Setdb1 protects genome integrity in murine muscle stem cells to allow for regenerative myogenesis and inflammation.

The histone H3 lysine 9 methyltransferase SETDB1 controls transcriptional repression to direct stem cell fate. Here, we show that Setdb1 expression by adult muscle stem cells (MuSCs) is required for skeletal muscle regeneration. We find that SETDB1 represses the expression of endogenous retroviruses (ERVs) in MuSCs. ERV de-repression in Setdb1-null MuSCs prevents their amplification following exit from quiescence and promotes cell death. Multi-omics profiling shows that chromatin decompaction at ERV loci activates the DNA-sensing cGAS-STING pathway, entailing cytokine expression by Setdb1-null MuSCs. This is followed by aberrant infiltration of inflammatory cells, including pathological macrophages. The ensuing histiocytosis is accompanied by myofiber necrosis, which, in addition to progressive MuSCs depletion, completely abolishes tissue repair. In contrast, loss of Setdb1 in fibro-adipogenic progenitors (FAPs) does not impact immune cells. In conclusion, genome maintenance by SETDB1 in an adult somatic stem cell is necessary for both its regenerative potential and adequate reparative inflammation.

Torsion of the spermatic cord revealing cystic dysplasia of the testicle.

Cystic dysplasia of the testis is characterized by the presence of multiple cysts within the testicular parenchyma. It is a rare benign tumor. It is often accompanied by kidney malformations. There is no consensus on treatment. We report here the case of testicular dysplasia revealed by a torsion of the spermatic cord in an adult. The diagnosis of cystic dysplasia of the testis was made intraoperatively and confirmed by pathology. An orchiectomy was performed. Serum testicular cancer markers were normal postoperatively.

Real-time phase contrast MRI versus conventional phase contrast MRI at different spatial resolutions and velocity encodings.

PURPOSES: To compare the accuracy of real-time phase-contrast echo-planar MRI (EPI-PC) and conventional cine phase-contrast MRI (Conv-PC) and to assess the influence of spatial resolutions (pixel size) and velocity encoding on flow measurements obtained with the two sequences. METHODS: Flow quantification was assessed using a pulsatile flow phantom (diameter: 9.5 mm; mean flow rate: 1150 mm3/s; mean flow velocity: 1.6 cm/s). Firstly, the accuracy of the EPI-PC was checked by comparing it with the flow rate in the calibrated phantom and the pulsation index from Conv-PC. Secondly, flow data from the two sequences were compared quantitatively as a function of the pixel size and the velocity encoding. RESULTS: The mean percentage difference between the EPI-PC flow rate and calibrated phantom flow rate was -2.9 ± 2.1% (Mean ± SD). The pulsatility indices for EPI-PC and Conv-PC were respectively 0.64 and 0.59. In order to keep the flow rate measurement error within 10%, the ROI in Conv-PC had to contain at least 13 pixels, while the ROI in EPI-PC had to contain at least 9 pixels. Furthermore, Conv-PC had a higher velocity-to-noise ratio and could use a higher velocity encoding than EPI-PC (20 cm/s and 15 cm/s, respectively). CONCLUSIONS: The result of this in vitro study confirmed the accuracy of EPI-PC, and found that EPI-PC can adapt to lower spatial resolutions, but is more sensitive to velocity encoding than Conv-PC.

Use of real-time phase-contrast MRI to quantify the effect of spontaneous breathing on the cerebral arteries.

Quantification of the effect of breathing on the cerebral circulation provides a better mechanistic understanding of the brain's circulatory system and is important in the early diagnosis of certain neurological diseases. However, conventional cine phase-contrast (CINE-PC) MRI cannot be used in this field of study because it only provides an average cardiac cycle flow curve reconstructed from multiple cardiac cycles. Unlike CINE-PC, phase-contrast echo-planar imaging (EPI-PC) can be used to quantify the blood flow rate in "real-time" and thus assess the effect of breathing on blood flow. Here, we first used post-processing software (developed in-house) to determine the feasibility of quantifying cerebral arterial blood flow with EPI-PC (relative to CINE-PC) in 16 participants. In a second step, we developed a new time-domain method for quantifying the intensity and the phase shift of the effects of breathing on the mean flow rate, stroke volume, cardiac period and amplitude of cerebral blood flow (in 10 participants). Our results showed that EPI-PC can quantify cerebral arterial blood flow rate with much the same degree of accuracy as CINE-PC but is more strongly influenced by differences in magnetic susceptibility. We found that breathing affected the mean flow rate, stroke volume and cardiac period of cerebral arterial blood flow.

