Age and heat stress as determinants of telomere length in a long-lived fish, the Siberian Sturgeon

Telomeres shorten at each cell division due to the end-replication problem but also in response to oxidative stress. Consequently, telomeres shorten with age in many endotherms, and this shortening is accelerated under stressful environmental conditions. Data in ectotherm vertebrates remain scarce so far, so our goal was to review existing data for fish and to test the influence of age and stress on telomere length in a very long-lived fish, the Siberian sturgeon (Acipenser baerii). Our review of the literature revealed age-related telomere shortening in approximately half of the published studies. In the Siberian sturgeon, we found a significant telomere shortening with age, both at the intraindividual level using red blood cells (−12.5% in 16 mo) and at the interindividual level using cross-sectional samples of fin over an age range of 8 yr. We also found that heat stress (30°C) significantly reduced telomere length by 15.0% after only 1 mo of exposure. Our results highlight that both age and stressful environmental conditions might be important determinants of telomere length in fish

Increased Proton Energies - Above the ~ 60 MeV Empirical Barrier, from High-Contrast High-Intensity Short-Pulse Laser-Interactions with Micro-Cone Targets

Ultra-high intensity lasers enable the investigation of extreme states of matter and the study of high energy density physics in the laboratory, as well as the creation of various intense radiation sources, i.e. electrons, X-rays, and ions. Of particular interest to this dissertation is the production of ion beams from solid targets. These ion beams are directly linked to the hot-electron production and transport inside the solid target (as simple as a metal or CH foil), which requires that electron heating and transport must be well understood in order to increase ion energies and laser-ion conversion efficiencies. Maximizing the energy and/or the conversion efficiency of these ion beams is of considerable interest for many applications, in particular radiation oncology, and inertial confinement fusion with fast ignition. Several approaches have been proposed to maximize the energy and/or the conversion efficiency of the ion beams: instead of using regular size flat-foil targets (i.e. ~ 10 µm thickness, ~ 2x2 mm^2 lateral dimensions), one can use ultrathin targets (thickness of the order of the µm or 100s of nm), very small targets, a.k.a. reduced-mass targets (RMTs) (i.e. lateral dimensions of ~ 100x100 µm^2), or structured targets (e.g. conical-shape targets). These more elaborate targets can increase the hot-electron temperature and/or the hot-electron density. In experiments performed in 2006 on the Trident laser at ~ 20 J, reported in [1], we found that microstructured flat-top cone (FTC) targets, made from Au, yielded an increase in proton energy from 19 MeV to > 30 MeV, and in laser-proton conversion efficiencies from 0.5 % to 2.5 %, as compared to flat-foil targets. These results were postulated to stem from improved laser guiding toward the cone tip, which would lead to higher laser intensities, increased laser absorption and hotter electrons. Improved electron production and transport were also hypothesized to lead to an increase in the hot-electron density and hot-electron temperature at the flat-top. Also postulated was the fact that a longer electron confinement time at the flat-top could lead to RMT-like effects such as resistive/confining edge fields and enhanced target (or flat-top) charge up. We also observed experimentally that, when the laser was misaligned and could not reach the cone tip, or from simulations that, when it was absorbed farther from the flat-top due to an excess in preplasma, the proton acceleration was neither as efficient nor as energetic.After these very promising 2006 results, we endeavored to determine whether this enhancement in proton energy and conversion efficiency would scale for higher laser energies. I participated in the design and the execution of the subsequent experiment, which was performed in 2008, after the Trident laser energy had been upgraded from ~ 20 J to ~ 80 J. This time, surprisingly, we found that the proton energies were in fact lower when FTC targets were used, as opposed to flat-foil targets [2]. To diagnose the laser absorption zone inside the FTC, Cu targets were used (instead of Au) for the purpose of Cu Ka 2-D imaging. I had taken part in an experiment on the LULI laser system earlier in 2008 to learn about Cu Ka imaging techniques; in this experiment, it was observed that, when a portion of the hot-electron population deposits its energy in the laser absorption zone, the emission of Cu Ka X-rays is a direct indication of where the electrons are created, and thus of how much preplasma is filling the cone neck [3]; preplasma is plasma from wall blow-off due to the low level of laser light entering the cone before the main high-intensity pulse, called laser "prepulse". Combining and correlating Cu Ka 2-D imaging with proton acceleration was one of my main goals for this dissertation. At an intrinsic 10^-8 laser contrast, unlike in the 20 J (and ~ 10^19 W/cm^2) case, at 80 J (and ~ 2x10^20 W/cm^2), after the Trident energy enhancement, as well as the addition of a deformable mirror resulting in a spot size decrease from ~ 14 µm down to ~ 7 µm FWHM (with 47 % of the energy in the spot), the amount of plasma prefill (preplasma) prevented the majority of the laser from being efficiently absorbed closer to the cone flat-top or tip [3,4]. The hot-electron population was thus generated away from the flat-top, as indicated by