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Metabolic disorders are often associated with liver steatosis and increased plasma cholesterol levels. However, the link between excessive lipid accumulation and impairments in cholesterol metabolism remains uninvestigated in the liver. Short term of high‐fat diet (HFD) was previously shown to promote excessive lipid accumulation prior to the development of metabolic disorders. The present study intended to characterize how increases in liver fat alter the expression of several key regulators of hepatic cholesterol metabolism in response to a short‐term HFD. Wistar rats were randomly submitted either to HFD (n = 8) or a regular chow diet (n = 8) for 14 days. Increases in triglycerides were highly significant (P < 0.01) in the liver but marginal in the plasma of HFD rats. In contrast, the HFD resulted in higher (P < 0.01) cholesterol levels in plasma but not in liver samples. Gene expression of key markers involved in cholesterol uptake (LDL particles) including low‐density lipoprotein receptor‐related protein‐1 (LRP‐1) and protein convertase subtilisin/kexin type 9 (PCSK9) along with ATP‐binding cassette, superfamily G, member 5 (ABCG5) involved in cholesterol exportation via bile ducts was found to be higher (P < 0.05) in response to the HFD. In contrast, expression of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR), involved in cholesterol synthesis, was downregulated in the liver. The data support the concept that excessive accumulation of lipids promptly alters the expression of key genes regulating cholesterol metabolism in the liver. On a clinical point of view, this indicates that increases in plasma cholesterol occur after a short‐term HFD. [ABSTRACT FROM AUTHOR]

We study a generalized time‐harmonic transport equation, which appears in the Goldstein equations and allows us to model the acoustic radiation in a flow. We investigate the well‐posedness of this transport problem. The result will be established under the assumption of a Ω‐filling flow, which, in 2D, is simply equivalent to a flow that does not vanish. The approach relies on the method of characteristics, which leads to the resolution of the transport equation along the streamlines, and on general results of functional analysis. The theoretical results are illustrated with numerical results obtained with a Streamline Upwind Petrov‐Galerkin finite element scheme. [ABSTRACT FROM AUTHOR]

The contact zone between two major allochthonous lithotectonic units in the French Massif Central (FMC) is characterized by the presence of corundum-bearing amphibolites associated with serpentinites, flaser-gabbros, eclogites and granulites. These unusual amphibolites are best preserved in the Western FMC, where they are found within the lower oceanic crust of the Limousin ophiolite. Mineralogical observations and thermodynamic modelling of the spinel–corundum–sapphirine–kyanite amphibolites in the CMASH system show that they were formed at peak P–T conditions around 800 °C/10 kbar in response to near isothermal burial followed by a retrogressive anticlockwise path. Metamorphic reactions are controlled both by modification of P–T conditions and by local chemical changes linked to fluid infiltration. Pargasite growth has been enhanced by infiltration of Ca- and Al-rich fluids whereas kyanite- and sapphirine-forming reactions are partly controlled by local inputs of MgO–SiO2 components, most probably during infiltration metasomatism. By analogy with worldwide ophiolites (Oman, Tethyan, Appalachian) and published numerical models, subduction of a still-hot oceanic ridge is proposed to form these Al-rich amphibolites from plagioclase-rich troctolites. The trace-element composition of high-Ti, fine-grained amphibolites (former fine-grained Fe–Ti gabbros) adjacent to the corundum-bearing ones, further indicates that the oceanic crust was initially created at a mid-ocean ridge (rather than within a back-arc basin), followed by the emplacement of supra-subduction zone-type magmas, probably due to intraoceanic subduction close to the ridge. [ABSTRACT FROM AUTHOR]

