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

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

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

Evaluation of Hemoglobin A1c Criteria to Assess Preoperative Diabetes Risk in Cardiac Surgery Patients

Objective: Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Methods: Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. Results: All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. Conclusions: In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90436/1/dia-2E2011-2E0074.pd

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

Interaction of high energy protons in nuclear emulsions loaded with b 10 and LiF

An experiment is proposed to expose nuclear emulsions loaded with B{sup 10} and LiF to high energy protons at 100 GeV, 150 GeV and 200 GeV. The purposes are: (i) to measure the total cross-sections at these incident energies, (ii) to investigate charged multiplicity as a function of energy, (iii) to investigate the angular distribution and development of hadron showers in collisions of protons with nuclei

Mn bioavailability by polarized Caco-2 cells: comparison between Mn gluconate and Mn oxyprolinate

<p>Abstract</p> <p>Background</p> <p>Micronutrient inadequate intake is responsible of pathological deficiencies and there is a need of assessing the effectiveness of metal supplementation, frequently proposed to rebalance poor diets. Manganese (Mn) is present in many enzymatic intracellular systems crucial for the regulation of cell metabolism, and is contained in commercially available metal supplements.</p> <p>Methods</p> <p>We compared the effects of two different commercial Mn forms, gluconate (MnGluc) and oxyprolinate (MnOxP). For this purpose we used the polarized Caco-2 cells cultured on transwell filters, an established in vitro model of intestinal epithelium. Since micronutrient deficiency may accelerate mitochondrial efficiency, the mitochondrial response of these cells, in the presence of MnGluc and MnOxP, by microscopy methods and by ATP luminescence assay was used.</p> <p>Results</p> <p>In the presence of both MnOxP and MnGluc a sustained mitochondrial activity was shown by mitoTraker labeling (indicative of mitochondrial respiration), but ATP intracellular content remained comparable to untreated cells only in the presence of MnOxP. In addition MnOxP transiently up-regulated the antioxidant enzyme Mn superoxide dismutase more efficiently than MnGluc. Both metal treatments preserved NADH and βNADPH diaphorase oxidative activity, avoided mitochondrial dysfunction, as assessed by the absence of a sustained phosphoERK activation, and were able to maintain cell viability.</p> <p>Conclusions</p> <p>Collectively, our data indicate that MnOxP and MnGluc, and primarily the former, produce a moderate and safe modification of Caco-2 cell metabolism, by activating positive enzymatic mechanisms, thus could contribute to long-term maintenance of cell homeostasis.</p

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig

A phase II irinotecan–cisplatin combination in advanced pancreatic cancer

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS&gt;70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity