ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment

Acyl CoA Oxidase 2 (ACOX2) encodes branched-chain acyl-CoA oxidase, a peroxisomal enzyme believed to be involved in the metabolism of branched-chain fatty acids and bile acid intermediates. Deficiency of this enzyme has not been described previously. We report an 8-y-old male with intermittently elevated transaminase levels, liver fibrosis, mild ataxia, and cognitive impairment. Exome sequencing revealed a previously unidentified homozygous premature termination mutation (p.Y69*) in ACOX2 Immunohistochemistry confirmed the absence of ACOX2 expression in the patient's liver, and biochemical analysis showed marked elevation of intermediate bile acids upstream of ACOX2. These findings define a potentially treatable inborn error of bile acid biosynthesis caused by ACOX2 deficiency

Etnografia de Retalhos: Diálogos, dilemas e perspectivas metodológicas feministas para a antropologia

Neste material estão compiladas a tradução para o português do Manifesto por uma Etnografia de Retalhos e uma entrevista inédita realizada com duas de suas autoras, Chika Watanabe e Gökçe Günel. A entrevista aconteceu em julho de 2022, através da plataforma Zoom, e serviu para conhecer os dilemas e as perspectivas da proposta de etnografia defendida pelas pesquisadoras. O encontro também serviu para amparar e refinar o exercício de tradução que estava em andamento, permitindo o diálogo direto a respeito da abordagem de retalhos e a identificação das formas com que a proposta pode ecoar na academia brasileira.In this material are compiled the Manifesto for Patchwork Ethnography Portuguese translation and an unpublished interview with two of its authors, Chika Watanabe and Gökçe Günel. The interview took place in July 2022 through the Zoom platform and helped us to learn more about the dilemmas and perspectives of the ethnography proposal defended by the researchers. The meeting also served to support and improve the translation that was in progress, allowing direct dialogue about the patchwork approach and the identification of the ways in which the proposal could resonate in Brazilian academia

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated de novo mutation (p.Cys188Trp) in the GABAA receptor Cl− channel γ-1 subunit (GABRG1) exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na+ and Ca+ channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca2+ channel Cav3.2 (CACNA1H). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1

تطوير المواد الدراسية في تعليم مهارة الكتاب في برنامج الخاض لتعليم اللغة العربية في جامعة مولانا مالك ابراهم الإسلامية الحكومية مالانج

ABSTRAK Perkembangan Universitas Islam Negeri Maulana Malik Ibrahim Malang sebagai salah satu Perguruan Tinggi Islam yang berkembang pesat membutuhkan terobosan- terobosan yang handal. Salah satu hal penting yang tidak bisa dipisahkan adalah peranan penting dari PKPBA (Program Khusus Pengembangan Bahasa Arab). PKPBA sebagai sebuah unit pengembangan bahasa, telah berperan penting dalam membantu meningkatkan kemampuan berbahasa mahasiswa khususnya bahasa arab. Banyak dari mahasiswa yang pertama kali masuk PKPBA belum mengetahui bahasa Arab. Namun setelah belajar di PKPBA mereka mampu mengenal ilmu bahasa arab. Namun, tidak hanya berhenti pada mengetahui bahasa arab saja, program ini juga berupaya agar semua mahasiswa mampu untuk menguasai salah satu dari 4 ketrampilan bahasa yakni ketrampilan menulis. Tujuan dari peneliyian ini adalah untuk melengkapi proses pengembangan penyusunan materi ajar menulis dan mengetahui ke-efektifan materi yang dikembangkan. Penelitian ini menggunakan prosedur eksperimen dimana peneliti mendisain Pre-test dan Postest terhadap dua kelompok yakni kelompok eksperimen dan kelompok kontrol. Hasil penelitian ini adalah bahwa pembelajaran ketrampilan menulis dengan menggunakan buku ajar lebih efektif dari pada tanpa menggunakan buku ajar. Dengan indikasi bahwa t-test kelas eksperimen (J3) lebih efektif dengan indikasi bahwa t-test kelas kontrol adalah 3,4. dimana hasil ini lebih besar dari pada tingkat t-table 5% 2,059 dan tingkat 1% 2,787. Dari hasil ini menunjukan bahwa pengajaran menulis bahasa Arab efektif dengan menggunakan materi ajar yang telah disusun oleh peneliti. Hasil penelitian ini adalah: (1) Penyusunan materi ajar untuk PKPBA dimulai dengan membatasi tujuan pengajaran, kemudian menentukan pembagian materi sesuai dengan jumlah hari yang digunakan untuk pembelajaran dalam satu minggu. (2) Pembelajaran menulis bahasa Arab dengan menggunakan Materi ajar ini dinyatakan efektif. Dari hasil yang disebutkan diatas, sudah semestinya materi pengajaran menulis bahasa Arab dapat dimanfaatkan dengan benar dalam proses pengajaran, selain itu penulis berharap agar penelitian ini menjadi referensi untuk penelitian lanjutan yang berhubungan dengan penelitian ini sehingga dapat dikembangkan ke dalam desain materi ajar menulis untuk tingkat selanjutnya. ABSTRACT The expansion of State Islamic University Maulana Malik Ibrahim need some powerful breakthrough. One of the important things is the role of Intensive Arabic Program as unit for improving Arabic, have played an important for helping Arabic language improvement. Most of the students when the first time they enter to this Program, they haven’t yet Arabic knowledge. But after studying in this program for several months they could understand about Arabic. But is not enough in knowing the Arabic only, but this program also try to make all students are mastering one of these four skills, that is writing skill. This research aims at designing process of writing teaching material and finding out the effectiveness of writing teaching material using in Intensive Arabic Program of State Islamic University of Maulana Malik Ibrahim Malang. This research uses the experimental method that the researcher design pre-test and post-test for both groups (Experiment and Control group). This research reach the degree of t-test 3,4 this biggest than t-table at the level of 5% (2,059) and at the level 1% (2,787). This indicates that the use of writing Teaching Material in Arabic for improving writing skill is effective. And the result of this research are obtained bellow: (1) Preparing this teaching material process started by determining the goals, finding out the learning material based on the days in a week which used for teaching (2) The use of writing Teaching Material in Arabic for improving writing skill is effective. Based on these results, teaching material must be used as good as possible in teaching process. Besides, the researcher hopes that the research becomes the reference for further researchers which have a relation with this chapter and could be developed to other teaching material for advance grade

