Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum

Engineering design of vertical test stand cryostat

Under Indian Institutions and Fermilab collaboration, Raja Ramanna Centre for Advanced Technology and Fermi National Accelerator Laboratory are jointly developing 2K Vertical Test Stand (VTS) cryostats for testing SCRF cavities at 2K. The VTS cryostat has been designed for a large testing aperture of 86.36 cm for testing of 325 MHz Spoke resonators, 650 MHz and 1.3 GHz multi-cell SCRF cavities for Fermilab's Project-X. Units will be installed at Fermilab and RRCAT and used to test cavities for Project-X. A VTS cryostat comprises of liquid helium (LHe) vessel with internal magnetic shield, top insert plate equipped with cavity support stand and radiation shield, liquid nitrogen (LN{sub 2}) shield and vacuum vessel with external magnetic shield. The engineering design and analysis of VTS cryostat has been carried out using ASME B&PV Code and Finite Element Analysis. Design of internal and external magnetic shields was performed to limit the magnetic field inside LHe vessel at the cavity surface <1 {micro}T. Thermal analysis for LN{sub 2} shield has been performed to check the effectiveness of LN{sub 2} cooling and for compliance with ASME piping code allowable stresses

Engineering design and development of shielding door and safety shutter for transfer line-3 tunnel of Indus accelerator complex

794-797Indus accelerator complex houses two synchrotron radiation sources, Indus-1 and Indus-2. Electron beam from booster synchrotron is injected into Indus-2 through transfer line-3 (TL-3). In order to reduce the radiation coming from TL-3 through the door opening to Indus-1, to safe limit, a sliding shielding door has been developed. It is a close welded frame of mild steel with required thickness of shielding material in the form of interlocking lead bricks stacked inside. The door is suspended from an overhead I-beam attached to welded wall brackets, which are fixed to RCC wall using anchor fasteners. Pneumatic drive is used for moving the door. Radiation measurements carried out after the installation show substantial reduction in the radiation field at Indus-1 experimental hall. Another safety concern is the inadvertent transmission of electron beam from booster synchrotron to TL-3. For this purpose a safety shutter has been made. It comprises of a beam absorber made of high density alloy DENSIMET which can be moved in and out of electron beam path. Design, fabrication, installation and testing of sliding shielding door and the beam shutter have been described

Glu-108 in Saccharomyces cerevisiae Rad51 Is Critical for DNA Damage-Induced Nuclear Function

Rad51-mediated homologous recombination is the major mechanism for repairing DNA double-strand break (DSB) repair in cancer cells. Thus, regulating Rad51 activity could be an attractive target. The sequential assembly and disassembly of Rad51 to the broken DNA ends depend on reversible protein-protein interactions. Here, we discovered that a dynamic interaction with molecular chaperone Hsp90 is one such regulatory event that governs the recruitment of Rad51 onto the damaged DNA. We uncovered that Rad51 associates with Hsp90, and upon DNA damage, this complex dissociates to facilitate the loading of Rad51 onto broken DNA. In a mutant where such dissociation is incomplete, the occupancy of Rad51 at the broken DNA is partial, which results in inefficient DNA repair. Thus, it is reasonable to propose that any small molecule that may alter the dynamics of the Rad51-Hsp90 interaction is likely to impact DSB repair in cancer cells.</jats:p

Kontribusi Mazhab Teologis Mu'tazilah Dalam Perkembangan Sastra Arab Era Aabbasiyah Studi Analisis Kritis Historis: The Contribution of the Mu'tazilah Theological School to the Development of Arabic Literature During the Abbasid Era: A Critical Historical Analysis.

