Transposable elements contribute to the establishment of the glycine shuttle in Brassicaceae species.

C3 -C4 intermediate photosynthesis has evolved at least five times convergently in the Brassicaceae, despite this family lacking bona fide C4 species. The establishment of this carbon concentrating mechanism is known to require a complex suite of ultrastructural modifications, as well as changes in spatial expression patterns, which are both thought to be underpinned by a reconfiguration of existing gene-regulatory networks. However, to date, the mechanisms which underpin the reconfiguration of these gene networks are largely unknown. In this study, we used a pan-genomic association approach to identify genomic features that could confer differential gene expression towards the C3 -C4 intermediate state by analysing eight C3 species and seven C3 -C4 species from five independent origins in the Brassicaceae. We found a strong correlation between transposable element (TE) insertions in cis-regulatory regions and C3 -C4 intermediacy. Specifically, our study revealed 113 gene models in which the presence of a TE within a gene correlates with C3 -C4 intermediate photosynthesis. In this set, genes involved in the photorespiratory glycine shuttle are enriched, including the glycine decarboxylase P-protein whose expression domain undergoes a spatial shift during the transition to C3 -C4 photosynthesis. When further interrogating this gene, we discovered independent TE insertions in its upstream region which we conclude to be responsible for causing the spatial shift in GLDP1 gene expression. Our findings hint at a pivotal role of TEs in the evolution of C3 -C4 intermediacy, especially in mediating differential spatial gene expression.

Impact of lockdown on cardiovascular disease hospitalizations in a Zero-COVID-19 country.

OBJECTIVES: There are concerns about the potential effect of social distancing used to control COVID-19 on the incidence of cardiovascular diseases (CVD). STUDY DESIGN: Retrospective cohort study. METHODS: We examined the association between lockdown and CVD incidence in a Zero-COVID country, New Caledonia. Inclusion criteria were defined by a positive troponin sample during hospitalization. The study period lasted for 2 months, starting March 20, 2020 (strict lockdown: first month; loose lockdown: second month) compared with the same period of the three previous years to calculate incidence ratio (IR). Demographic characteristics and main CVD diagnoses were collected. The primary endpoint was the change in incidence of hospital admission with CVD during lockdown compared with the historical counterpart. The secondary endpoint included influence of strict lockdown, change in incidence of the primary endpoint by disease, and outcome incidences (intubation or death) analyzed with inverse probability weighting method. RESULTS: A total of 1215 patients were included: 264 in 2020 vs 317 (average of the historical period). CVD hospitalizations were reduced during strict lockdown (IR 0.71 [0.58-0.88]), but not during loose lockdown (IR 0.94 [0.78-1.12]). The incidence of acute coronary syndromes was similar in both periods. The incidence of acute decompensated heart failure was reduced during strict lockdown (IR 0.42 [0.24-0.73]), followed by a rebound (IR 1.42 [1-1.98]). There was no association between lockdown and short-term outcomes. CONCLUSIONS: Our study showed that lockdown was associated with a striking reduction in CVD hospitalizations, independently from viral spread, and a rebound of acute decompensated heart failure hospitalizations during looser lockdown.

[Towards better management for sexual offenders: Presentation and conclusions of a public hearing concerning prevention, assessment, and care]. / Audition publique auteurs de violences sexuelles : prévention, évaluation, prise en charge des 14 et 15 juin 2018 : perspectives et préconisations.

In France, since the law of June 17, 1998, sexual offenders may be convicted to ambulatory mandatory care, articulated with the justice. Twenty years after the implementation of this law, while social and technological developments have redefined certain aspects of delinquency, reference documents and practice guidelines remain to be updated. This is why the professionals of the main structures and associations dealing with perpetrators of sexual violence organized a public hearing under the sponsorship of the French Federation of Resource Centers for Sexual Violence Perpetrators (FFCRIAVS) according to the methodology and with the accompaniment of the High Authority of Health. This article presents the global methodology of the public hearing "Sexual Offenders: Prevention, Evaluation and Care" which was conducted on June 14 and 15, 2018. Thirty-three experts replied to27 questions and presented their conclusions to an Audition Committee and an audience of 200 persons representative of the civil and professional society. After a public debate, the hearing committee prepared a report in which they proposed propositions in order to better care for sexual offenders.

