Competing correlated states around the zero-field Wigner crystallization transition of electrons in two dimensions.

The competition between kinetic energy and Coulomb interactions in electronic systems leads to complex many-body ground states with competing orders. Here we present zinc oxide-based two-dimensional electron systems as a high-mobility system to study the low-temperature phases of strongly interacting electrons. An analysis of the electronic transport provides evidence for competing correlated metallic and insulating states with varying degrees of spin polarization. Some features bear quantitative resemblance to quantum Monte Carlo simulation results, including the transition point from the paramagnetic Fermi liquid to Wigner crystal and the absence of a Stoner transition. At very low temperatures, we resolve a non-monotonic spin polarizability of electrons across the phase transition, pointing towards a low spin phase of electrons, and a two-order-of-magnitude positive magnetoresistance that is challenging to understand within traditional metallic transport paradigms. This work establishes zinc oxide as a platform for studying strongly correlated electrons in two dimensions.

Staphylococcus aureus in Substrates for Black Soldier Fly Larvae (Hermetia illucens) and Its Dynamics during Rearing.

Black soldier fly larvae (BSFL; Hermetia illucens) are promising insects for the conversion of organic waste streams into valuable biomolecules. Such waste streams can contain foodborne pathogens. To assess this risk factor, this study evaluated the presence of Staphylococcus aureus in waste streams as a substrate ingredient for BSFL production as well as in the rearing process. First, the general microbiological quality and the occurrence of S. aureus were investigated for different waste streams. Staphylococcus aureus was abundantly present. Control of pH and water activity should avoid pathogens, which cannot grow in single-substrate ingredients, redeveloping when mixing streams for optimal substrate conditions for BSFL production. Next, it was investigated whether S. aureus present in the substrate was ingested and/or eradicated by BSFL. In inoculation trials, with S. aureus added to chicken feed as the substrate at 3 or 7 log CFU/g, the larvae showed a reducing effect on S. aureus. After 6 days, S. aureus counts were below the detection limit (2.0 log CFU/g) in all larvae samples and decreased in the substrate to <2.0 and <3.1 log CFU/g for inoculation levels of 3 and 7 log CFU/g, respectively. While this is promising, it is still recommended to monitor and control this pathogen in BSFL rearing. Intriguingly, screening of antimicrobial activity of dominant microorganisms associated with BSFL showed a clear activity of Trichosporon isolates against S. aureus. Future research should explore whether Trichosporon, which is frequently observed in BSFL, plays a role in controlling specific microorganisms, such as S. aureus. IMPORTANCE Given the increasing need for (more sustainable) methods to upcycle organic waste streams, the interest to rear insects, like black soldier fly larvae (BSFL), on such streams is increasing. This study reveals that S. aureus is abundantly present in such waste streams, which might be a point of attention for insect producers. At the same time, it reveals that when S. aureus was inoculated in chicken feed as the substrate, it was not detected in the larvae and was reduced in the substrate after 6 days. Future inoculation trials should investigate whether this reduction is substrate dependent or not. Toward the future, the role of the BSFL microbiota in controlling intestinal bacterial community homeostasis should be explored, because one of the dominant microorganisms associated with BSFL, Trichosporon spp., showed clear activity against S. aureus.

Dynamics of Salmonella inoculated during rearing of black soldier fly larvae (Hermetia illucens).

The black soldier fly is currently the most produced edible insect on industrial scale, with its larval stage being processed into animal feed as the main application. As this insect species enters the feed and food chain, good hygiene and monitoring practices are needed to avoid the entrance of foodborne pathogens via the larvae. However, insufficient data on the risk of such introductions via industrial larvae production are available. To address this gap, a range of rearing trials were conducted in which the substrate, chicken feed, was inoculated with different levels of Salmonella and in which total viable counts and Salmonella counts were determined during the following days. The outgrowth of Salmonella was slower in those experiments with a lower initial contamination level than in experiments with a higher level. No significant reducing effect originating from the larvae on the substrate Salmonella counts was observed, in contrast to previous studies using other substrates. Our study also revealed that airborne transmission of Salmonella is possible under rearing conditions corresponding to those applied at industrial production sites. Based on our results, we recommend insect producers to use substrate ingredients free of Salmonella, and not to count on the antimicrobial activities that BSFL may exert in some situations towards food pathogens. More inoculation studies using other Salmonella serotypes, other zoonotic bacteria, other substrates, larvae of other ages and including variations on rearing protocols are needed in order to obtain a general view on the dynamics of food pathogens in this insect species and to support comprehensive risk assessments.

