Mutations in SDHD lead to autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency

BACKGROUND Defects of the mitochondrial respiratory chain complex II (succinate dehydrogenase (SDH) complex) are extremely rare. Of the four nuclear encoded proteins composing complex II, only mutations in the 70 kDa flavoprotein (SDHA) and the recently identified complex II assembly factor (SDHAF1) have been found to be causative for mitochondrial respiratory chain diseases. Mutations in the other three subunits (SDHB, SDHC, SDHD) and the second assembly factor (SDHAF2) have so far only been associated with hereditary paragangliomas and phaeochromocytomas. Recessive germline mutations in SDHB have recently been associated with complex II deficiency and leukodystrophy in one patient. METHODS AND RESULTS We present the clinical and molecular investigations of the first patient with biochemical evidence of a severe isolated complex II deficiency due to compound heterozygous SDHD gene mutations. The patient presented with early progressive encephalomyopathy due to compound heterozygous p.E69 K and p.*164Lext*3 SDHD mutations. Native polyacrylamide gel electrophoresis and western blotting demonstrated an impaired complex II assembly. Complementation of a patient cell line additionally supported the pathogenicity of the novel identified mutations in SDHD. CONCLUSIONS This report describes the first case of isolated complex II deficiency due to recessive SDHD germline mutations. We therefore recommend screening for all SDH genes in isolated complex II deficiencies. It further emphasises the importance of appropriate genetic counselling to the family with regard to SDHD mutations and their role in tumorigenesis.

Prometheus – Fuzzy Information Retrieval for Semantic Homes and Environments

This paper introduces a novel vision for further enhanced Internet of Things services. Based on a variety of data – such as location data, ontology-backed search queries, in- and outdoor conditions – the Prometheus framework is intended to support users with helpful recommendations and information preceding a search for context-aware data. Adapted from artificial intelligence concepts, Prometheus proposes user-readjusted answers on umpteen conditions. A number of potential Prometheus framework applications are illustrated. Added value and possible future studies are discussed in the conclusion.

High-resolution glacial and deglacial record of atmospheric methane by continuous-flow and laser spectrometer analysis along the NEEM ice core

The Greenland NEEM (North Greenland Eemian Ice Drilling) operation in 2010 provided the first opportunity to combine trace-gas measurements by laser spectroscopic instruments and continuous-flow analysis along a freshly drilled ice core in a field-based setting. We present the resulting atmospheric methane (CH4) record covering the time period from 107.7 to 9.5 ka b2k (thousand years before 2000 AD). Companion discrete CH4 measurements are required to transfer the laser spectroscopic data from a relative to an absolute scale. However, even on a relative scale, the high-resolution CH4 data set significantly improves our knowledge of past atmospheric methane concentration changes. New significant sub-millennial-scale features appear during interstadials and stadials, generally associated with similar changes in water isotopic ratios of the ice, a proxy for local temperature. In addition to the midpoint of Dansgaard–Oeschger (D/O) CH4 transitions usually used for cross-dating, sharp definition of the start and end of these events brings precise depth markers (with ±20 cm uncertainty) for further cross-dating with other palaeo- or ice core records, e.g. speleothems. The method also provides an estimate of CH4 rates of change. The onsets of D/O events in the methane signal show a more rapid rate of change than their endings. The rate of CH4 increase associated with the onsets of D/O events progressively declines from 1.7 to 0.6 ppbv yr−1 in the course of marine isotope stage 3. The largest observed rate of increase takes place at the onset of D/O event #21 and reaches 2.5 ppbv yr−1.

Rezidiv nach Hernienplastik: Komplikation oder natürlicher Verlauf?

Die Rezidivhäufigkeit nach Hernienplastik ist ein Qualitätsmerkmal der chirurgischen Technik. Für eine korrekte Beurteilung der Rezidivrate muss zwischen einem klinisch relevanten, klinisch irrelevanten und einem Pseudorezidiv unterschieden werden. Bei der chirurgischen Therapie von Inguinalhernien werden mit den heutigen Techniken mittels laparoskopischer oder offener Netzeinlage sehr niedrige Rezidivraten erreicht. Somit soll bei einem Rezidiv nach einer Inguinalhernienoperation von einer chirurgischen Komplikation ausgegangen werden. Im Gegensatz zur Inguinalhernie liegt die Rezidivrate bei der Operation großer Narbenhernien trotz stetiger Optimierung der Technik weiterhin über 10 %. Um das Rezidivrisiko abzuschätzen, müssen nebst der Größe und Lokalisation der Hernie technische und patientenspezifische Aspekte beurteilt werden. Je nach Risikoprofil kann das Hernienrezidiv in seltenen Fällen dem natürlichen Verlauf entsprechen. Im Allgemeinen werden Hernienrezidive als Abweichung von der Norm wahrgenommen und können von der Indikation, Wahl der Operation und der chirurgischen Technik und Taktik abhängen. Somit soll der Chirurg ein postoperatives Rezidiv in erster Linie als Komplikation und nicht als natürlichen Verlauf ansehen, mit dem Ziel die Chirurgie kontinuierlich zu verbessern.