the Cu Ka emission from the cone walls [2], which negatively impacted the proton acceleration, especially in the case of thin FTC necks [1], as the electrons were also not efficiently transported to the flat-top to generate the sheath necessary for ion production. I was also responsible for the electron spectrometer diagnostic; electron spectroscopy confirmed that the temperature of the escaping electrons correlates in a linear fashion with proton energy. Because of the preplasma issues encountered in 2008 due to an insufficient laser contrast (10^-8), I proposed and was the principal investigator of the most recent experiment (2009), which was performed on Trident at ~ 80 J using an enhanced contrast, i.e. this time > 10^-10. In this case, the proton energies were enhanced to 67.5 MeV [5] from 50 MeV when using FTC Cu targets as opposed to flat-foil targets. These results set a new record in laser-accelerated protons. The previous petawatt laser record was 58 MeV with ~ 400 J [6]. Electron spectroscopy in the enhanced contrast case shows an even better correlation with proton energy, due to a cleaner interaction caused by a lower preplasma level. Besides diagnosing the laser alignment or misalignment, I show in this dissertation via Cu Ka imaging, that not only is it crucial to obtain laser absorption at the tip (note that tip heating is dependent on laser contrast and laser intensity [3]), but it is even more important to find the optimum balance [5] between the amount of cone wall emission (CWE) versus top emission (TE) of Cu Ka X-rays. Interestingly, at enhanced contrast, the best results for proton acceleration are obtained when the target-laser interaction is asymmetric: i.e. when the laser interacts with the cone-tip and one sidewall more so than the opposing side. These experimental results directly led to simulations of these asymmetric interactions using a particle-in-cell (PIC) code capable of simulating ultra-intense laser-matter interactions. These simulations results significantly broadened our understanding of this interaction, and explain why the best performing target has a very large neck (i.e. 160 µm), implying that laser light guiding resulting from the cone geometry is not essential, but rather that the grazing of the laser light on as much cone wall surface area as possible (increasing the area where the laser can interact with the wall with a slight angle) is the reason for the observed proton energy enhancement. The knowledge obtained from these series of experiments, supported by the numerical simulations, will help us understand the fundamental laser-cone interaction, and develop new, more efficient targets, hopefully yielding even higher proton energy. __________________________________________________[1] K. A. Flippo, E. d'Humières, S. A. Gaillard, J. Rassuchine, D. C. Gautier, M. Schollmeier, F. Nürnberg, J. L. Kline, J. Adams, B. Albright, M. Bakeman, K. Harres, R. P. Johnson, G. Korgan, S. Letzring, S. Malekos, N. Renard-Le Galloudec, Y. Sentoku, T. Shimada, M. Roth, T. E. Cowan, J. C. Fernández, and B. M. Hegelich, Increased Efficiency of Short-Pulse Laser Generated Proton Beams from Novel Flat-Top Cone Targets, Physics of Plasmas (Invited) 15, 5 (2008).[2] S. A. Gaillard, K. A. Flippo, M. E. Lowenstern, J. E. Mucino, J. M. Rassuchine, D. C. Gautier, J. Workman, and T. E. Cowan, Proton acceleration from ultra high-intensity short-pulse laser-matter interactions with Cu micro-cone targets at the intrinsic ~10-8 contrast, submitted to Journal of Physics Conference Series (JPCS) (2009).[3] J. Rassuchine, E. d'Humières, S. D. Baton, P. Guillou, M. Koenig, M. Chahid, F. Pérez, J. Fuchs, P. Audebert, R. Kodama, M. Nakatsutsumi, N. Ozaki, D. Batani, A. Morace, R. Redaelli, L. Grémillet, C. Rousseaux, F. Dorchies, C. Fourment, J. J. Santos, J. Adams, G. Korgan, S. Malekos, S. B. Hansen, R. Shepherd, K. Flippo, S. Gaillard, Y. Sentoku, and T. E. Cowan, Enhanced hot electron localization and heating in high-contrast ultra-intense laser irradiation of sharp micro-cone targets, Physical Review E 79, 0364408 (2009).[4] S. D. Baton, M. Koenig, J. Fuchs, A. Benuzzi-Mounaix, P. Guillou, B. Loupias, T. Vinci, L. Grémillet, C. Rousseaux, M. Drouin, E. Lefebvre, F. Dorchies, C. Fourment, J. J. Santos, D. Batani, A. Morace, R. Redaelli, M. Nakatsutsumi, R. Kodama, A. Nishida, N. Ozaki, T. Norimatsu, Y. Aglitskiy, S. Atzeni, and A. Schiavi, Inhibition of fast electron energy deposition due to preplasma filling of cone-attached targets, Physics of Plasmas 15, 042706 (2008).[5] S. A. Gaillard, T. Kluge, K. A. Flippo, B. Gall, T. Lockard, M. Schollmeier, M. Geissel, D. T. Offermann, J. M. Rassuchine, D. C. Gautier, E. d'Humières, M. Bussmann, Y. Sentoku, and T. E. Cowan, Increased proton energies up to 67.5 MeV from high-contrast high-intensity short-pulse laser-interactions with micro-cone targets, in preparation (2010).[6] (a) R. Snavely, M. Key, S. Hatchett, T. Cowan, M. Roth, T. Phillips, M. Stoyer, E. Henry, T. Sangser, M. Signh, S. Wilks, A. Mackinnon, A. Offenberger, D. Pennington, K. Yasuike, A. Langdon, B. Lasinski, J. Johnson, M. Perry, and E. Campbell, Intense high-energy proton beams from petawatt-laser irradiation of solids, Physical Review Letters 85, 2945 (2000).(b) S. P. Hatchett, C. G. Brown, T. E. Cowan, E. A. Henry, J. S. Johnson, M. H. Key, J. A. Koch, A. B. Langdon, B. F. Lasinski, R. W. Lee, A. J. Mackinnon, D. M. Pennington, M. D. Perry, T. W. Phillips, M. Roth, T. C. Sangster, M. S. Singh, R. A. Snavely, M. A. Stoyer, S. C. Wilks, and K. Yasuike, Electron, photon, and ion beams from the relativistic interaction of petawatt laser pulses with solid targets, Physics of Plasmas 7, 2076 (2000)