This research aims to reveal the contributions of the Mu'tazilah school of thought to the development of Arabic literature during the Abbasid dynasty. This study is important to ensure that today's generation of Muslims does not deny the achievements of Mu'tazilah writers of the Abbasid era due to theological differences. The main issue addressed in this research is the various forms of Mu'tazilah's contributions to the development of Arabic literature during the Abbasid dynasty. The reason for focusing on the Abbasid period is that during this time, the Mu'tazilah held a special place in the royal court, with Caliph al-Ma'mun even making Mu'tazilah the official ideology of the kingdom. This research is qualitative in nature, with data collected through library research. The theoretical framework employed is historical criticism theory, as the study's object involves historical facts of the Islamic golden age. The researcher concludes that the Mu'tazilah made significant contributions to the development of Arabic literature. These contributions are evident in the emergence of prominent literary figures and critics such as al-Jahiz, Abu Hayyan al-Tawhidi, and al-Qadi al-Jurjani. Moreover, they also contributed to the creation of new literary genres, including al-Munadharah, al-Jadal, al-Mawa'id, and al-Adab al-Dini. In light of these contributions, it is hoped that Muslim scholars in the field of Arabic language and literature will acknowledge these historical achievements. تهدف هذه الدراسة إلى الكشف عن إسهامات مذهب المعتزلة في تطور الأدب العربي خلال فترة الخلافة العباسية. تعتبر هذه الدراسة مهمة حتى لا تنكر الأجيال المسلمة اليوم الإنجازات التي حققها أدباء المعتزلة في العصر العباسي بسبب الاختلافات المذهبية اللاهوتية. تتمثل المشكلة الرئيسية في هذه الدراسة في أشكال إسهامات المعتزلة المختلفة في تطور الأدب العربي خلال فترة الخلافة العباسية. والسبب في التركيز على هذه الفترة هو أن المعتزلة كانوا يحظون بمكانة خاصة في البلاط الملكي خلال هذه الفترة، حيث جعل الخليفة المأمون مذهب المعتزلة أيديولوجية رسمية للمملكة. هذه الدراسة نوعية، وتم جمع البيانات من خلال البحث المكتبي. الإطار النظري المستخدم هو نظرية النقد التاريخي، لأن موضوع الدراسة يشمل الحقائق التاريخية للعصر الذهبي الإسلامي. وخلص الباحث إلى أن المعتزلة قدموا إسهامات كبيرة في تطور الأدب العربي. تتجلى هذه الإسهامات في ظهور شخصيات أدبية ونقاد بارزين مثل الجاحظ وأبو حيان التوحيدي والقاضي الجرجاني. علاوة على ذلك، أسهموا أيضًا في إنشاء أنواع أدبية جديدة، مثل: المناظرة، الجدل، المواعظ والأدب الديني. في ضوء هذه الإسهامات، يُأمل أن يعترف الباحثون المسلمون في مجال اللغة والأدب العربي بهذه الإنجازات التاريخية. Penelitian ini bertujuan untuk mengungkapkan kontribusi yang telah diberikan oleh mazhab teologis Islam mu’tazilah terhadap perkembangan sastra Arab pada masa dinasti Abbasiyah. Penelitian ini penting diungkapkan supaya generasi umat Islam hari ini tidak mengingkari dan terkesan menutup mata atas prestasi yang pernah diraih oleh para sastrawan Mu’tazilah era Abbasiyah, akibat dari perbedaan mazhab teologis. Permasalahan yang diajukan dalam penelitian ini adalah apa saja bentuk kontribusi mazhab teologi Mu’tazilah terhadap perkembangan sastra Arab masa dinasti Abbasiyah. Alasan penelitian ini dibatasi pada masa dinasti Abbasiyah karena pada masa itu kaum Mu’tazilah pernah mendapatkan tempat yang istimewa di istana, bahkan pada masa khalifah al-Ma’mun, Mu’tazilah menjadi ideologi resmi kerajaan. Adapun jenis penelitian ini adalah penelitian kualitatif. Sedangkan metode pengumpulan datanya dilakukan melalui penelitian perpustakaan. Teori yang digunakan adalah teori kritik sejarah karena objek kajiannya merupakan fakta-fakta historis masa lalu umat Islam di masa kejayaannya, Abbasiyah. Peneliti menemukan kesimpulan bahwa mazhab teologis Mu’tazilah pada masa dinasti Abbasiyah telah memberikan kontribusi yang nyata terhadap perkembangan sastra Arab. Kontribusi tersebut terlihat pada kemunculan tokoh-tokoh sastrawan dan kritikus sastra besar dan berpengaruh, di antaranya yang paling terkenal adalah al-Jahiz, Abu Hayyan al-Tauhidy dan al-Qadhi al-Jurjani. Selain itu, mereka juga turut menciptakan genre sastra baru, seperti: al-muna&gt;d}arah, al-jadal, al-mawa&gt;’id} dan al-adab al-di&gt;ni. Atas kontribusi ini, diharapkan para generasi umat Islam yang bergelut dalam bidang ilmu bahasa dan sastra Arab untuk bisa mengapresiasi atas prestasi para sastrawan Mu'tazilah tersebut dan tidak berupaya untuk menguburkannya hanya karena perbedaan mazhab teologis.   Kata Kunci: Sastrawan Mu’tazilah, Dinasti Abbasiyah, dan Analisis Kritis Histori

