Students with dyslexia: research projects at Northumbria University

Northumbria University has about 700 registered disabled students, the majority of whom (around 58 per cent) are registered as having dyslexia and account for approximately two per cent of the total student population. Therefore dyslexic students represent the largest single group of disabled students and are those with whom most staff are likely to come into contact. The research authors were keen to ascertain whether there was a difference in academic performance between dyslexic and non-dyslexic students in respect of degree classification and assignment marks and to investigate whether dyslexic students generally felt supported in their academic studies. Research involved both qualitative and quantitative strands and the areas explored include pre expectations; general support throughout study; methods, flexibility and clarity of learning tasks, in particular assessment and levels of performance throughout and at the end of their study. This research is ongoing, however, findings have proved invaluable as a basis in the construction of good practice guidelines in dealing with the pedagogic needs of this diverse student grou

A Great Space Weather Event in February 1730

Aims. Historical records provide evidence of extreme magnetic storms with equatorward auroral extensions before the epoch of systematic magnetic observations. One significant magnetic storm occurred on February 15, 1730. We scale this magnetic storm with auroral extension and contextualise it based on contemporary solar activity. Methods. We examined historical records in East Asia and computed the magnetic latitude (MLAT) of observational sites to scale magnetic storms. We also compared them with auroral records in Southern Europe. We examined contemporary sunspot observations to reconstruct detailed solar activity between 1729 and 1731. Results. We show 29 auroral records in East Asian historical documents and 37 sunspot observations. Conclusions. These records show that the auroral displays were visible at least down to 25.8{\deg} MLAT throughout East Asia. In comparison with contemporary European records, we show that the boundary of the auroral display closest to the equator surpassed 45.1{\deg} MLAT and possibly came down to 31.5{\deg} MLAT in its maximum phase, with considerable brightness. Contemporary sunspot records show an active phase in the first half of 1730 during the declining phase of the solar cycle. This magnetic storm was at least as intense as the magnetic storm in 1989, but less intense than the Carrington event.Comment: 30 pages, 5 figures, and 2 tables, accepted for publication in Astronomy & Astrophysics on 25 April 2018. The figures and transcriptions/translations of historical documents are partially omitted in this manuscript due to the condition of reproduction. They are available in the publisher versio

Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes

<p>Abstract</p> <p>Background</p> <p>The genome of <it>Helicobacter pylori</it>, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian <it>H. pylori </it>genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains.</p> <p>Results</p> <p>A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including <it>oipA</it>, <it>hopMN</it>, <it>babABC</it>, <it>sabAB </it>and <it>vacA-2</it>) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (<it>tipα</it>), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (<it>miaA, tilS</it>), a DNA recombinase/exonuclease that recognizes genome identity (<it>addA</it>), and DNA/RNA hybrid nucleases (<it>rnhAB</it>). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of <it>cagA</it>, <it>vacA</it>, <it>homC </it>(outer membrane protein), <it>sotB </it>(sugar transport), and a translation fidelity factor (<it>miaA</it>). Large divergence was seen in genes related to antibiotics: <it>frxA </it>(metronidazole resistance), <it>def </it>(peptide deformylase, drug target), and <it>ftsA </it>(actin-like, drug target).</p> <p>Conclusions</p> <p>These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define <it>H. pylori </it>East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.</p

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

Efficacy of Mucosal Cutting Biopsy for the Histopathological Diagnosis of Gastric Submucosal Tumors

Background: Gastrointestinal stromal tumors occur frequently. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed commonly for diagnosis. However, the success rate of histological diagnosis is insufficient when the submucosal tumor (SMT) is small. Recently, another technique, mucosal cutting biopsy (MCB) has been reported. The aim of this study is to evaluate the efficacy and safety of MCB. Method: Between January 2012 and August 2018, MCB and EUS-FNA were performed 16 and 31 times for diagnosing gastric SMT. The diagnostic rate, the rate of successful immunohistochemistry, and the safety were reviewed. Difficult locations for EUS-FNA were also evaluated. Results: The mean SMT sizes measured on MCB and EUS-FNA were 21.2 and 36.2 mm. The diagnostic rates of MCB and EUS-FNA were almost the same (88 vs. 81%), but successful immunohistochemistry was significantly higher in the MCB group (93 vs. 59%, p = 0.03). In the subgroup of SMTs &#x3c; 20 mm, the successful histological diagnosis rate from EUS-FNA was relatively low. There were no complications. Failures of EUS-FNA were more frequent in the middle third of the stomach. Conclusions: MCB was an effective procedure for diagnosing gastric SMT, especially in the case of small SMTs located at the middle third of the stomach

Pregnancy and childbearing with nonclassic lipoid congenital adrenal hyperplasia without assisted reproductive technologies and sex hormone replacement : a case report

先天性副腎過形成症は、ステロイド合成酵素の欠損、コレステロールの輸送蛋白の異常により、副腎皮質過形成となる疾患で、うち、先天性リポイド副腎過形成（ lipoid congenital adrenal hyperplasia；LCAH）は、すべてのステロイド分泌不全が生じ、最も重症型である。コレステロールをミトコンドリア内に輸送する蛋白（Steroidogenic Acute Regulatory Protein；StAR）の異常により、生後早期から副腎不全症状を呈し、性ホルモン合成も障害される。一方、女性ホルモンの分泌にはStAR非依存性の回路も存在し、生殖補助医療下の妊娠出産例が報告されている。今回我々は、LCAH非古典型患者において、性ホルモンを補充せず妊娠出産に至った症例を経験した。【症例】27歳0回経妊0回経産。13歳時、遺伝子検査にてLCAH と診断。27歳時、自然妊娠。初期より女性ホルモン分泌不全はなく、妊娠37週5日、選択的帝王切開術にて健常児を得た。【考察】LCAH 非古典型患者において、性ホルモン補充を行わず、妊娠出産管理を行いうる可能性が示唆された。雑誌掲載論

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection