Autosomal dominant transmission of complicated hereditary spastic paraplegia due to a dominant negative mutation of KIF1A, SPG30 gene.

KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance. © The Author(s) 20171

Acute Necrotizing Encephalopathy: Diffusion MR Imaging and Localized Proton MR Spectroscopic Findings in Two Infants

In this report, we describe the findings of diffusion MR imaging and proton MR spectroscopy in two infants with acute necrotizing encephalopathy in which there was characteristic symmetrical involvement of the thalami. Diffusion MR images of the lesions showed that the observed apparent diffusion coefficient (ADC) decrease was more prominent in the first patient, who had more severe brain damage and a poorer clinical outcome, than in the second. Proton MR spectroscopy detected an increase in the glutamate/glutamine complex and mobile lipids in the first case but only a small increase of lactate in the second. Diffusion MR imaging and proton MR spectroscopy may provide useful information not only for diagnosis but also for estimating the severity and clinical outcome of acute necrotizing encephalopathy

Mini-Open Anterior Lumbar Interbody Fusion Combined with Lateral Lumbar Interbody Fusion in Corrective Surgery for Adult Spinal Deformity

Study DesignProspective observational study.PurposeTo introduce the techniques and present the surgical outcomes of mini-open anterior lumbar interbody fusion (ALIF) at the most caudal segments of the spine combined with lateral lumbar interbody fusion (LLIF) for the correction of adult spinal deformityOverview of LiteratureAlthough LLIF is increasingly used to correct adult spinal deformity, the correction of sagittal plane deformity with LLIF alone is reportedly suboptimal.MethodsThirty-two consecutive patients with adult spinal deformity underwent LLIF combined with mini-open ALIF at the L5–S1 or L4–S1 levels followed by 2-stage posterior fixation. ALIF was performed for a mean 1.3 levels and LLIF for a mean 2.7 levels. Then, percutaneous fixation was performed in 11 patients (percutaneous group), open correction with facetectomy with or without laminectomy in 16 (open group), and additional pedicle subtraction osteotomy (PSO) in 5 (PSO group). Spinopelvic parameters were compared preoperatively and postoperatively. Hospitalization data and clinical outcomes were recorded.ResultsNo major medical complications developed, and clinical outcomes improved postoperatively in all groups. The mean postoperative segmental lordosis was greater after ALIF (17.5°±5.5°) than after LLIF (8.1°±5.3°, p <0.001). Four patients (12.5%) had lumbar lordosis with a pelvic incidence of ±9° preoperatively, whereas this outcome was achieved postoperatively in 30 patients (93.8%). The total increase in lumbar lordosis was 14.7° in the percutaneous group, 35.3° in the open group, and 57.0° in the PSO group. The ranges of potential lumbar lordosis increase were estimated as 4°–25°, 23°–42°, and 45°–65°, respectively.ConclusionsMini-open ALIF combined with LLIF followed by posterior fixation may be a feasible technique for achieving optimal sagittal balance and reducing the necessity of more extensive surgery

Prediction of species composition ratios in pooled specimens of the Anopheles Hyrcanus group using quantitative sequencing

Background Plasmodium vivax is transmitted by members of the Anopheles Hyrcanus Group that includes six species in the Republic of Korea: Anopheles sinensis sensu stricto (s.s.), Anopheles pullus, Anopheles kleini, Anopheles belenrae, Anopheles lesteri, and Anopheles sineroides. Individual Anopheles species within the Hyrcanus Group demonstrate differences in their geographical distributions, vector competence and insecticide resistance, making it crucial for accurate species identification. Conventional species identification conducted using individual genotyping (or barcoding) based on species-specific molecular markers requires extensive time commitment and financial resources. Results A population-based quantitative sequencing (QS) protocol developed in this study provided a rapid estimate of species composition ratios among pooled mosquitoes as a cost-effective alternative to individual genotyping. This can be accomplished by using species- or group-specific nucleotide sequences of the mitochondrial cytochrome C oxidase subunit I (COI) and the ribosomal RNA internal transcribed spacer 2 (ITS2) region as species identification alleles in a two-step prediction protocol. Standard genomic DNA fragments of COI and ITS2 genes were amplified from each Anopheles species using group-specific universal primer sets. Following sequencing of the COI or ITS2 amplicons generated from sets of standard DNA mixtures, equations were generated via linear regression to predict species-specific nucleotide sequence frequencies at different positions. Species composition ratios between An. sineroides, An. pullus and An. lesteri were estimated from QS of the COI amplicons based on the mC.260A, mC.122C and mC.525C alleles at the first step, followed by the prediction of species composition ratios between An. sinensis, An. kleini and An. belenrae based on QS of the ITS2 amplicons using the rI.370G and rI.389T alleles. The COI copy number was not significantly different between species, suggesting the reliability of COI-based prediction. In contrast, ITS2 showed a slightly but significantly higher copy number in An. belenrae, requiring an adjustment of its predicted composition ratio. A blind test proved that predicted species composition ratios either from pooled DNA specimens or pooled mosquito specimens were not statistically different from the actual values, demonstrating that the QS-based prediction is accurate and reliable. Conclusions This two-step prediction protocol will facilitate rapid estimation of the species composition ratios in field-collected Anopheles Hyrcanus Group populations and is particularly useful for studying the vector ecology of Anopheles population and epidemiology of malaria.This research was supported by the Government-wide R&D Fund project for infectious disease research (GFID), Republic of Korea (Grant Number: HG18C0046) and the Armed Forces Health Surveillance Branch, Global Emerg‑ing Infections Surveillance and Response System (AFHSB-GEIS), Silver Spring, MD (ProMIS ID #P0131-20-ME-03). DE Lee was supported in part by Brain Korea 21 Plus Program

Epitaxial Growth of a Single-Crystal Hybridized Boron Nitride and Graphene layer on a Wide-Band Gap Semiconductor

Vertical and lateral heterogeneous structures of two-dimensional (2D) materials have paved the way for pioneering studies on the physics and applications of 2D materials. A hybridized hexagonal boron nitride (h-BN) and graphene lateral structure, a heterogeneous 2D structure, has been fabricated on single-crystal metals or metal foils by chemical vapor deposition (CVD). However, once fabricated on metals, the h-BN/graphene lateral structures require an additional transfer process for device applications, as reported for CVD graphene grown on metal foils. Here, we demonstrate that a single-crystal h-BN/graphene lateral structure can be epitaxially grown on a wide-gap semiconductor, SiC(0001). First, a single-crystal h-BN layer with the same orientation as bulk SiC was grown on a Si-terminated SiC substrate at 850 oC using borazine molecules. Second, when heated above 1150 oC in vacuum, the h-BN layer was partially removed and, subsequently, replaced with graphene domains. Interestingly, these graphene domains possess the same orientation as the h-BN layer, resulting in a single-crystal h-BN/graphene lateral structure on a whole sample area. For temperatures above 1600 oC, the single-crystal h-BN layer was completely replaced by the single-crystal graphene layer. The crystalline structure, electronic band structure, and atomic structure of the h-BN/graphene lateral structure were studied by using low energy electron diffraction, angle-resolved photoemission spectroscopy, and scanning tunneling microscopy, respectively. The h-BN/graphene lateral structure fabricated on a wide-gap semiconductor substrate can be directly applied to devices without a further transfer process, as reported for epitaxial graphene on a SiC substrate.Comment: 23 pages, 7 figure