Engineering a catabolic pathway in plants for the degradation of 1,2-dichloroethane

Plants are increasingly being employed to clean up environmental pollutants such as heavy metals; however, a major limitation of phytoremediation is the inability of plants to mineralize most organic pollutants. A key component of organic pollutants is halogenated aliphatic compounds that include 1,2-dichloroethane (1,2-DCA). Although plants lack the enzymatic activity required to metabolize this compound, two bacterial enzymes, haloalkane dehalogenase (DhlA) and haloacid dehalogenase (DhlB) from the bacterium Xanthobacter autotrophicus GJ10, have the ability to dehalogenate a range of halogenated aliphatics, including 1,2-DCA. We have engineered the dhlA and dhlB genes into tobacco (Nicotiana tabacum ‘Xanthi’) plants and used 1,2-DCA as a model substrate to demonstrate the ability of the transgenic tobacco to remediate a range of halogenated, aliphatic hydrocarbons. DhlA converts 1,2-DCA to 2-chloroethanol, which is then metabolized to the phytotoxic 2-chloroacetaldehyde, then chloroacetic acid, by endogenous plant alcohol dehydrogenase and aldehyde dehydrogenase activities, respectively. Chloroacetic acid is dehalogenated by DhlB to produce the glyoxylate cycle intermediate glycolate. Plants expressing only DhlA produced phytotoxic levels of chlorinated intermediates and died, while plants expressing DhlA together with DhlB thrived at levels of 1,2-DCA that were toxic to DhlA-expressing plants. This represents a significant advance in the development of a low-cost phytoremediation approach toward the clean-up of halogenated organic pollutants from contaminated soil and groundwater

In the back of your mind: Cortical mapping of paraspinal afferent inputs

Topographic organisation is a hallmark of vertebrate cortex architecture, characterised by ordered projections of the body's sensory surfaces onto brain systems. High-resolution functional magnetic resonance imaging (fMRI) has proven itself as a valuable tool to investigate the cortical landscape and its (mal-)adaptive plasticity with respect to various body part representations, in particular extremities such as the hand and fingers. Less is known, however, about the cortical representation of the human back. We therefore validated a novel, MRI-compatible method of mapping cortical representations of sensory afferents of the back, using vibrotactile stimulation at varying frequencies and paraspinal locations, in conjunction with fMRI. We expected high-frequency stimulation to be associated with differential neuronal activity in the primary somatosensory cortex (S1) compared with low-frequency stimulation and that somatosensory representations would differ across the thoracolumbar axis. We found significant differences between neural representations of high-frequency and low-frequency stimulation and between representations of thoracic and lumbar paraspinal locations, in several bilateral S1 sub-regions, and in regions of the primary motor cortex (M1). High-frequency stimulation preferentially activated Brodmann Area (BA) regions BA3a and BA4p, whereas low-frequency stimulation was more encoded in BA3b and BA4a. Moreover, we found clear topographic differences in S1 for representations of the upper and lower back during high-frequency stimulation. We present the first neurobiological validation of a method for establishing detailed cortical maps of the human back, which might serve as a novel tool to evaluate the pathological significance of neuroplastic changes in clinical conditions such as chronic low back pain

Wireless sensor web for rover planetary exploration

Together with the “traditional“ approach, during the last years a new concept of planetary surface exploration has been introduced and investigated by the space community, including the European Space Agency (ESA). The concept consists in deploying a number of sensors communicating among themselves in a wireless networked architecture (WSN). These sensors, altogether, constitute a distributed instrument with the potential of broadening the capabilities of making science on and around a planetary body. When compared to big and monolithic planetary probes, with payloads able to obtain high-quality local measurements (e.g. by imaging or sampling), wireless sensor networks allow mapping larger planetary surfaces and/or volumes over a large time span. This concept is particularly suitable to retrieve localised simple measurements such as pressure, temperature, humidity or gas type, which could support the major interests of space exploration: 1) determine if life ever arose on a certain celestial body, 2) characterise the geology and topology of the body surface, 3) characterise its climate, and 4) prepare for human exploration. In line with this trend ESA initiated the RF-WIPE project (RF Wireless for Planetary Exploration), with GMV leading a consortium completed by SUPSI (University of Applied Sciences and Arts of Southern Switzerland) and UPM (Technical University of Madrid

Reduced salivary oxytocin after an empathic induction task in Intimate Partner Violence perpetrators: Importance of socio-affective functions and its impact on prosocial behavior