Effects of Trauma-informed Care Training on Healthcare Providers Caring for Victims of Human Trafficking

Objective: The purpose of this study is to analyze the impact of trauma-informed care training on the practice of dental, optometry, and mental health providers caring for victims of human trafficking. Methods: A mixed method approach was used, including pre-post surveys and one focus group discussion. Results: The dental, optometry, and mental health provider participants reported a greater awareness of human trafficking and greater knowledge of how to approach and care for the victims in a trauma- informed way. Conclusion: Continued training on the provision of trauma-informed care for victims of human trafficking is necessary for dentists, optometrists, and mental health professionals serving in health clinics in a university located in the southeast United States

Determinants of Specific Binding of HMGB1 Protein to Hemicatenated DNA Loops

Protein HMGB1 has long been known as one of the most abundant non-histone proteins in the nucleus of mammalian cells, and has regained interest recently for its function as an extracellular cytokine. As a DNA-binding protein, HMGB1 facilitates DNA–protein interactions by increasing the flexibility of the double helix, and binds specifically to distorted DNA structures. We have previously observed that HMGB1 binds with extremely high affinity to a novel DNA structure, hemicatenated DNA loops (hcDNA), in which double-stranded DNA fragments containing a tract of poly(CA)·poly(TG) form a loop maintained at its base by a hemicatenane. Here, we show that the single HMGB1 domains A and B, the HMG-box domain of sex determination factor SRY, as well as the prokaryotic HMGB1-like protein HU, specifically interact with hcDNA (Kd0.5 nM). However, the affinity of full-length HMGB1 for hcDNA is three orders of magnitude higher (Kd<0.5 pM) and requires the simultaneous presence of both HMG-box domains A and B plus the acidic C-terminal tail on the molecule. Interestingly, the high affinity of the full-length protein for hcDNA does not decrease in the presence of magnesium. Experiments including a comparison of HMGB1 binding to hcDNA and to minicircles containing the CA/TG sequence, binding studies with HMGB1 mutated at intercalating amino acid residues (involved in recognition of distorted DNA structures), and exonuclease III footprinting, strongly suggest that the hemicatenane, not the DNA loop, is the main determinant of the affinity of HMGB1 for hcDNA. Experiments with supercoiled CA/TG-minicircles did not reveal any involvement of left-handed Z-DNA in HMGB1 binding. Our results point to a tight structural fit between HMGB1 and DNA hemicatenanes under physiological conditions, and suggest that one of the nuclear functions of HMGB1 could be linked to the possible presence of hemicatenanes in the cell

