation in the stress response of cells not targeted by primary particles. This was supported by in situ studies that indicated greater increases in 53BP1 foci formation, a marker of DNA damage. than expected from the number of primary particle traversals. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure of the cell cultures to 0.2 cGy of 3.7 MeV α particles (LET ∼109 keV/μm) that targets ∼1.6% of nuclei, but not after 0.2 cGy from 290 MeV/u carbon ions (LET ∼13 keV/μm) by which, on average, ∼13% of the nuclei were hit, which highlights the importance of radiation quality in the induced effect. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cell cultures exposed to HZE particles comprise <1% of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10-20 μm. Thus, the latter are unlikely to significantly contribute to stressful effects in cells not targeted by primary HZE particles

Dewey and the democratic curriculum

This paper uses Dewey’s seminal Democracy and Education (1916) as a key text to investigate the concept of the democratic curriculum. I argue that a democratic curriculum is one where a series of educational innovations or procedures are followed. These are: a removal of the exisiting division between ‘academic’ and ‘vocational’ education; pedagogy in the form of discussion and dialogue; negotiation of curriculum aims and objectives with students and other local stakeholders. The focus of attention will be on the English school curriculum (both primary and secondary), especially concerning the National Curriculum, and the debate over ‘standards’ and testing . A tentative link between the democratic curriculum and increased student motivation and participation is made

Automatic detection and tracking of filaments for a solar feature database

A new method for the automatic detection and tracking of solar filaments is presented. The method addresses the problems facing existing catalogs, such as the one developed recently in the frame of the European Grid of Solar Observations (EGSO) project. In particular, it takes into account the structural and temporal evolution of filaments, differences in intensity as seen from one observation to the next, and the possibility of sudden disappearance followed by reappearance. In this study, the problem of tracking is solved by plotting all detected filaments during each solar rotation on a Carrington map and then by applying region growing techniques on those plots. Using this approach, the &quot;fixed&quot; positions of the envelopes in the Carrington system can be deduced. This is followed by a backward tracking of each filament by considering one full solar rotation. The resulting shifted Carrington map then enables one to follow any filament from one rotation to the next. Such maps should prove valuable for studies of the role of filaments in solar activity, notably coronal mass ejections (CMEs)

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

HIDEA syndrome: A new case report highlighting similarities with ROHHAD syndrome.

peer reviewedContext: ROHHAD syndrome presents a significant resemblance to HIDEA syndrome. The latter is caused by biallelic loss-of-function variants in the P4HTM gene and encompasses hypotonia, intellectual disabilities, eye abnormalities, hypoventilation, and dysautonomia. We report the first patient identified with HIDEA syndrome from our ROHHAD cohort. Clinical case: Our patient was a 21-month-old girl who had a history of severe respiratory infections requiring intensive care, hypotonia, abnormal eye movements, and rapid weight gain. Polysomnography identified severe central hypoventilation. During her follow-up, a significant psychomotor delay and the absence of language were gradually observed. The prolactin levels were initially increased. Hypothermia was reported at 4 years. Exome sequencing identified a new homozygous truncating P4HTM variant. Discussion: Our patient met the diagnosis criteria for ROHHAD, which included rapid weight gain, central hypoventilation appearing after 1.5 years of age, hyperprolactinemia suggesting hypothalamic dysfunction, and autonomic dysfunction manifesting as strabismus and hypothermia. However, she also presented with severe neurodevelopmental delay, which is not a classic feature of ROHHAD syndrome. HIDEA syndrome presents similarities with ROHHAD, including hypoventilation, obesity, and dysautonomia. To date, only 14% of endocrinological disturbances have been reported in HIDEA patients. Better delineation of both syndromes is required to investigate the eventual involvement of P4HTM, a regulator of calcium dynamics and gliotransmission, in ROHHAD patients. Conclusion: In the case of clinical evidence of ROHHAD in a child with abnormal neurological development or eye abnormalities, we suggest that the P4HTM gene be systematically interrogated in addition to the analysis of the PHOX2B gene. A better delineation of the natural history of HIDEA is required to allow further comparisons between features of HIDEA and ROHHAD. The clinical similarities could potentially orient some molecular hypotheses in the field of ROHHAD research

“Excellence R Us”: university research and the fetishisation of excellence

The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship

Dysfunctional play and dopamine physiology in the Fischer 344 rat

Juvenile Fischer 344 rats are known to be less playful than other inbred strains, although the neurobiological substrate(s) responsible for this phenotype is uncertain. In the present study, Fischer 344 rats were compared to the commonly used outbred Sprague-Dawley strain on several behavioral and physiological parameters in order to ascertain whether the lack of play may be related to compromised activity of brain dopamine (DA) systems. As expected, Fischer 344 rats were far less playful than Sprague-Dawley rats, with Fischer 344 rats less likely to initiate playful contacts with a playful partner and less likely to respond playfully to these contacts. We also found that Fischer 344 rats showed less of a startle response and greater pre-pulse inhibition (PPI), especially at higher prepulse intensities. The increase in PPI seen in the Fischer 344 rat could be due to reduced DA modulation of sensorimotor gating and neurochemical measures were consistent with Fischer 344 rats releasing less DA than Sprague-Dawley rats. Fast scan cyclic voltammetry (FSCV) revealed Fischer 344 rats had less evoked DA release in dorsal and ventral striatal brain slices and high-performance liquid chromatography revealed Fischer 344 rats to have less DA turnover in the striatum and prefrontal cortex. We also found DA-dependent forms of cortical plasticity were deficient in the striatum and prefrontal cortex of the Fischer 344 rat. Taken together, these data indicate that deficits in play and enhanced PPI of Fischer 344 rats may be due to reduced DA modulation of corticostriatal and mesolimbic/mesocortical circuits critical to the execution of these behaviors