Mutations in SLC1A4, encoding the brain serine transporter, are associated with developmental delay, microcephaly and hypomyelination

BACKGROUND L-serine plays an essential role in neuronal development and function. Although a non-essential amino acid, L-serine must be synthesised within the brain because of its poor permeability by the blood-brain barrier. Within the brain, its synthesis is confined to astrocytes, and its shuttle to neuronal cells is performed by a dedicated neutral amino acid transporter, ASCT1. METHODS AND RESULTS Using exome analysis we identified the recessive mutations, p.E256K, p.L315fs, and p.R457W, in SLC1A4, the gene encoding ASCT1, in patients with developmental delay, microcephaly and hypomyelination; seizure disorder was variably present. When expressed in a heterologous system, the mutations did not affect the protein level at the plasma membrane but abolished or markedly reduced L-serine transport for p.R457W and p.E256K mutations, respectively. Interestingly, p.E256K mutation displayed a lower L-serine and alanine affinity but the same substrate selectivity as wild-type ASCT1. CONCLUSIONS The clinical phenotype of ASCT1 deficiency is reminiscent of defects in L-serine biosynthesis. The data underscore that ASCT1 is essential in brain serine transport. The SLC1A4 p.E256K mutation has a carrier frequency of 0.7% in the Ashkenazi-Jewish population and should be added to the carrier screening panel in this community.

RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the quantitative and topographic relationship between reticular pseudodrusen (RPD) on infrared reflectance (IR) and subretinal drusenoid deposits (SDD) on en face volumetric spectral domain optical coherence tomography. METHODS: Reticular pseudodrusen were marked on IR images by a masked observer. Subretinal drusenoid deposits were visualized on en face sections of spectral domain optical coherence tomography below the external limiting membrane and identified by a semiautomated technique. Control RPD lesions were generated in a random distribution for each IR image. Binary maps of control and experimental RPD and SDD were merged and analyzed in terms of topographic localization and quantitative drusen load comparison. RESULTS: A total of 54 eyes of 41 patients diagnosed with RPD were included in this study. The average number of RPD lesions on IR images was 320 ± 44.62 compared with 127 ± 26.02 SDD lesions on en face (P < 0.001). The majority of RPD lesions did not overlap with SDD lesions and were located >30 μm away (92%). The percentage of total SDD lesions overlapping RPD was 2.91 ± 0.87% compared with 1.73 ± 0.68% overlapping control RPD lesions (P < 0.05). The percentage of total SDD lesions between 1 and 3 pixels of the nearest RPD lesion was 5.08 ± 1.40% compared with 3.33 ± 1.07% between 1 and 3 pixels of the nearest control RPD lesion (P < 0.05). CONCLUSION: This study identified significantly more RPD lesions on IR compared with SDD lesions on en face spectral domain optical coherence tomography and found that a large majority of SDD (>90% of lesions) were >30 μm away from the nearest RPD. Together, our findings indicate that RPD and SDD are two entities that are only occasionally topographically associated, suggesting that at some stage in their development, they may be pathologically related.

Pilze aus der Umgegend von Alt-Boyen

von Lehrer K. Vorwerk

Compilation of scientific results of the OASIS project

Seamounts are of great interest to science, industry and conservation because of their potential role as 'stirring rods' of the oceans, their enhanced productivity, their high local biodiversity, and the growing exploitation of their natural resources. This is accompanied by rising concern about the threats to seamount ecosystems, e.g. through over-fishing and the impact of trawling. OASIS described the functioning characteristics of seamount ecosystems. OASIS' integrated hydrographic, biogeochemical and biological information. Based on two case studies. The scientific results, condensed in conceptual and mass balanced ecosystem models, were applied to outline a model management plan as well as site-specific management plans for the seamounts investigated. OASIS addressed five main objectives: Objective 1: To identify and describe the physical forcing mechanisms effecting seamount systems Objective 2: To assess the origin, quality and dynamics of particulate organic material within the water column and surface sediment at seamounts. Objective 3: To describe aspects of the biodiversity and the ecology of seamount biota, to assess their dynamics and the maintenance of their production. Objective 4: Modelling the trophic ecology of seamount ecosystems. Objective 5: Application of scientific knowledge to practical conservation.

Biomass of seston in the benthic layer of the Southwestern Indian Ocean

At stations to 1530 m depth in the Mozambique Channel and on the Saya-de-Malha and Walters banks seston biomass 2 m above the bottom was lower than at 30 m. Above the Walters shoal this difference was 13.2 mg/m**3 and was not equal to zero for P < 0.001. These results contradict previous ideas of biomass increase in benthic layers. The most likely cause of the observed impoverishment of plankton may be predominant consumption of living zooplankton component of seston by bottom and near-bottom predators. In the area of the Walters shoal this consumption is estimated as being about 300 mg/m**2 per day. Animals inhabiting this area live mainly on plankton brought in by horizontal advection, so that existence of faunal assemblages even on shallow-water submarine elevations is supported not mainly by local photosynthesis, but by primary production of surrounding waters.

Perlongher y ayahuasca : La antropología como una forma bastarda de realismo

Se propone una reflexión en torno a las diferencias que Perlongher percibe entre la producción de una escritura "en académico" (cuya obligación contractual sustentaba su "frugal manducar") y la expresión poética como forma del éxtasis (como una manera de dar forma a la fuerza de la deriva). Se tomarán como punto de partida los ensayos compilados en Prosa plebeya bajo el rubro "Antropología del éxtasis", escritos entre 1990 y 1991; asimismo, las entrevistas concedidas en la etapa final de su vida (1991-1992), reunidas en Papeles insumisos. Si en la "Introducción" de La prostitución masculina, Perlongher denominó a la antropología como una "ciencia de lo sutil" (contrapuesta a la rigidez técnica de la sociología, la estadística moral), en la última de sus entrevistas, la definió como "una forma bastarda de realismo", claramente relacionada con lo literario. La articulación entre antropología y literatura no es nueva, baste recordar las experiencias de Leiris, Carpentier, Arguedas y, más recientemente, los tanteos de la antropología poética chilena. Relaciono la singularidad perlongheriana a la constitución de territorios afectivos, cartografías de estados de ánimo, a través de una escritura barroca, barrial, barrosa, en la que los avatares de poeta y de profesor cohabitan el mismo escenario

Reflexiones sobre escepticismo y relativismo

Fil: Di Gregori, María Cristina. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.