La sépulture protohistorique de la Métairie Grande à Laure-Minervois (Aude) (VIIe s. av. n. è.)

À Laure-Minervois, entre la Montagne Noire et l’Aude, la sépulture de la Métairie Grande constitue un nouvel ensemble funéraire à rattacher au faciès Grand Bassin I. L’abondant mobilier en céramique non tournée (cratères à col et pied hauts, coupes et coupelles hémisphériques) et une épingle en fer à tête enroulée permettent de situer cette découverte dans la première moitié du VIIe s. av. J.-C. Le dépôt sépulcral a été placé dans une fosse quadrangulaire dont la fouille a montré qu’elle devait être vide de tout sédiment lors de la condamnation de la sépulture.The Métarie Grande tomb at Laure-Minervois, situated between the Montagne Noire and l'Aude, constitutes a new funerary assemblage of the Grand Bassin I facies. The large hand-thrown ceramic assemblage (crater pottery with low and high necks and feet, hemispheric cups and bowls) an iron comb with a scrolled head, allows us to place this discovery in the first half of VIIth century BC. The deposit was placed in a quadrangular ditch and the excavation showed that this must have been emptied of all sediment prior to the burial

Alternatives for sustained disaster risk reduction

The daily media is filled with images of catastrophic events which seem increasingly frequent and violent In parallel there are a large range of scientific studies debates in the policy arena, and a growing number of international institutions focused on disaster reduction. But a paradox remains that despite advances in technology, disasters continue to increase, affecting many individuals in rich as well as poor countries

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

AIM: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. METHODS: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. RESULTS: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. CONCLUSION: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state

Impact of parental lifestyle patterns in the preconception and pregnancy periods on childhood obesity

International audienceIntroduction High prevalence of overweight and obesity already observed in preschool children suggests the involvement of early-life risk factors. Preconception period and pregnancy are crucial windows for the implementation of child obesity prevention interventions with parental lifestyle factors as relevant targets. So far, most studies have evaluated their role separately, with only a few having investigated their potential synergistic effect on childhood obesity. Our objective was to investigate parental lifestyle patterns in the preconception and pregnancy periods and their association with the risk of child overweight after 5 years. Materials and methods We harmonized and interpreted results from four European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France; Elfe, France; Lifeways, Ireland; and Generation R, Netherlands] with data available for 1,900, 18,000, 1,100, and 9,500 families, respectively. Lifestyle factors were collected using questionnaires and included parental smoking, body mass index (BMI), gestational weight gain, diet, physical activity, and sedentary behavior. We applied principal component analyses to identify parental lifestyle patterns in preconception and pregnancy. Their association with risk of overweight (including obesity; OW-OB) and BMI z -scores between 5 and 12 years were assessed using cohort-specific multivariable logistic and linear and regression models (adjusted for potential confounders including parental age, education level, employment status, geographic origin, parity, and household income). Results Among the various lifestyle patterns derived in all cohorts, the two explaining the most variance were characterized by (1) “high parental smoking, low maternal diet quality (and high maternal sedentary behavior in some cohorts)” and, (2) “high parental BMI and low gestational weight gain.” Patterns characterized by high parental BMI, smoking, low diet quality or high sedentary lifestyle before or during pregnancy were associated with higher risk of OW-OB in children, and BMI z -score at any age, with consistent strengths of associations in the main cohorts, except for lifeways. Conclusion This project provides insight into how combined parental lifestyle factors in the preconception and pregnancy periods are associated with the future risk of child obesity. These findings are valuable to inform family-based and multi-behavioural child obesity prevention strategies in early life