Aim: To determine whether endurance training can counterbalance the negative effects of hypoxia on mitochondrial phosphorylation and expression of the long chain mitochondrial fatty acid transporter muscle carnitine palmitoyl transferase 1 (mCPT-1). Methods: Male Wistar rats were exposed either to hypobaric hypoxia (at a simulated altitude of ≈4000 m, PIO2 ≈ 90 mmHg) or to normoxia (sea level) for 5 weeks. In each environment, rats were randomly assigned to two groups. The trained group went through a 5-week endurance training programme. The control group remained sedentary for the same time period. Muscle fatty acid oxidation capacity was evaluated after the 5-week period on isolated mitochondria prepared from quadriceps muscles with the use of palmitoylcarnitine or pamitoylCoA + carnitine. Results: Chronic hypoxia decreased basal ( V0, −31% with pamitoylCoA + carnitine and −21% with palmitoylcarnitine, P < 0.05) and maximal ( Vmax, −31% with pamitoylCoA + carnitine, P < 0.05) respiration rates, hydroxyacylCoA dehydrogenase activity (−48%, P < 0.05), mCPT-1 activity index (−34%, P < 0.05) and mCPT-1 protein content (−34%, P < 0.05). Five weeks of endurance training in hypoxia brought V0, mCPT-1 activity index and mCPT-1 protein content values back to sedentary normoxic levels. Moreover, in the group trained in hypoxia, Vmax reached a higher level than in the group that maintained a sedentary lifestyle in normoxia (24.2 nmol O2· min−1 · mg−1 for hypoxic training vs. 19.9 nmol O2 · min−1 · mg−1 for normoxic sedentarity, P < 0.05). Conclusion: Endurance training can attenuate chronic hypoxia-induced impairments in mitochondrial fatty acid oxidation. This training effect seems mostly mediated by mCPT-1 activity rather than by mCPT-1 content. [ABSTRACT FROM AUTHOR]

Cardiocondyla elegans is a Mediterranean ant that nests on river banks. It rears only wingless (ergatoid) males that live peacefully in the same nest as opposed to other species of the same genus, which have both peaceful, winged and mutually aggressive ‘ergatoid’ males. Using microsatellite analysis, we investigated the genetic structure of 21 colonies from three different locations as well as the parentage of sexuals of two colonies of C. elegans. We show that C. elegans is strictly monogynous, and that its nests can contain foreign sexuals. The presence of alien sexuals inside ant nests is described for the first time and probably counteracts inbreeding resulting from matings between siblings. In the laboratory, aggression tests showed that workers only allow alien males to enter their nests, while all winged female sexuals attempting to enter were attacked. Nevertheless, the presence of alien female sexuals in nests in the field seems to result from active carrying behaviour by workers during the reproductive period. [ABSTRACT FROM AUTHOR]

Background The aim of the study was to characterize lipid oxidation at exercise in adults with growth hormone deficiency (GHD) and to evaluate the effect of 6 and 12 months of GH replacement therapy on substrate carbohydrate (CHO) and lipid utilization at exercise. Patients and measurements Twenty-five patients with GHD and 40 matched controls participated in the study. Ten of the 25 GH-deficient patients were treated with recombinant GH for 12 months. Anthropometric measurements and exercise calorimetry were performed before and after treatment. Maximal fat oxidation and the crossover point [that is the percentage of the theoretical maximal power (Wmax th) where CHO become the predominant fuel used for oxidation] were determined. Results and conclusion The GH-deficient patients exhibited a highly significant shift in the balance of substrate oxidation during exercise, towards a decrease in fat oxidation, and a shift towards lower intensities of the crossover (52 ± 5·5% vs. 72·6 ± 6·6% of Wmax th, P < 0·03) and maximal fat oxidation (131·04 ± 14 vs. 234·4 ± 30·1 mg/min, P < 0·03) in the GHD and control groups, respectively. However, GH treatment at 6 and 12 months partially reversed this defect, resulting in an increase (+83%, P < 0·001) in the maximal ability to oxidize fat during exercise. These findings are consistent with the hypothesis that a lack of GH reduces the ability to oxidize lipids during exercise and that GH treatment restores this muscular metabolic property. [ABSTRACT FROM AUTHOR]