Combining transbronchial aspiration with endobronchial and transbronchial biopsy in sarcoidosis

PubMed ID: 10441973This study was carried out to evaluate the diagnostic yield and safety of flexible transbronchial needle aspiration (TBNA), endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) combinations in stages I-III sarcoidosis (SA). Between 1989 and 1997, 74 patients suspected of having SA underwent fibreoptic bronchoscopay along with TBNA + EBB + TBLB or EBB + TBLB. During the same fibreoptic bronchoscopy, TBNA (using a 19-gauge histological needle and contrast-enhanced computed tomography (CT) guidance), EBB (from abnormal or normal bronchial mucosa) and TBLB were performed in stages I (n = 33) and II (n = 25), and EBB and TBLB in stage III (n = 16). The diagnosis of SA required the presence of noncaseating granulomas and the absence of 'allergic granulomatosis and angiitis with eosinophilic infiltration' or foreign body reaction, with negative Ziehl-Neelson and methenamine silver stains, as well as negative cultures for acid-fast bacilli, fungi and other organisms. TBNA was diagnostic in 20 (61%) and 10 (42%) cases of stages I and II, whereas EBB was diagnostic in 15 (45%), 12 (50%) and seven (58%) cases, of stages I, II and III, respectively, and TBLB in 17 (52%), 15 (63%) and 10 (83%). By means of TBNA, EBB and TBLB alone, the diagnostic yields were nine (27%), four (12%) and six (18%) cases in stage I, two (8%), four (17%) and seven (29%) in stage II, and two (17%) and five (42%) by EBB and TBLB in stage III, respectively. The diagnostic yield of TBNA + EBB + TBLB was 30 (91%) in stage I and 21 (88%) in stage II, and that of EBB + TBLB was 12 (100%) in stage III. Overall, 63 (91%) cases of SA were diagnosed by TBNA + EBB + TBLB and EBB + TBLB. In six of the eleven bronchoscopically-negative cases, mediastinoscopy (four) or thoracotomy (two) established the diagnosis of SA, whereas the remaining five were diagnosed along with non-sarcoidosis diseases (one case in stage II and four in stage III) by various tissue biopsies in the follow-up. The combination of TBNA + EBB + TBLB and EBB + TBLB provided an overall sensitivity and accuracy of 90% and a specificity of 100%. All six (9%) significant complications - pneumothorax (four) and 40-100 mL haemorrhage (two) - were attributable to TBLB. It is, therefore, inferred that the combination of transbronchial needle aspiration, endobronchial biopsy and transbronchial lung biopsy in stages I and II, and that of endobronchial biopsy and transbronchial lung biopsy in stage III, is safe and cost-effective as well as increasing the diagnostic yield, and should therefore be performed routinely in the diagnosis of sarcoidosis