The Receptor for Advanced Glycation End Products (RAGE) Affects T Cell Differentiation in OVA Induced Asthma

The receptor for glycation end products (RAGE) has been previously implicated in shaping the adaptive immune response. RAGE is expressed in T cells after activation and constitutively in T cells from patients with diabetes. The effects of RAGE on adaptive immune responses are not clear: Previous reports show that RAGE blockade affects Th1 responses. To clarify the role of RAGE in adaptive immune responses and the mechanisms of its effects, we examined whether RAGE plays a role in T cell activation in a Th2 response involving ovalbumin (OVA)-induced asthma in mice. WT and RAGE deficient wild-type and OT-II mice, expressing a T cell receptor specific for OVA, were immunized intranasally with OVA. Lung cellular infiltration and T cell responses were analyzed by immunostaining, FACS, and multiplex bead analyses for cytokines. RAGE deficient mice showed reduced cellular infiltration in the bronchial alveolar lavage fluid and impaired T cell activation in the mediastinal lymph nodes when compared with WT mice. In addition, RAGE deficiency resulted in reduced OT-II T cell infiltration of the lung and impaired IFNγ and IL-5 production when compared with WT mice and reduced infiltration when transferred into WT hosts. When cultured under conditions favoring the differentiation of T cells subsets, RAGE deficient T cells showed reduced production of IFNγ but increased production of IL-17. Our data show a stimulatory role for RAGE in T activation in OVA-induced asthma. This role is largely mediated by the effects of RAGE on T cell proliferation and differentiation. These findings suggest that RAGE may play a regulatory role in T cell responses following immune activation

Molecular cytogenetic analysis of patients with holoprosencephaly and structural rearrangements of 7q

The holoprosencephaly (HPE) sequence is a malformation complex with abnormal midline cleavage of the embryonic forebrain. HPE is genetically heterogeneous with at least 6 different chromosome regions containing genes involved in the expression of the phenotype. HPE3, recently identified as the human Sonic hedgehog gene, is localized to 7q36. We have used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) amplification in 5 cell lines from patients with HPE (3 cases), HPE and sacral agenesis (1 case), and microcephaly (1 case) to further define the structural rearrangements of the long arm of chromosome 7 in each case. All cell lines demonstrated loss of material in the critical region of HPE3 at band 7q36, which includes the Sonic hedgehog gene. We report here the analysis of these patient cell lines

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

RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses

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