The Limousin ophiolite is located at the suture zone between two major thrust sheets in the western French Massif Central. This ophiolitic section comprises mantle-harzburgite, mantle-dunite, wehrlites, troctolites and layered gabbros. It has recorded a static metamorphic event transforming the gabbros into undeformed amphibolites and the magmatic ultramafites into serpentinites and/or pargasite-bearing chloritites. With various thermobarometric methods, it is possible to show that the different varieties of amphibole have registered low- P ( c. 0.2 GPa) conditions with temperature ranging from high- T, late-magmatic conditions to greenschist–zeolite metamorphic facies. The abundance of undeformed metamorphic rocks (which is typical of the lower oceanic crust), the occurrence of Ca–Al (–Mg) metasomatism illustrated by the growth of Ca–Al silicates in veins or replacing the primary magmatic minerals, the P– T conditions of the metamorphism and the numerous similarities with oceanic crustal rocks from Ocean Drilling Program and worldwide ophiolites are the main arguments for an ocean-floor hydrothermal metamorphism in the vicinity of a palaeo-ridge. Among the West-European Variscan ophiolites, the Limousin ophiolites constitute an extremely rare occurrence that has not been involved in any HP (subduction-related) or MP (orogenic) metamorphism as observed in other ophiolite occurrences (i.e. France, Spain and Germany). [ABSTRACT FROM AUTHOR]

At Iranian longitude, the Arabian plate is moving northward relative to Eurasia (∼20 mm yr−1 according to GPS). To the east, this relative motion is accommodated by northward subduction under the E-W Makran emerged accretionary prism. To the west, it is accommodated partly by the Zagros fold-and-thrust belt and partly by the Alborz/Kopet Dagh deforming zones further north. This work investigates the NNW striking transition zone that connects Zagros and Makran: the Minab-Zendan fault system. Satellite images, and structural and geomorphic field observations show a distributed deformation pattern covering a wide domain. Five north to NW trending major faults were identified. They exhibit evidence for late Quaternary reverse right-lateral slip, and correspond to two distinct fault systems: the western one transferring the Zagros deformation to the Makran prism, and the eastern one northward transferring the deformation to the Alborz/Kopet Dagh. Tectonic study and fault slip vector analyses indicate that two distinct tectonic regimes have occurred successively since the Miocene within a consistent regional NE trending compression: (1) an upper Miocene to Pliocene tectonic regime characterized by partitioned deformation, between reverse faulting and en echelon folding; (2) a NE trending σ1 axis transpressional regime homogeneously affecting the region since upper Pliocene. The change is contemporaneous with major tectonic reorganization regionally recorded. Therefore this study provides evidence for active deformation that is not localized, but distributed across a wide zone. It accommodates the convergence and transfers it from collision to subduction by transpressional tectonics without any partitioning process in the present-day period. [ABSTRACT FROM AUTHOR]

Respiratory failure in the premature neonate is frequently complicated by pulmonary hypertension. When conventional therapies including administration of exogenous surfactant, conventional mechanical ventilation or high-frequency oscillatory ventilation using an appropriate high-volume strategy have failed, one should assess the pulmonary circulation status with colour-coded Doppler echocardiography. There is now considerable evidence that the regulation of foetal and postnatal pulmonary circulation occurs via nitric oxide (NO), and that persistent pulmonary hypertension of the neonate may be related to a relative deficiency in NO release. Low-dose (10-20 ppm), short-duration (1-2 d) inhaled NO has generally been shown to improve the oxygenation and relieve pulmonary hypertension in premature neonates with severely hypoxaemic respiratory failure. Whether this therapy (eventually prolonged >1-3 wk?) would improve survival and lessen morbidity (e.g. intracranial haemorrhage and chronic lung disease) remains to be proven by appropriately designed controlled trials. Until these issues can be clarified, NO therapy for premature neonates should be still considered as an experimental drug, and its use restricted to clinical studies. [ABSTRACT FROM AUTHOR]

Summary Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise-induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphazise the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects. [ABSTRACT FROM AUTHOR]

Presents information on a study which investigated the effect of pre-storage exposure to shortwave ultra-violet (UV) light on the decay and quality of fresh strawberries. Materials and methods; Results and discussion; Evaluation of fungal decay; Effect of UV on fungal decay; Conclusions.