Local pesticide use intensity conditions landscape effects on biological pest control.

Complex landscapes including semi-natural habitats are expected to favour natural enemies thereby enhancing natural pest biocontrol in crops. However, when considering a large number of situations, the response of natural biocontrol to landscape properties is globally inconsistent, a possible explanation being that local agricultural practices counteract landscape effects. In this study, along a crossed gradient of pesticide use intensity and landscape simplification, we analysed the interactive effects of landscape characteristics and local pesticide use intensity on natural biocontrol. During 3 years, using a set of sentinel prey (weed seeds, aphids and Lepidoptera eggs), biocontrol was estimated in 80 commercial fields located in four contrasted regions in France. For all types of prey excepted weed seeds, the predation rate was influenced by interactions between landscape characteristics and local pesticide use intensity. Proportion of meadow and length of interface between woods and crops had a positive effect on biocontrol of aphids where local pesticide use intensity was low but had a negative effect elsewhere. Moreover, the landscape proportion of suitable habitats for crop pests decreased the predation of sentinel prey, irrespectively of the local pesticide use intensity for weed seeds, but only in fields with low pesticide use for Lepidoptera eggs. These results show that high local pesticide use can counteract the positive expected effects of semi-natural habitats, but also that the necessary pesticide use reduction should be associated with semi-natural habitat enhancement to guarantee an effective natural biocontrol.

Midbrain circuits that set locomotor speed and gait selection.

Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed and gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). GlutNs in both of these regions contribute to the control of slower, alternating-gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed, synchronous-gait locomotion. Additionally, both the activation dynamics and the input and output connectivity matrices of GlutNs in the PPN and the CnF support explorative and escape locomotion, respectively. Our results identify two regions in the midbrain that act in conjunction to select context-dependent locomotor behaviours.

Plan delivery quality assurance for CyberKnife: Statistical process control analysis of 350 film-based patient-specific QAs.

PURPOSE: Robotic radiosurgery requires plan delivery quality assurance (DQA) but there has never been a published comprehensive analysis of a patient-specific DQA process in a clinic. We proposed to evaluate 350 consecutive film-based patient-specific DQAs using statistical process control. We evaluated the performance of the process to propose achievable tolerance criteria for DQA validation and we sought to identify suboptimal DQA using control charts. METHODS AND MATERIAL: DQAs were performed on a CyberKnife-M6 using Gafchromic-EBT3 films. The signal-to-dose conversion was performed using a multichannel-correction and a scanning protocol that combined measurement and calibration in a single scan. The DQA analysis comprised a gamma-index analysis at 3%/1.5mm and a separate evaluation of spatial and dosimetric accuracy of the plan delivery. Each parameter was plotted on a control chart and control limits were calculated. A capability index (Cpm) was calculated to evaluate the ability of the process to produce results within specifications. RESULTS: The analysis of capability showed that a gamma pass rate of 85% at 3%/1.5mm was highly achievable as acceptance criteria for DQA validation using a film-based protocol (Cpm>1.33). 3.4% of DQA were outside a control limit of 88% for gamma pass-rate. The analysis of the out-of-control DQA helped identify a dosimetric error in our institute for a specific treatment type. CONCLUSION: We have defined initial tolerance criteria for DQA validations. We have shown that the implementation of a film-based patient-specific DQA protocol with the use of control charts is an effective method to improve patient treatment safety on CyberKnife.

CyberKnife® M6™: Peripheral dose evaluation for brain treatments.