A uniaxial force and stiffness model of the vagina during laparoscopic sacrocolpopexy.

BACKGROUND: Laparoscopic sacrocolpopexy is the preferred procedure for restoring vaginal vault prolapse. An assistant uses a vaginal manipulator to position and tension the vault such that the surgeon can dissect the bladder, rectum and vault to eventually suture a synthetic mesh used to suspend the vagina to the longitudinal anterior vertebral ligament. Vaginal vault manipulation requires application of high forces for long periods of time. METHODS: This work quantifies the task by measuring and analyzing the interaction forces and the workspace during vaginal vault manipulation. From the measurements we developed a uniaxial model, expressing the increase in interaction force and stiffness of the vagina. By adapting the model parameters, the difference in interaction force and stiffness between moderate and severe prolapse is predicted. FINDINGS: For moderate prolapse the average interaction force and stiffness start at 2.56 N and 0.11 N mm-1 in the tensionfree state, and go up to 20.14 N and 0.53 N mm-1 after complete insertion of the instrument. For severe degrees of prolapse, tissue interaction is much lower starting at 1.68 N and 0.06 N mm-1 while staying limited to 12.20 N and 0.30 N mm-1 at full extension. INTERPRETATION: Population data shows that the stage of prolapse and total vaginal length increase with age and parity. The interaction force and stiffness of the vagina are correlated with this degree of prolapse. By adapting the model parameters a good estimation of the tissue interaction is found for patients with mild and severe prolapse.

Acoustoelectric Study of Microwave-Induced Current Domains.

Surface acoustic waves (SAW) have been utilized to investigate the properties of a two-dimensional electron system subjected to a perpendicular magnetic field and monochromatic microwave radiation in the regime where the so-called microwave-induced zero-resistance states form. Contrary to conventional magnetotransport in Hall bar and van der Pauw geometries, the collimated SAW beam probes only the bulk of the electronic system exposed to this wave. Clear signatures appear in the SAW propagation velocity, corroborating that neither contacts nor sample edges are a root source for their emergence. By virtue of the directional nature of this probing method and with the assistance of theoretical modeling, we were able to demonstrate that the SAW response depends on the angle between its propagation vector and the orientation of domains that spontaneously form when zero-resistance is observed in transport. This confirms in unprecedented manner the formation of an inhomogeneous phase under these nonequilibrium conditions.

Enhanced intrinsic photovoltaic effect in tungsten disulfide nanotubes.

The photovoltaic effect in traditional p-n junctions-where a p-type material (with an excess of holes) abuts an n-type material (with an excess of electrons)-involves the light-induced creation of electron-hole pairs and their subsequent separation, generating a current. This photovoltaic effect is particularly important for environmentally benign energy harvesting, and its efficiency has been increased dramatically, almost reaching the theoretical limit1. Further progress is anticipated by making use of the bulk photovoltaic effect (BPVE)2, which does not require a junction and occurs only in crystals with broken inversion symmetry3. However, the practical implementation of the BPVE is hampered by its low efficiency in existing materials4-10. Semiconductors with reduced dimensionality2 or a smaller bandgap4,5 have been suggested to be more efficient. Transition-metal dichalcogenides (TMDs) are exemplary small-bandgap, two-dimensional semiconductors11,12 in which various effects have been observed by breaking the inversion symmetry inherent in their bulk crystals13-15, but the BPVE has not been investigated. Here we report the discovery of the BPVE in devices based on tungsten disulfide, a member of the TMD family. We find that systematically reducing the crystal symmetry beyond mere broken inversion symmetry-moving from a two-dimensional monolayer to a nanotube with polar properties-greatly enhances the BPVE. The photocurrent density thus generated is orders of magnitude larger than that of other BPVE materials. Our findings highlight not only the potential of TMD-based nanomaterials, but also more generally the importance of crystal symmetry reduction in enhancing the efficiency of converting solar to electric power.

Assessing the Microbiota of Black Soldier Fly Larvae (Hermetia illucens) Reared on Organic Waste Streams on Four Different Locations at Laboratory and Large Scale.