A null β-casein allele (CSN2O) was investigated in Creole and Pyrenean goats producing milk devoid of β-casein (CSN2). Northern blot analyses of total mammary RNA showed much lower amounts of CSN2 transcripts that were similar in size to the wild-type counterpart. The amount of CSN2O mRNA was roughly 5% of the amount of mRNA obtained at the same age and stage of lactation from CSN2A/A goats. Comparative sequence analyses of full-length CSN2O and CSN2A cDNAs showed that both alleles were of similar size, but allele CSN2O had a one-nucleotide deletion in the 5′ end of exon 7, which introduces a premature stop codon. The open reading frame of allele CSN2O encodes a shortened polypeptide of 72 amino acids, compared to 223 amino acids for caprine preβ-casein A. Comparative analyses of RT-PCR products suggested that alleles CSN2O and CSN2A might also differ in the amount and relative ratio of minor deleted CSN2 transcripts. The lower amount of CSN2O mRNA was associated with the occurrence of the premature stop codon which may mediate a rapid decay of CSN2O mRNA and promote skipping of nucleotide stretches containing premature nonsense triplets. [ABSTRACT FROM AUTHOR]

New paleomagnetic data are reported from the islands of Skyros and Lesbos in Central Aegea and the Izmir-Foça region in Western Anatolia. Together with previous results obtained in Northwestern Greece and with results from Northern Aegea reported by others authors, these data suggest that the Lower Miocene arc was almost rectilinear, trending E-W and that the curvature was acquired by opposed rotational deformations at each termination. Moreover, the observed inclinations, which are shallower than those expected on the basis of a geocentered dipole field, suggest a large northward drift since Middle Miocene. [ABSTRACT FROM AUTHOR]

Three massifs in the Xigaze area (Southern Tibet, China), have been preserved from the intense deformation observed everywhere else in the Yarlung Zangbo Suture Zone. These massifs have similar lithologies and display a remarkable homogeneity in the attitude of most magmatic and tectonic structures such as lava flow planes, dolerite dikes and sills, and foliation planes in peridotites. This indicates that these ophiolites are only slightly dismembered, inasmuch as they locally display complete sequences from pillow lavas at the top to fresh Cr-diopside-bearing harzburgites at the base. Gabbroic rocks are rare and are present as screens between dolerite intrusives or in small-sized pockets at the limit between mafic and ultramafic rocks. One of the most important feature of this ophiolite is the occurrence of dolerite sills and dikes throughout the whole sequence indicating that this ophiolite results from to two successive magmatic events with (1) creation of the crustal part of the oceanic lithosphere with deposition of minor cumulates in small magma chambers over mantle residual rocks and (2) intrusion of dolerite sills and dikes throughout the whole sequence. [ABSTRACT FROM AUTHOR]

The mass spectra of two series of 2-substituted-2,3-dihydro-4 H-pyrans (six ethers and six carbonyl derivatives) showed a marked dependence upon the nature of the substituent. α-Cleavage (substituent loss) was the only primary decomposition observed in the carbonyl series, while 'retro Diels-Alder' reactions competed with α-cleavage in the ether series. An unambiguous interpretation of this difference in behaviour, based on the consequence of charge localization and thermochemical data, is proposed. [ABSTRACT FROM AUTHOR]