PURPOSE: This study evaluates the peripheral dose (PD) delivered to healthy tissues for brain stereotactic radiotherapy treatments (SRT) performed with a CyberKnife M6™ Robotic Radiosurgery System and proposes a model to estimate PD before treatment. METHOD: PD was measured with thermoluminescent dosimeters. Measurements were performed to evaluate the influence of distance, collimator type (fixed or Iris™) and aperture size on PD for typical brain treatment plans simulated on an anthropomorphic phantom. A model to estimate PD was defined by fitting functions to these measurements. In vivo measurements were subsequently performed on 30 patients and compared to the model-predicted PD. RESULTS: PD (in cGy) was about 0.06% of MU at 15cm for a 20mm fixed collimator and 0.04% of MU for the same aperture with Iris™ collimator. In vivo measurements showed an average thyroid dose of 55mGy (σ=18.8mGy). Computed dose for thyroid, breast, umbilicus and gonads showed on average a relative difference of 3.4% with the in vivo dose (σ=12.4%). CONCLUSION: PD at the thyroid with Iris™ was about a third lower than with a fixed collimator in case of brain SRT. Despite uncertainties (use of anthropomorphic PD to estimate patient specific PD, surface PD to estimate OAR PD) the model allows PD to be estimated without in vivo measurements. This method could be used to optimise PD with different planning strategies.

A hot Jupiter orbiting a 2-million-year-old solar-mass T Tauri star.

Hot Jupiters are giant Jupiter-like exoplanets that orbit their host stars 100 times more closely than Jupiter orbits the Sun. These planets presumably form in the outer part of the primordial disk from which both the central star and surrounding planets are born, then migrate inwards and yet avoid falling into their host star. It is, however, unclear whether this occurs early in the lives of hot Jupiters, when they are still embedded within protoplanetary disks, or later, once multiple planets are formed and interact. Although numerous hot Jupiters have been detected around mature Sun-like stars, their existence has not yet been firmly demonstrated for young stars, whose magnetic activity is so intense that it overshadows the radial velocity signal that close-in giant planets can induce. Here we report that the radial velocities of the young star V830 Tau exhibit a sine wave of period 4.93 days and semi-amplitude 75 metres per second, detected with a false-alarm probability of less than 0.03 per cent, after filtering out the magnetic activity plaguing the spectra. We find that this signal is unrelated to the 2.741-day rotation period of V830 Tau and we attribute it to the presence of a planet of mass 0.77 times that of Jupiter, orbiting at a distance of 0.057 astronomical units from the host star. Our result demonstrates that hot Jupiters can migrate inwards in less than two million years, probably as a result of planet­disk interactions.

Functional imaging of cerebral perfusion.

The functional imaging of perfusion enables the study of its properties such as the vasoreactivity to circulating gases, the autoregulation and the neurovascular coupling. Downstream from arterial stenosis, this imaging can estimate the vascular reserve and the risk of ischemia in order to adapt the therapeutic strategy. This method reveals the hemodynamic disorders in patients suffering from Alzheimer's disease or with arteriovenous malformations revealed by epilepsy. Functional MRI of the vasoreactivity also helps to better interpret the functional MRI activation in practice and in clinical research.

Multiscale structures of lipids in foods as parameters affecting fatty acid bioavailability and lipid metabolism.

On a nutritional standpoint, lipids are now being studied beyond their energy content and fatty acid (FA) profiles. Dietary FA are building blocks of a huge diversity of more complex molecules such as triacylglycerols (TAG) and phospholipids (PL), themselves organised in supramolecular structures presenting different thermal behaviours. They are generally embedded in complex food matrixes. Recent reports have revealed that molecular and supramolecular structures of lipids and their liquid or solid state at the body temperature influence both the digestibility and metabolism of dietary FA. The aim of the present review is to highlight recent knowledge on the impact on FA digestion, absorption and metabolism of: (i) the intramolecular structure of TAG; (ii) the nature of the lipid molecules carrying FA; (iii) the supramolecular organization and physical state of lipids in native and formulated food products and (iv) the food matrix. Further work should be accomplished now to obtain a more reliable body of evidence and integrate these data in future dietary recommendations. Additionally, innovative lipid formulations in which the health beneficial effects of either native or recomposed structures of lipids will be taken into account can be foreseen.

Evaluation of dual-source parallel RF excitation technology in MRI of thoraco-lumbar spine at 3.0 T.