Intimate Partner Violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial behavior. Thus, the study of salivary OXT (sOXT) may provide further information about potential impairments in social cognition in IPV perpetrators. This study analyzed the effects of an empathic induction task, performed through negative emotion-eliciting videos, on endogenous sOXT levels, mood state, and emotional perception in 30 IPV perpetrators compared to 32 controls. Additionally, we explored their performance on prosocial behavior after the empathic induction task, using Hare''s donation procedure. Lower sOXT levels were found in IPV perpetrators after the task compared to controls, along with a general decreasing tendency in their sOXT levels. Additionally, IPV perpetrators exhibited no change in their mood state and perceived others'' emotions as more positive and less intense. Moreover, the mood state response and alexithymia traits, respectively, positively and negatively predicted the sOXT levels after the empathic induction task in the entire sample. Finally, we did not observe a lower appearance of prosocial behaviors in IPV perpetrators; however, higher sOXT levels after the empathic induction task were found in subjects who donated when considering the whole sample. In sum, IPV perpetrators exhibited differences in their sOXT levels when empa-thizing, compared to controls, with alexithymia and the emotional response potentially explaining the sOXT levels after the task. Furthermore, prosocial behavior was more related to these sOXT levels than to IPV. As our knowledge about the emotional processing of IPV perpetrators increases, we will be better able to develop and include coadjutant treatments in current psychotherapeutic programs, in order to focus on their emotional needs, which, in turn, would reduce the future risk of recidivism

Analysis of results of effective dose estimation obtained from RADAR 2017 dose assessment model for nuclear medicine procedures

EP-296 Aim/Introduction: To analyze the results of effective dose (E) estimation of the most frequent procedures using photon emitters in Nuclear Medicine, obtained from RADAR 2017 dose assessment model. To compare these results with those obtained from ICRP 128 (2015) recommendations, and to assess how using each dose assessment model can change E results. Materials and Methods: E estimation data was collected from photon emitter procedures performed during the last year in our department, obtained from RADAR 2017 dose estimation model for age groups: = 1 year old; >1-5 years old ; >5- 10 years old, >10- 15 years old and adults. Injected activity was the one recommended by international guidelines and EANM Pediatric and Dosimetry Committees. Hybrid exams (SPECT / CT) and procedures for which there is no RADAR 2017 dosimetry estimation were excluded. Results for (E) were compared with those obtained by using ICRP 128 (2015) recommendations. Results: With RADAR 2017 dose evaluation model we obtained a lower mean value of E on most of the procedures that were analyzed, being significantly lower for Renogram, Renal scintigraphy on >10-15 years old, Thyroid scintigraphy, Meckel’s scan and Bone Scan (0.12 to 1.16 mSv, 25% to 67%). Brain perfusion and Renal scintigraphy on ages under 10 obtained a significantly greater difference for E (0.33 to 2.85 mSv, 26% to 29%). Conclusion: These results are an updated collection of estimated E values for photon-emitting radiopharmaceuticals commonly used in Nuclear Medicine, considering RADAR 2017 dose assessment model compared to ICRP 128) recommendations. Methodological changes on estimation lead to lower E for most of diagnostic procedures using photon emitters, this is of special interest for patients undergoing repeated ionizing radiation (dosimetry history)

Why Were More Than 200 Subjects Required to Demonstrate the Bioequivalence of a New Formulation of Levothyroxine with an Old One?

At the request of French Regulatory Authorities, a new formulation of Levothyrox® was licensed in France in 2017, with the objective of avoiding the stability deficiencies of an existing licensed formulation. Before launching the new formulation, an average bioequivalence (ABE) trial was conducted, having enrolled 204 subjects and selected for interpretation a narrow a priori bioequivalence range of 0.90–1.11. Bioequivalence was concluded. In a previous publication, we questioned the ability of an ABE trial to guarantee the switchability within patients of the new and old levothyroxine formulations. It was suggested that the two formulations should be compared using the conceptual framework of individual bioequivalence. The present paper is a response to those claiming that, despite the fact that ABE analysis does not formally address the switchability of the two formulations, future patients will nevertheless be fully protected. The basis for this claim is that the ABE study was established in a large trial and analyzed using a stringent a priori acceptance interval of equivalence. These claims are questionable, because the use of a very large number of subjects nullifies the implicit precautionary intention of the European guideline when, for a Narrow Therapeutic Index drug, it recommends shortening the a priori acceptance interval from 0.80–1.25 to 0.90–1.11

Elucidating the role of shape anisotropy in faceted magnetic nanoparticles using biogenic magnetosomes as a model