Biotic (β-glucan, fructosan and polygalacturonic acid fragments) and abiotic agents (ultraviolet- C radiation, gamma radiation and heat) were screened for their potential to elicit the accumulation of the phytoalexm 6-methoxymellein in carrot slices. Ultraviolet radiation was the only elicitor found effective, with an optimum dose of 2.20 X 103 erg cm"2. At 20 °C, the maximum level was reached in 72 hours and thereafter degradation was apparent. At lower temperatures (1° or 4 °C), 6-methoxymellein accumulation was slower but reached higher levels which remained stable for up to 35 days after induction. Ultraviolet-treated slices which were stored at 1° or 4 °C for two weeks to allow 6- methoxymellem accumulation were significantly more resistant to infection when challenged with Botrytis cinerea or Sclerotinia sclerotiorum. Slices inoculated immediately after ultraviolet treatment did not show any resistance. The data showed that concentrations of 6-methoxymellein above 30 ^g g"1 of tissue were inhibitory to B. cinerea, with maximum inhibition observed around 60 jug g"1. Thus ultraviolet treatment could have potential to enhance the resistance of carrots to storage pathogens. [ABSTRACT FROM AUTHOR]

The possibility of inducing systemic disease resistance in carrot leaves was investigated with the pathogen Cercospora carotae as the agent for both induction and challenge. The inoculation of plants with C. carotae induced resistance in newly emerged leaves challenged 23 days later. There was an optimum inoculum concentration of 3 x 104 it conidia ml for inducing resistance, the response decreasing with higher concentrations. Infection of carrot leaves by C. carotae could thus reduce susceptibility to subsequent infections by foliar pathogens tater in the growing season. However, the inoculation of leaves with C. carotae did not increase the resistance of roots after harvest when they were wounded and challenged with Botryris cinerea. [ABSTRACT FROM AUTHOR]

The article discusses a case regarding a child with abnormal ocular movements. He was born at term by non-consanguineous healthy parents. From the age of 3 months until 1 year, he showed paroxysmal episodes of torticollis associated with vomiting. He was admitted twice because of acute axial dystonia without any associated clinical sign. He showed paroxysmal episodes of conjugate upgaze frequently in the occasion of a febrile illness. He underwent neuroradiological and neurophysiological examinations including interictal video-electroencephalography (EEG) recording, brain magnetic resonance imaging (MRI), brainstem evoked potentials and ophthalmological examination.

The ubiquitin-proteasome system is known to be involved in many situations leading to skeletal muscle atrophy. However, the cellular mechanisms triggering the atrophic process initiation are still poorly understood. For short periods of rat hindlimb unloading, we assessed the specific ubiquitin targeting of sarcoplasmic or myofibrillar proteins in slow and fast rat muscle types. Adult Sprague Dawley rats were randomly assigned to three groups: control, hindlimb-unloaded for 4 days (HU4) and hindlimb-unloaded for 8 days (HU8). In fractionated extracts from soleus (SOL) and Extensor Digitorum Longus (EDL) muscles, the relative contents of free and conjugated ubiquitin were quantified by immunoblotting. Hindlimb unloading of short durations resulted in a preferential atrophy of slow-twitch fibres and bound ubiquitin levels were increased by 37 and 68% in the soleus myofibrillar fraction after respectively 4 and 8 days. The ubiquitin conjugation was shown to principally affect the high molecular weight proteins. Free and conjugated ubiquitin levels remained unchanged in sarcoplasmic fraction from SOL muscle after 8 days HU. For the fast muscle (EDL), ubiquitin contents were approximately twofold lower in control conditions, and did not significantly change during the hindlimb unloading periods considered. The postural SOL muscle was shown to contain higher constitutive sarcoplasmic ubiquitin levels than the phasic EDL. The high response to unloading of the slow twitch fibres rich SOL muscle was accompanied by a specific conjugation of its myofibrillar proteins that may participate in the initiation of skeletal muscle remodelling consequent to disuse. [ABSTRACT FROM AUTHOR]