Effects of Methylphenidate on Default-Mode Network/Task-Positive Network Synchronization in Children With ADHD.

OBJECTIVE: A failure of the anti-phase synchronization between default-mode (DMN) and task-positive networks (TPN) may be involved in a main manifestation of ADHD: moment-to-moment variability. The study investigated whereby methylphenidate may improve TPN/DMN synchronization in ADHD. METHOD: Eleven drug-naive ADHD children and 11 typically developing (TD) children performed a flanker task during functional magnetic resonance imaging. The ADHD group was scanned without and 1 month later with methylphenidate. The signal was analyzed by independent component analysis. RESULTS: The TD group showed anti-phase DMN/TPN synchronization. The unmedicated ADHD group showed synchronous activity in the posterior DMN only, which was positively correlated with response time variability for the flanker task. Methylphenidate initiated a partial anti-phase TPN/DMN synchronization, reduced variability, and abolished the variability/DMN correlation. CONCLUSION: Although results should be interpreted cautiously because the sample size is small, they suggest that a failure of the TPN/DMN synchronization could be involved in the moment-to-moment variability in ADHD. Methylphenidate initiated TPN/DMN synchronization, which in turn appeared to reduce variability.

Individual differences in subcortical microstructure organization reflect reaction time performances during a flanker task: a diffusion tensor imaging study in children with and without ADHD.

The results of several previous magnetic resonance imaging studies suggest that the fronto-striato-thalamic circuitry is involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, few studies have investigated the putative association between quantitative diffusion tensor imaging measurements of subcortical gray matter and subject task performances in children with ADHD. Here, we examined whether reaction time (RT) parameters during a flanker task were correlated with mean diffusivity (MD) measurements in the basal ganglia and thalamus in children with ADHD and in controls. For the study group as a whole, both the mean RT and the intra-individual variability in RTs were found to be significantly correlated with MD measurements in the right and left caudate, putamen and thalamus. In contrast, the correlation between the interference effect and MD failed to reach statistical significance. The present results may advance our understanding of the anatomical substrates of ADHD.

Dysfunction of the attentional brain network in children with Developmental Coordination Disorder: a fMRI study.

Children with Developmental Coordination Disorder (DCD) present impaired motor skills, frequently associated with impaired attentional and executive functions. The objective of this study was to assess the impact of DCD on effective connectivity applied to a putative model of inhibition. fMRI was performed in 9 children with DCD and 10 control children (8-13 years old) performing a go-nogo task. As previously reported, children with DCD obtained a similar score for correct inhibitions as controls, but responses were slower and more variable than in controls. Compared to controls, Structural Equation Modeling indicated that: (1) path coefficients from both middle frontal cortex (MFC) and anterior cingulate cortex (ACC) to inferior parietal cortex (IPC) increased in children with DCD particularly in the left hemisphere; (2) path coefficients between striatum and parietal cortex decreased in children with DCD in the right hemisphere. Results suggest that DCD could be characterized by abnormal brain hemispheric specialization during development. Furthermore, connectivity in the MFC-ACC-IPC network could indicate that children with DCD are less able than healthy children to easily and/or promptly switch between go and nogo motor responses. However, children with DCD seem to compensate for this poor efficiency by more actively engaging the ACC to prevent commissions allowing maintenance of a good level of inhibition.

A new lumped-parameter model of cerebrospinal hydrodynamics during the cardiac cycle in healthy volunteers.

Our knowledge of cerebrospinal fluid (CSF) hydrodynamics has been considerably improved with the recent introduction of phase-contrast magnetic resonance imaging (phase-contrast MRI), which can provide CSF and blood flow measurements throughout the cardiac cycle. Key temporal and amplitude parameters can be calculated at different sites to elucidate the role played by the various CSF compartments during vascular brain expansion. Most of the models reported in the literature do not take into account CSF oscillation during the cardiac cycle and its kinetic energy impact on the brain. We propose a new lumped-parameter compartmental model of CSF and blood flows in healthy subjects during the cardiac cycle. The system was divided into five submodels representing arterial blood, venous blood, ventricular CSF, cranial subarachnoid space, and spinal subarachnoid space. These submodels are connected by resistances and compliances. The model developed was used to reproduce certain functional characteristics observed in seven healthy volunteers, such as the distribution (amplitude and phase shift) of arterial, venous, and CSF flows. The results show a good agreement between measured and simulated intracranial CSF and blood flows.