High-field 3 T magnetic resonance imaging (MRI) has entered standard clinical practice over the past decade, and its advantages have already been suggested in areas such as neural, musculoskeletal, pelvic and angiographic imaging. However, high-field systems still pose challenges in terms of their specific absorption rate (SAR) and radiofrequency (RF) excitation uniformity. Thus, the aim of the present study was to evaluate the impact, on both these factors, of standard quadrature against parallel RF transmission technology (dual-source parallel RF excitation [DSPE]) in spinal examination at 3 T. The thoracolumbar spine was examined with three different sequences: T1-weighted (T1w); T2-weighted (T2w); and T2w short tau inversion recovery (STIR). Each was acquired with and without DSPE. The manufacturer's implementation of this technology has been associated with optimized handling of patient SAR exposure, resulting in a 38.4% reduction in acquisition time. On comparing sequences with equal repetition times (TRs), the acquisition time reduction was 44.4%. Thus, DSPE allows a reduction in acquisition time. This gain is accompanied by augmentation of the whole-body SAR and diminution of the local SAR. Image quality improvement due to more homogeneous effective transmit B1 was mainly observed at the junction of the thoracolumbar spine.

Per-subject characterization of bolus width in pulsed arterial spin labeling using bolus turbo sampling.

Quantification of cerebral blood flow using QUIPSSII pulsed arterial spin labeling requires that the QUIPSS saturation delay TI1 is shorter than the natural temporal bolus width. Yet the duration of the bolus of tagged spins entering the region of interest varies during vasoactive stimuli such as gaseous challenges or across subjects due to differences in blood velocity or vessel geometry. A new technique, bolus turbo sampling, to rapidly measure the duration of the inflowing bolus is presented. It allows to optimize the arterial spin labeling acquisition to ensure reliable quantification of perfusion while maximizing the arterial spin labeling signal by avoiding the use of unnecessarily short label durations. The average bolus width measured in the right and left middle cerebral artery territories using the bolus turbo sampling technique has a repeatability coefficient of 75 ms and correlates significantly with the TI1,max determined from a novel multi-TI1 protocol (R=0.65, P<0.05). The possibility to measure the bolus width under hypercapnia is demonstrated.

Use of the Larval Tarsal Test to determine acaricide resistance in Rhipicephalus (Boophilus) microplus Brazilian field populations.

Acaricide resistance of the cattle tick Rhipicephalus (Boophilus) microplus is widespread in most of the countries where this parasite is present. Bioassays are used to diagnose the level and pattern of resistance in tick populations. In the present study, we describe a detailed protocol of the Larval Tarsal Test (LTT) using simplified equipment and data on the resistance of 17 tick field populations originating from 5 Brazilian states. Nine acaricidal compounds from 5 major classes were tested: organophosphates (OP), synthetic pyrethroids (SP), macrocyclic lactones (ML), phenylpyrazols (PYZ) and amidines. For comparison, four of the tick populations were also tested with the Larval Packet Test (LPT) with one compound per class. The most common resistances were to SP, amitraz and OP, with frequencies of 94%, 88% and 82%, respectively. Resistance to PYZ was also found to be widespread (65%), suggesting a rapid development of fipronil resistance in Brazil. One case of ML resistance and 2 cases of suspected ML resistance were identified with the LTT. The LTT led to higher resistance ratios to all compounds than the LPT, reflecting its high sensitivity to detect resistance. Finally, the LTT allowed testing a larger number of compounds and doses with reduced labour in comparison to the LPT and turned out to be a reliable bioassay to detect resistance in field populations.

A new in vitro test to evaluate the resistance level against acaricides of the cattle tick, Rhipicephalus (Boophilus) microplus.