This study aimed to gain insight into the microbial quality, safety and bacterial community composition of black soldier fly larvae (Hermetia illucens) reared at different facilities on a variety of organic waste streams. For seven rearing cycles, both on laboratory-scale and in large-scale facilities at several locations, the microbiota of the larvae was studied. Also samples of the substrate used and the residue (= leftover substrate after rearing, existing of non-consumed substrate, exuviae and faeces) were investigated. Depending on the sample, it was subjected to plate counting, Illumina Miseq sequencing and/or detection of specific food pathogens. The results revealed that the substrates applied at the various locations differed substantially in microbial numbers as well as in the bacterial community composition. Furthermore, little similarity was observed between the microbiota of the substrate and that of the larvae reared on that substrate. Despite substantial differences between the microbiota of larvae reared at several locations, 48 species-level operational taxonomic units (OTUs) were shared by all larvae, among which most belonged to the phyla Firmicutes and Proteobacteria. Although the substrate is assumed to be an important source of bacteria, our results suggest that a variety of supposedly interacting factors-both abiotic and biotic-are likely to affect the microbiota in the larvae. In some larvae and/or residue samples, potential foodborne pathogens such as Salmonella and Bacillus cereus were detected, emphasising that decontamination technologies are required when the larvae are used in feed, just as for other feed ingredients, or eventually in food.

Current Flow in the Bubble and Stripe Phases.

The spontaneous ordering of spins and charges in geometric patterns is currently under scrutiny in a number of different material systems. A topic of particular interest is the interaction of such ordered phases with itinerant electrons driven by an externally imposed current. It not only provides important information on the charge ordering itself but potentially also allows manipulating the shape and symmetry of the underlying pattern if current flow is strong enough. Unfortunately, conventional transport methods probing the macroscopic resistance suffer from the fact that the voltage drop along the sample edges provides only indirect information on the bulk properties because a complex current distribution is elicited by the inhomogeneous ground state. Here, we promote the use of surface acoustic waves to study these broken-symmetry phases and specifically address the bubble and stripe phases emerging in high-quality two-dimensional electron systems in GaAs/AlGaAs heterostructures as prototypical examples. When driving a unidirectional current, we find a surprising discrepancy between the sound propagation probing the bulk of the sample and the voltage drop along the sample edges. Our results prove that the current-induced modifications observed in resistive transport measurements are in fact a local phenomenon only, leaving the majority of the sample unaltered. More generally, our findings shed new light on the extent to which these ordered electron phases are impacted by an external current and underline the intrinsic advantages of acoustic measurements for the study of such inhomogeneous phases.

Tigecycline-induced inhibition of mitochondrial DNA translation may cause lethal mitochondrial dysfunction in humans.

BACKGROUND: A 65-year-old patient developed an unexplained and ultimately lethal metabolic acidosis under prolonged treatment with tigecycline. Tigecycline is known to have a selective inhibitory effect on eukaryotic mitochondrial translation. The underlying molecular mechanisms of the metabolic acidosis in this patient were explored. METHODS: Oxidative phosphorylation system (OXPHOS) analysis, blue native polyacrylamide gel electrophoresis followed by in-gel activity staining in mitochondria, molecular analysis of mitochondrial DNA (mtDNA) for genomic rearrangements and sequencing of the rRNA genes was performed on the subject's skeletal muscle. RESULTS: OXPHOS analysis revealed a combined deficiency of the complexes I, III, IV and V, with a preserved function of complex II (encoded by nuclear DNA), thus demonstrating a defective mtDNA translation. There were no known underlying mitochondrial genetic defects. The patient had a (m.1391T>A) variant within the 12SrRNA gene in heteroplasmy (50-60%). CONCLUSIONS: This patient developed an ultimately lethal mitochondrial toxicity while receiving prolonged treatment with tigecycline, which was caused by a defective translation of the mtDNA. Tigecycline is known to suppress eukaryotic mitochondrial DNA translation, but until now this effect has been considered to be clinically insignificant. The observations in this patient suggest a clinically significant mitochondrial toxicity of tigecycline in this patient, and warrant further investigation.

Microwave-Induced Oscillations in Magnetocapacitance: Direct Evidence for Nonequilibrium Occupation of Electronic States.

In a two-dimensional electron system, microwave radiation may induce giant resistance oscillations. Their origin has been debated controversially and numerous mechanisms based on very different physical phenomena have been invoked. However, none of them have been unambiguously experimentally identified, since they produce similar effects in transport studies. The capacitance of a two-subband system is sensitive to a redistribution of electrons over energy states, since it entails a shift of the electron charge perpendicular to the plane. In such a system, microwave-induced magnetocapacitance oscillations have been observed. They can only be accounted for by an electron distribution function oscillating with energy due to Landau quantization, one of the quantum mechanisms proposed for the resistance oscillations.