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report on clinical, genetic and metabolic investigations in a family with optic neuropathy, non-progressive cardiomyopathy and cognitive disability. Ophthalmic investigations (slit lamp examination, funduscopy, OCT scan of the optic nerve, ERG and VEP) disclosed mild or no decreased visual acuity, but pale optic disc, loss of temporal optic fibers and decreased VEPs. Mitochondrial DNA and exome sequencing revealed a novel homozygous mutation in the nuclear MTO1 gene and the homoplasmic m.593T>G mutation in the mitochondrial MT-TF gene. Muscle biopsy analyses revealed decreased oxygraphic Vmax values for complexes I+III+IV, and severely decreased activities of the respiratory chain complexes (RCC) I, III and IV, while muscle histopathology was normal. Fibroblast analysis revealed decreased complex I and IV activity and assembly, while cybrid analysis revealed a partial complex I deficiency with normal assembly of the RCC. Thus, in patients with a moderate clinical presentation due to MTO1 mutations, the presence of an optic atrophy should be considered. The association with the mitochondrial mutation m.593T>G could act synergistically to worsen the complex I deficiency and modulate the MTO1-related disease., (© 2015 Wiley Periodicals, Inc.)

The mechanisms leading to skeletal limb muscle dysfunction in chronic obstructive pulmonary disease (COPD) have not been fully elucidated. Exhausted muscle regenerative capacity of satellite cells has been evocated, but the capacity of satellite cells to proliferate and differentiate properly remains unknown. Our objectives were to compare the characteristics of satellite cells derived from COPD patients and healthy individuals, in terms of proliferative and differentiation capacities, morphological phenotype and atrophy/hypertrophy signalling, and oxidative stress status. Therefore, we purified and cultivated satellite cells from progressively frozen vastus lateralis biopsies of eight COPD patients and eight healthy individuals. We examined proliferation parameters, differentiation capacities, myotube diameter, expression of atrophy/hypertrophy markers, oxidative stress damages, antioxidant enzyme expression and cell susceptibility to H2 O2 in cultured myoblasts and/or myotubes. Proliferation characteristics and commitment to terminal differentiation were similar in COPD patients and healthy individuals, despite impaired fusion capacities of COPD myotubes. Myotube diameter was smaller in COPD patients (P = 0.015), and was associated with a higher expression of myostatin (myoblasts: P = 0.083; myotubes: P = 0.050) and atrogin-1 (myoblasts: P = 0.050), and a decreased phospho-AKT/AKT ratio (myoblasts: P = 0.022). Protein carbonylation (myoblasts: P = 0.028; myotubes: P = 0.002) and lipid peroxidation (myotubes: P = 0.065) were higher in COPD cells, and COPD myoblasts were significantly more susceptible to oxidative stress. Thus, cultured satellite cells from COPD patients display characteristics of morphology, atrophic signalling and oxidative stress similar to those described in in vivo COPD skeletal limb muscles. We have therefore demonstrated that muscle alteration in COPD can be studied by classical in vitro cellular models., (© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent hereditary muscle disorders. It is linked to contractions of the D4Z4 repeat array in 4q35. We have characterized the double homeobox 4 (DUX4) gene in D4Z4 and its mRNA transcribed from the distal D4Z4 unit to a polyadenylation signal in the flanking pLAM region. It encodes a transcription factor expressed in FSHD but not healthy muscle cells which initiates a gene deregulation cascade causing differentiation defects, muscle atrophy and oxidative stress. PITX1 was the first identified DUX4 target and encodes a transcription factor involved in muscle atrophy. DUX4 was found expressed in only 1/1000 FSHD myoblasts. We have now shown it was induced upon differentiation and detected in about 1/200 myotube nuclei. The DUX4 and PITX1 proteins presented staining gradients in consecutive myonuclei which suggested a diffusion as known for other muscle nuclear proteins. Both protein half-lifes were regulated by the ubiquitin-proteasome pathway. In addition, we could immunodetect the DUX4 protein in FSHD muscle extracts. As a model, we propose the DUX4 gene is stochastically activated in a small number of FSHD myonuclei. The resulting mRNAs are translated in the cytoplasm around an activated nucleus and the DUX4 proteins diffuse to adjacent nuclei where they activate target genes such as PITX1. The PITX1 protein can further diffuse to additional myonuclei and expand the transcriptional deregulation cascade initiated by DUX4. Together the diffusion and the deregulation cascade would explain how a rare protein could cause the muscle defects observed in FSHD., (© 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)