A misplaced lncRNA causes brachydactyly in humans

Translocations are chromosomal rearrangements that are frequently associated with a variety of disease states and developmental disorders. We identified 2 families with brachydactyly type E (BDE) resulting from different translocations affecting chromosome 12p. Both translocations caused downregulation of the parathyroid hormone-like hormone (PTHLH) gene by disrupting the cis-regulatory landscape. Using chromosome conformation capturing, we identified a regulator on chromosome 12q that interacts in cis with PTHLH over a 24.4-megabase distance and in trans with the sex-determining region Y-box 9 (SOX9) gene on chromosome 17q. The element also harbored a long noncoding RNA (lncRNA). Silencing of the lncRNA, PTHLH, or SOX9 revealed a feedback mechanism involving an expression-dependent network in humans. In the BDE patients, the human lncRNA was upregulated by the disrupted chromosomal association. Moreover, the lncRNA occupancy at the PTHLH locus was reduced. Our results document what we believe to be a novel in cis- and in trans-acting DNA and lncRNA regulatory feedback element that is reciprocally regulated by coding genes. Furthermore, our findings provide a systematic and combinatorial view of how enhancers encoding lncRNAs may affect gene expression in normal development

Neurolymphomatosis mimicking neurosarcoidosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Both neurosarcoidosis and central nervous system lymphoma can be very difficult to diagnose. We describe the case of a patient in whom neurosarcoidosis was strongly suspected, but who was eventually found to have lymphoma. We believe the case to be of interest and practical value to neurologists, oncologists and internists with an interest in inflammatory diseases.</p> <p>Case presentation</p> <p>A diagnosis of neurosarcoidosis was considered in a 49-year-old Caucasian man on the basis of the following symptoms and indications: a cough, bilateral hilar lymphadenopathy confirmed by thoracic computed tomography, the development of an S1 radiculopathy, cerebrospinal fluid abnormalities (raised protein level), bilateral lung hilar and lachrymal gland uptake on a gallium scan, and erythema nodosum confirmed with skin biopsy. These were followed by the development of multiple cranial neuropathies, including seventh nerve palsy. Exhaustive further investigations yielded no evidence for an alternative diagnosis. Treatments with steroids, cyclophosphamide, intravenous immunoglobulin and finally infliximab were of no benefit. He eventually developed cutaneous nodules, a biopsy of which revealed lymphoma that proved resistant to therapy.</p> <p>Conclusion</p> <p>Constant diagnostic vigilance is required in disorders such as neurosarcoidosis.</p

Knowledge translation on dementia: a cluster randomized trial to compare a blended learning approach with a "classical" advanced training in GP quality circles

<p>Abstract</p> <p>Background</p> <p>Thus far important findings regarding the dementia syndrome have been implemented into patients' medical care only inadequately. A professional training accounting for both, general practitioners' (GP) needs and learning preferences as well as care-relevant aspects could be a major step towards improving medical care. In the WIDA-study, entitled "Knowledge translation on dementia in general practice" two different training concepts are developed, implemented and evaluated. Both concepts are building on an evidence-based, GP-related dementia guideline and communicate the guideline's essential insights.</p> <p>Methods/Design</p> <p>Both development and implementation emphasize a procedure that is well-accepted in practice and, thus, can achieve a high degree of external validity. This is particularly guaranteed through the preparation of training material and the fact that general practitioners' quality circles (QC) are addressed. The evaluation of the two training concepts is carried out by comparing two groups of GPs to which several quality circles have been randomly assigned. The primary outcome is the GPs' knowledge gain. Secondary outcomes are designed to indicate the training's potential effects on the GPs' practical actions. In the first training concept (study arm A) GPs participate in a structured case discussion prepared for by internet-based learning material ("blended-learning" approach). The second training concept (study arm B) relies on frontal medical training in the form of a slide presentation and follow-up discussion ("classical" approach).</p> <p>Discussion</p> <p>This paper presents the outline of a cluster-randomized trial which has been peer reviewed and support by a national funding organization – Federal Ministry of Education and Research (BMBF) – and is approved by an ethics commission. The data collection has started in August 2006 and the results will be published independently of the study's outcome.</p> <p>Trial Registration</p> <p>Current Controlled Trials [ISRCTN36550981]</p

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

Validation of fluorescence-labeled artificial nonhuman sequences for single-strand conformation polymorphism mutation detection in familial hypercholesterolemia

We developed a two-in-one, polymerase chain reaction (PCR)-based method with a specific amplification step and a universal amplification step in one tube to screen for the presence of DNA variations. The method relies on fluorescence-labeled artificial nonhuman sequences for mutation detection. To document utility, we applied this method as a high-throughput capillary single-strand conformation polymorphism screening system to identify 30 mutations in the low-density lipoprotein receptor gene. The sensitivity of mutant allele detection compared to wild-type allele detection was 93%. We conclude that the “two-in-one PCR“ is sensitive, simple, and cost effective