Regulation of the Fruit-Specific PEP Carboxylase SlPPC2 Promoter at Early Stages of Tomato Fruit Development

The SlPPC2 phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) gene from tomato (Solanum lycopersicum) is differentially and specifically expressed in expanding tissues of developing tomato fruit. We recently showed that a 1966 bp DNA fragment located upstream of the ATG codon of the SlPPC2 gene (GenBank AJ313434) confers appropriate fruit-specificity in transgenic tomato. In this study, we further investigated the regulation of the SlPPC2 promoter gene by analysing the SlPPC2 cis-regulating region fused to either the firefly luciferase (LUC) or the β-glucuronidase (GUS) reporter gene, using stable genetic transformation and biolistic transient expression assays in the fruit. Biolistic analyses of 5′ SlPPC2 promoter deletions fused to LUC in fruits at the 8th day after anthesis revealed that positive regulatory regions are mostly located in the distal region of the promoter. In addition, a 5′ UTR leader intron present in the 1966 bp fragment contributes to the proper temporal regulation of LUC activity during fruit development. Interestingly, the SlPPC2 promoter responds to hormones (ethylene) and metabolites (sugars) regulating fruit growth and metabolism. When tested by transient expression assays, the chimeric promoter:LUC fusion constructs allowed gene expression in both fruit and leaf, suggesting that integration into the chromatin is required for fruit-specificity. These results clearly demonstrate that SlPPC2 gene is under tight transcriptional regulation in the developing fruit and that its promoter can be employed to drive transgene expression specifically during the cell expansion stage of tomato fruit. Taken together, the SlPPC2 promoter offers great potential as a candidate for driving transgene expression specifically in developing tomato fruit from various tomato cultivars

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Use of speckle-tracking strain in preload-dependent patients, need for cautious interpretation!

International audienceBackground: In critical patients, left ventricular ejection fraction and fractional shortening are used to reflect left ventricular systolic function. An emerging technique, two-dimensional-strain echocardiography, allows assessment of the left ventricle systolic longitudinal deformation (global longitudinal strain) and the speed at which this deformation occurs (systolic strain rate). This technique is of increasing use in critical patients in intensive care units and in the peri-operative period where preload constantly varies. Our objective, in this prospective single-center observational study, was to evaluate the effect of fluid resuscitation on two-dimensional-strain echocardiography measurements in preload-dependent critically ill patients. We included 49 patients with preload dependence attested by an increase of at least 10% in the left ventricular outflow track velocity-time integral measured by echocardiography during a passive leg raising maneuver. Echocardiography was performed before fluid resuscitation (echocardiography 1) and after preload independency achievement (echocardiography 2).Results: Two-dimensional-strain echocardiography was feasible in 40 (82%) among the 49 patients. With preload dependence correction, the absolute value of global longitudinal strain and systolic strain rate was significantly increased from, respectively, -13.3 +/- 3.5 to -18.4% +/- 4.5 (p < 0.01) and -1.11 s(-1) +/- 0.29 to -1.55 s(-1) +/- 0.55 (p < 0.001). The fluid resuscitation affects GLS and SSR in preload-dependent patients, with a shift, for GLS, from pathological to normal values.Conclusion: In critically ill patients, the assessment of the systolic function by two-dimensional-strain echocardiography needs prior evaluation of preload dependency, in order to adequately interpret this variable. Future studies should assess the ability of global longitudinal strain to guide fluid management in the critically ill patients

Vestibular inputs do not influence the fusimotor system in relaxed muscles of the human leg

Descending vestibular pathways have been shown to influence recruitment thresholds of alpha motoneurones in both human and cat. However, whereas parallel connections to the fusimotor system have been shown in the cat, such connections have not yet been demonstrated in humans. In the present study we investigated whether vestibular inputs can influence the firing of spontaneously active muscle spindles in the leg via activation of gamma motoneurones. Unitary recordings were made from 30 muscle spindle aVerents via tungsten microelectrodes inserted percutaneously into the common peroneal nerve of seated awake human subjects. Sinusoidal bipolar binaural galvanic vestibular stimulation (GVS; frequency 0.2, 0.5, 0.8 Hz, amplitude ±2 mA, 100 cycles) was applied to the mastoid processes. This continuous stimulation produced a sustained frequency-dependent illusion of “rocking in a boat” or “swinging in a hammock”. Despite these robust illusions none of the spontaneously active musclespindles exhibited phase-locked modulation of firing during sinusoidal GVS. We conclude that this dynamic vestibular input was not suYcient to recruit gamma motoneurones, which are known to have little spontaneous activity in relaxed human muscles