[Non-identified antinuclear antibodies in systemic sclerosis]. / Facteurs anti-nucléaires " non-identifiés " dans la sclérodermie systémique.

INTRODUCTION: Systemic sclerosis is a rare auto immune disease characterized by a local or diffuse skin condition and a variable visceral impairment. Anti nuclear antibodies (ANA) can be found in 95 % of patients. The most frequent are the anti topoisomerase 1 or anti Scl 70 and the anti-centromeres. Other antibodies have been reported but they are not conventionally sought in clinical practice. They are referred to as " non identified " ANA. OBJECTIVE: To seek the " non identified " antibodies in patients with scleroderma at Erasme Hospital, to assess their prevalence in this cohort and to correlate their presence with the clinical characteristics. METHODS: 89 patients out of the cohort of Erasme hospital patients with scleroderma have been looked at. Their clinical and biological data have been identified and a detection of antibodies have been performed by first an immonudot technique and second an EliA technique. RESULTS: 17 out of the 89 patients of our cohort had " non identified " ANA. Among them, antibodies in 11 patients have been identified by the immunodot, among which 7 anti-PmScl 75 and/or 100,3 RNA polymerase III and 1 antifibrillarin. The EliA technique identif ied antibodies in 10 patients among which 5 anti- PmScl, 2 anti RNA polymerase, 2 anti-fibrillarin and 1 anti-centromere. CONCLUSION: Auto antibodies other than the antitopoisomerase and anti-centromere have been found in patients with scleroderma in our cohort. Certain links exist between the presence of a given antibody and clinical features. We still have to define whether there exist other auto antibodies of which we still are unaware since in some patient no antibodies were detected.

INTRODUCTION: La sclérodermie systémique est une maladie auto-immune rare caractérisée par une atteinte cutanée locale ou diffuse ainsi qu'une atteinte viscérale variable. On retrouve des facteurs anti-nucléaires (FAN) chez environ 95 % des malades, dont les plus fréquents sont les anti-topoisomérase I (ou anti-Scl 70) et les anticentromères. D'autres auto-anticorps ont été décrits mais ceux-ci ne sont pas classiquement recherchés en pratique clinique, on les dénomme alors " FAN non identifiés ". OBJECTIF: Rechercher les anticorps " non identifiés " chez les patients sclérodermiques de l'hôpital Erasme, établir leur prévalence dans cette cohorte et corréler leur présence avec les caractéristiques cliniques. METHODES: Quatre-vingt-neuf patients issus de la cohorte des patients sclérodermiques de l'hôpital Erasme ont été étudiés. Leurs données cliniques et biologiques ont été relevées, puis une détection d'anticorps a été effectuée d'une part par une technique d'immunodot (topoisomérase I, centromères, ARN polymérase III, fibrillarine, Pm/Scl 75 et 100, PDGFR, NOR 90, Ku et Ro 52) et d'autre part par une technique EliA (topoisomérase I, centromères, ARN polymérase III, fibrillarine et PmScl). RESULTATS: Dix-sept des 89 patients de notre cohorte avaient des FAN " non identifiés ". Parmi ceux-ci, l'immunodot a identifié des anticorps chez 11 patients dont 7 anti-PmScl 75 et/ou 100, 3 anti-ARN pol III et 1 anti-fibrillarine. La technique EliA a permis d'identifier des anticorps chez 10 patients dont 5 anti-PmScl, 2 anti-ARN pol III, 2 anti-fibrillarine et 1 anti-centromère. CONCLUSION: Des auto-anticorps autres que les anti-topoisomérase I et anti-centromères ont été retrouvés chez les patients sclérodermiques de notre cohorte. Il existe certains liens entre la présence d'un anticorps donné et la clinique associée. Il reste à définir s'il existe d'autres auto-anticorps qui ne sont pas encore connus puisque chez certains patients, aucun anticorps n'a été mis en évidence.

Mitochondrial Neurogastrointestinal Encephalopathy: Clinical, Biochemical and Molecular Study in Three Egyptian Patients.

