Growth textures of thick sputtered films and multilayers assessed via synchrotron transmission Laue

The growth textures of thick sputtered Mo metallizations and Mo/W multilayers, were characterized via a synchrotron white‐beam (WB) x‐ray transmission Laue technique. Transmission x‐ray diffraction studies of Mo specimens up to 61 μm thick were performed with WB synchrotron radiation; while the practical thickness limit for similar observations using a conventional laboratory Cu K(α) x‐ray source is ten times smaller. This unique approach used polychromatic x rays to simultaneously produce diffraction from a wide spread of orientations of many crystallographic planes for all the grains within a relatively large specimen volume (≊60×106 μm3). These patterns were obtained for polycrystalline 31‐ and 61‐μm‐thick Mo/W multilayer specimens, and a 35‐μm‐thick‐monolithic Mo foil specimen. In all three cases the alignment of specimen grains was similar to what would be expected for single‐crystal transmission patterns, except that the recorded intensity distributed was less localized. The WB transmission images were indexed using a reciprocal space construction for the Laue case. In the multilayers, the grains were oriented out‐of‐plane such that 〈110〉 crystallographic planes were aligned in the direction of sputter growth, while in the monolithic Mo specimen 〈111〉 crystallographic planes were so aligned, i.e., perpendicular to the deposition substrate. A spread in orientation of ∼5° was measured in the multilayer specimens, while the monolithic Mo specimen showed a spread of ∼30° when compared to a perfect single‐crystal orientation. Preferred orientation was also observed within the plane of growth to varying degrees for all three samples. © 1995 American Institute of Physics.  Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71326/2/JAPIAU-78-6-3812-1.pd

Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.

Alterations of Ca2+ homeostasis have been implicated in a wide range of neurodegenerative diseases. Ca2+ efflux from the endoplasmic reticulum into the cytoplasm is controlled by binding of inositol 1,4,5-trisphosphate to its receptor. Activated inositol 1,4,5-trisphosphate receptors are then rapidly degraded by the endoplasmic reticulum-associated degradation pathway. Mutations in genes encoding the neuronal isoform of the inositol 1,4,5-trisphosphate receptor (ITPR1) and genes involved in inositol 1,4,5-trisphosphate receptor degradation (ERLIN1, ERLIN2) are known to cause hereditary spastic paraplegia (HSP) and cerebellar ataxia. We provide evidence that mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts, mutant SH-SY5Y cells and by gene knockdown in zebrafish. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias and cerebellar ataxias and thus prioritize this pathway for therapeutic interventions

Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness

Several hundred genetic muscle diseases have been described, all of which are rare. Their clinical and genetic heterogeneity means that a genetic diagnosis is challenging. We established an international consortium, MYO-SEQ, to aid the work-ups of muscle disease patients and to better understand disease etiology. Exome sequencing was applied to 1001 undiagnosed patients recruited from more than 40 neuromuscular disease referral centers; standardized phenotypic information was collected for each patient. Exomes were examined for variants in 429 genes associated with muscle conditions. We identified suspected pathogenic variants in 52% of patients across 87 genes. We detected 401 novel variants, 116 of which were recurrent. Variants in CAPN3, DYSF, ANO5, DMD, RYR1, TTN, COL6A2, and SGCA collectively accounted for over half of the solved cases; while variants in newer disease genes, such as BVES and POGLUT1, were also found. The remaining well-characterized unsolved patients (48%) need further investigation. Using our unique infrastructure, we developed a pathway to expedite muscle disease diagnoses. Our data suggest that exome sequencing should be used for pathogenic variant detection in patients with suspected genetic muscle diseases, focusing first on the most common disease genes described here, and subsequently in rarer and newly characterized disease genes

Neugeborenenscreening auf spinale Muskelatrophie

<jats:title>Zusammenfassung</jats:title><jats:p>Im Dezember 2020 hat der Gemeinsame Bundesausschuss beschlossen, dass das Screening auf spinale Muskelatrophie (SMA) in das allgemeine Neugeborenenscreening aufgenommen werden soll. Grundlage dieser Entscheidung war die Tatsache, dass inzwischen gezielte Behandlungsmöglichkeiten für die Patienten mit SMA zur Verfügung stehen und der Zeitpunkt, zu dem die Behandlung begonnen wird, entscheidend für den Erfolg der Therapie ist.</jats:p><jats:p>Das Neugeborenenscreening auf eine SMA basiert auf dem Nachweis einer homozygoten Deletion von Exon 7 im <jats:italic>SMN1</jats:italic>-Gen durch eine molekulargenetische Analyse aus der Trockenblutkarte. In allen Fällen muss eine Bestätigungsdiagnostik aus einer zweiten Blutprobe im Rahmen der Konfirmationsdiagnostik mit Bestimmung der <jats:italic>SMN2</jats:italic>-Kopien-Zahl durchgeführt werden. Die weitere Beratung und Therapie sollten in einer neuropädiatrischen Ambulanz mit Erfahrung in der Betreuung von Kindern mit SMA erfolgen.</jats:p&gt

Directing intracellular supramolecular assembly with N-heteroaromatic quaterthiophene analogues

Self-assembly of synthetic molecules in living cells can influence cell function, but is extremely challenging due to the complex environment of cells. Here the authors report the self-assembly of small organic molecules that locate, target and self-report their supramolecular behavior in living cells