Shape anisotropy is of primary importance to understand the magnetic behavior of nanoparticles, but a rigorous analysis in polyhedral morphologies is missing. In this work, a model based on finite element techniques has been developed to calculate the shape anisotropy energy landscape for cubic, octahedral, and truncated octahedral morphologies. In all cases, a cubic shape anisotropy is found that evolves to quasi uniaxial anisotropy when the nanoparticle is elongated amp; 8805;2 . This model is tested on magnetosomes, amp; 8764;45 nm truncated octahedral magnetite nanoparticles forming a chain inside Magnetospirillum gryphiswaldense MSR 1 bacteria. This chain presents a slightly bent helical configuration due to a 20 tilting of the magnetic moment of each magnetosome out of chain axis. Electron cryotomography images reveal that these magnetosomes are not ideal truncated octahedrons but present amp; 8776;7.5 extrusion of one of the 001 square faces and amp; 8776;10 extrusion of an adjacent 111 hexagonal face. Our model shows that this deformation gives rise to a quasi uniaxial shape anisotropy, a result of the combination of a uniaxial Ksh u 7 kJ m amp; 8722;3 and a cubic Ksh c 1.5 kJ m amp; 8722;3 contribution, which is responsible for the 20 tilting of the magnetic moment. Finally, our results have allowed us to accurately reproduce, within the framework of the Landau Lifshitz Gilbert model, the experimental AC loops measured for these magnetotactic bacteri

Tuning the Magnetic Response of Magnetospirillum magneticum by Changing the Culture Medium A Straightforward Approach to Improve Their Hyperthermia Efficiency

Magnetotactic bacteria Magnetospirillum magneticum AMB 1 have been cultured using three different media magnetic spirillum growth medium with Wolfe s mineral solution MSGM W , magnetic spirillum growth medium without Wolfe s mineral solution MSGM W , and flask standard medium FSM . The influence of the culture medium on the structural, morphological, and magnetic characteristics of the magnetosome chains biosynthesized by these bacteria has been investigated by using transmission electron microscopy, X ray absorption spectroscopy, and X ray magnetic circular dichroism. All bacteria exhibit similar average size for magnetosomes, 40 45 nm, but FSM bacteria present slightly longer subchains. In MSGM W bacteria, Co2 ions present in the medium substitute Fe2 ions in octahedral positions with a total Co doping around 4 5 . In addition, the magnetic response of these bacteria has been thoroughly studied as functions of both the temperature and the applied magnetic field. While MSGM W and FSM bacteria exhibit similar magnetic behavior, in the case of MSGM W, the incorporation of the Co ions affects the magnetic response, in particular suppressing the Verwey amp; 8764;105 K and low temperature amp; 8764;40 K transitions and increasing the coercivity and remanence. Moreover, simulations based on a Stoner Wolhfarth model have allowed us to reproduce the experimentally obtained magnetization versus magnetic field loops, revealing clear changes in different anisotropy contributions for these bacteria depending on the employed culture medium. Finally, we have related how these magnetic changes affect their heating efficiency by using AC magnetometric measurements. The obtained AC hysteresis loops, measured with an AC magnetic field amplitude of up to 90 mT and a frequency, f, of 149 kHz, reveal the influence of the culture medium on the heating properties of these bacteria below 35 mT, MSGM W bacteria are the best heating mediators, but above 60 mT, FSM and MSGM W bacteria give the best heating results, reaching a maximum heating efficiency or specific absorption rate SAR of SAR f amp; 8776; 12 W g 1 kHz

Levothyrox® new and old formulations: are they switchable for millions of patients?

International audienceIn France, more than 2.5 million patients are currently treated with levothyroxine, mainly as the marketed product Levothyrox ®. In March 2017, at the request of French authorities, a new formulation of Levothyrox ® was licensed, with the objective of avoiding stability deficiencies of the old formulation. Before launching this new formulation, an average bioequivalence trial, based on European Union recommended guidelines, was performed. The implicit rationale was the assumption that the two products, being bioequivalent, would also be switchable, allowing substitution of the new for the old formulation, thus avoiding the need for individual calibration of the dosage regimen of thyroxine, using the thyroid-stimulating hormone level as the endpoint, as required for a new patient on initiating treatment. Despite the fact that both formulations were shown to be bioequivalent, adverse drug reactions were reported in several thousands of patients after taking the new formulation. In this opinion paper, we report that more than 50% of healthy volunteers enrolled in a successful regulatory average bioequivalence trial were actually outside the a priori bioequivalence range. Therefore, we question the ability of an average bioequivalence trial to guarantee the switchability within patients of the new and old levothyroxine formulations. We further propose an analysis of this problem using the conceptual framework of individual bioequivalence. This involves investigating the bioavailability of the two formulations within a subject, by comparing not only the population means (as established by average bioequivalence) but also by assessing two variance terms, namely the within-subject variance and the variance estimating subject-by-formulation interaction. A higher within individual variability for the new formulation would lead to reconsideration of the appropriateness of the new formulation. Alternatively, a possible subject-by-formulation interaction would allow a judgement on the ability, or not, of doctors to manage patients effectively during transition from the old to the new formulation