Background: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare autosomal recessive disorder. The disease is caused by mutations in the thymidine phosphorylase gene. This article reports the clinical, biochemical and molecular findings in three Egyptian patients with Mitochondrial Neurogastrointestinal Encephalopathy sundrome from two different pedigrees. Subjects and Methods: The three patients were subjected to thorough neurologic examination. Brain Magtnetic Resonance Imaging. Histochemical and biochemical assay of the mitochondrial respiratory chain complexes in muscle homogenate was performed (1/3). Thymidine Phosphorylase enzyme activity was performed in 2/3 patients and Thymidine Phosphorylase gene sequencing was done (2/3) to confirm the diagnosis. Results: All patients presented with symptoms of severe gastrointestinal dysmotility with progressive cachexia, neuropathy, sensory neural hearing loss, asymptomatic leukoencephalopathy. Histochemical analysis of themuscle biopsy revealed deficient cytochrome C oxidase and mitochrondrial respiratory chain enzyme assay revealed isolated complex 1 deficiency (1/3). Thymidine Phosphorylase enzyme activity revealed complete absence of enzyme activity in 2/3 patients. Direct sequencing of Thymidine Phosphorylase gene revealed c.3371 A>C homozygous mutation. Molecular screening of both families revealed heterozygous mutation in both parents and 4 siblings. Conclusions: Mitochondrial Neurogastrointestinal Encephalopathy syndrome is a rare mitochondrial disorder with an important diagnostic delay. In case of pathogenic mutations in Thymidine Phosphorylase gene in the family, carrier testing and prenatal diagmosis of at risk members is recommended for early detection. The possibility of new therapeutic options makes it necessary to diagnose the disease in an early state.

Random flips of electric field in microwave-induced states with spontaneously broken symmetry.

In a two-dimensional electron system subject to microwaves and a magnetic field, photovoltages emerge. They can be separated into two components originating from built-in electric fields and electric field domains arising from spontaneous symmetry breaking. The latter occurs in the zero resistance regime only and manifests itself in pulsed behavior, synchronous across the sample. The pulses show sign reversal. This implies a flip of the field in each domain, consistent with the existence of two equally probable electric field domain configurations due to the spontaneous symmetry breaking.

Genomic standards consortium projects.

The Genomic Standards Consortium (GSC) is an open-membership community that was founded in 2005 to work towards the development, implementation and harmonization of standards in the field of genomics. Starting with the defined task of establishing a minimal set of descriptions the GSC has evolved into an active standards-setting body that currently has 18 ongoing projects, with additional projects regularly proposed from within and outside the GSC. Here we describe our recently enacted policy for proposing new activities that are intended to be taken on by the GSC, along with the template for proposing such new activities.

Quantized ν = 5/2 state in a two-subband quantum hall system.

The evolution of the fractional quantum Hall state at filling 5/2 is studied in density tunable two-dimensional electron systems formed in wide wells in which it is possible to induce a transition from single- to two-subband occupancy. In 80 and 60 nm wells, the quantum Hall state at 5/2 filling of the lowest subband is observed even when the second subband is occupied. In a 50 nm well, the 5/2 state vanishes upon second subband population. We attribute this distinct behavior to the width dependence of the capacitive energy for intersubband charge transfer and of the overlap of the subband probability densities.

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome.

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system.

A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.

Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype-phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early-onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron-sulfur clusters in NDUFV1.

Collective modes and the periodicity of quantum Hall stripes.

We investigate the quantum Hall stripe phase at filling factor 9/2 at the microscopic level by probing the dispersion of its collective modes with the help of surface acoustic waves with wavelengths down to 60 nm. The dispersion is strongly anisotropic. It is highly dispersive and exhibits a roton minimum for wave vectors aligned along the easy transport direction. In the perpendicular direction, however, the dispersion is featureless, although not flat as predicted by theory. Oscillatory behavior in the absorption intensity of the collective mode with a wave vector perpendicular to the stripes is attributed to a commensurability effect. It allows us to extract the periodicity of the quantum Hall stripes.

Are the reference values of B cell subpopulations used in adults for classification of common variable immunodeficiencies appropriate for children?

Detailed phenotypic characterization of B cell subpopulations is of utmost importance for the diagnosis and management of humoral immunodeficiencies, as they are used for classification of common variable immunodeficiencies. Since age-specific reference values remain scarce in the literature, we analysed by flow cytometry the proportions and absolute values of total, memory, switched memory and CD21(-/low) B cells in blood samples from 168 healthy children (1 day to 18 years) with special attention to the different subpopulations of CD21(low) B cells. The percentages of total memory B cells and their subsets significantly increased up to 5-10 years. In contrast, the percentages of immature CD21(-) B cells and of immature transitional CD21(low)CD38(hi) B cells decreased progressively with age, whereas the percentage of CD21(low) CD38(low) B cells remained stable during childhood. Our data stress the importance of age-specific reference values for the correct interpretation of B cell subsets in children as a diagnostic tool in immunodeficiencies.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

BACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.