In this article we present a new bioassay to assess the resistance status of ticks to acaricides. The Larval Tarsal Test (LTT) is a sensitive, highly time-effective in vitro test. It allows the investigation of a large number of compounds and doses on the cattle tick Rhipicephalus (Boophilus) microplus in a short period of time. The ability of the LTT to assess the lethal concentration at 50% mortality (LC(50)) and resistance ratios (RRs) of a susceptible and a resistant R. microplus strain was compared with the FAO-recommended Larval Packet Test (LPT). Representative compounds of the carbamate, organophosphate (OP), synthetic pyrethroid (SP), formamidine (FOR), macrocyclic lactone and pyrazole classes were used for this comparison. The resistance status against OP, SP and FOR of the resistant R. microplus strain was confirmed in vivo. The LTT resulted in resistance ratios comparable to those obtained with the LPT. However, the lethal concentrations were up to 150-fold lower in the LTT than in the LPT. The advantage of the LTT is to simplify the methodology by avoiding the handling of larvae and using multi-well plates. The LTT is therefore a suitable test for the assessment of the level of resistance of R. microplus and is very promising to evaluate the resistance profile of field strains. Additionally, the LTT is also suitable to test other ixodid species.

Bis(monoacylglycero)phosphate, a peculiar phospholipid to control the fate of cholesterol: Implications in pathology.

Bis(monoacylglycero)phosphate (BMP) is a structural isomer of phosphatidylglycerol that exhibits an unusual sn1:sn1' stereoconfiguration, based on the position of the phosphate moiety on its two glycerol units. Early works have underlined the high concentration of BMP in the lysosomal compartment, especially during some lysosomal storage disorders and drug-induced phospholipidosis. Despite numerous studies, both biosynthetic and degradative pathways of BMP remained not completely elucidated. More recently, BMP has been localized in the internal membranes of late endosomes where it forms specialized lipid domains. Its involvement in both dynamics and lipid/protein sorting functions of late endosomes has started to be documented, especially in the control of cellular cholesterol distribution. BMP also plays an important role in the late endosomal/lysosomal degradative pathway. Another peculiarity of BMP is to be naturally enriched in docosahexaenoic acid and/or to specifically incorporate this fatty acid compared to other polyunsaturated fatty acids, which may confer specific biophysical and functional properties to this phospholipid. This review summarizes and updates our knowledge on BMP with an emphasis on its possible implication in human health and diseases, especially in relation to cholesterol homeostasis.

Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep.

The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.

Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate.

Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate.

Implementation of in-line infrared monitor in full-scale anaerobic digestion process.

During start up but also during normal operation, anaerobic reactor systems should be run and monitored carefully to secure trouble-free operation, because the process is vulnerable to disturbances such as temporary overloading, biomass wash out and influent toxicity. The present method of monitoring is usually by manual sampling and subsequent laboratory analysis. Data collection, processing and feedback to system operation is manual and ad hoc, and involves high-level operator skills and attention. As a result, systems tend to be designed at relatively conservative design loading rates resulting in significant over-sizing of reactors and thus increased systems cost. It is therefore desirable to have on-line and continuous access to performance data on influent and effluent quality. Relevant variables to indicate process performance include VFA, COD, alkalinity, sulphate, and, if aerobic post-treatment is considered, total nitrogen, ammonia and nitrate. Recently, mid-IR spectrometry was demonstrated on a pilot scale to be suitable for in-line simultaneous measurement of these variables. This paper describes a full-scale application of the technique to test its ability to monitor continuously and without human intervention the above variables simultaneously in two process streams. For VFA, COD, sulphate, ammonium and TKN good agreement was obtained between in-line and manual measurements. During a period of six months the in-line measurements had to be interrupted several times because of clogging. It appeared that the sample pre-treatment unit was not able to cope with high solids concentrations all the time.

[Acute myocardial infarction in myocardial bridge treated by coronary stent]. / Infarctus du myocarde aigu sur pont myocardique traité par l'implantation d'endoprothèses. Résultats immédiats et suivi à long terme.

The authors report the case of a symptomatic myocardial bridge treated in the acute phase of anterior wall myocardial infarction by classical stenting of the mid and distal left anterior descending artery. One and a half months later, intrastent restenosis at the two dilated sites, led to another angioplasty procedure with implantation of sirolimus-eluding stents. The outcome was good with no recurrence of angina at 16 months and control coronary angiography was totally normal at the 8th month.