Isu Kebolehbacaan Teks Bahasa Arab Di Malaysia Keperluan Dan Pengukuran

Kebolehbacaan ialah tahap sesuatu bahan bacaan sama ada sukar atau senang yang boleh mempengaruhi kefahaman pembaca. Perbincangan kerta kerja ini memberikan penumpuan kepada dua isu utama yang berkait dengan kebolehbacaan, iaitu keperluan mengenal pasti tahap kebolehbacaan teks bahasa Arab yang digunakan sebagai bahan bacaan dalam kelas dan penggunaan instrumen untuk menentukan tahap kebolehbacaan tersebut. Sesuatu teks bacaan yang dipilih sebagai bahan pengajaran perlulah berada pada tahap yang sepadan dengan tahap kebolehan membaca pelajar. Hal ini merupakan satu keperluan kerana bahan bacaan yang sukar, jika diberikan kepada pelajar, akan merosakkan proses pembelajaran. Dalam konteks pengukuran tahap kebolehbacaan teks bahasa Arab pula, mutakhir ini beberapa formula kebolehbacaan bahasa Arab telah dicipta. Kewujudan formula-formula ini telah memberi nafas baru kepada kajian kebolehbacaan bahasa Arab kerana sebelum ini, penggunaan ujian kloz dan ujian kefahaman adalah antara alat ukur terbaik yang menjadi pilihan pengkaji

Glu-108 in Saccharomyces cerevisiae Rad51 Is Critical for DNA Damage-Induced Nuclear Function

Rad51-mediated homologous recombination is the major mechanism for repairing DNA double-strand break (DSB) repair in cancer cells. Thus, regulating Rad51 activity could be an attractive target. The sequential assembly and disassembly of Rad51 to the broken DNA ends depend on reversible protein-protein interactions. Here, we discovered that a dynamic interaction with molecular chaperone Hsp90 is one such regulatory event that governs the recruitment of Rad51 onto the damaged DNA. We uncovered that Rad51 associates with Hsp90, and upon DNA damage, this complex dissociates to facilitate the loading of Rad51 onto broken DNA. In a mutant where such dissociation is incomplete, the occupancy of Rad51 at the broken DNA is partial, which results in inefficient DNA repair. Thus, it is reasonable to propose that any small molecule that may alter the dynamics of the Rad51-Hsp90 interaction is likely to impact DSB repair in cancer cells.DNA damage-induced Rad51 focus formation is the hallmark of homologous recombination-mediated DNA repair. Earlier, we reported that Rad51 physically interacts with Hsp90, and under the condition of Hsp90 inhibition, it undergoes proteasomal degradation. Here, we show that the dynamic interaction between Rad51 and Hsp90 is crucial for the DNA damage-induced nuclear function of Rad51. Guided by a bioinformatics study, we generated a single mutant of Rad51, which resides at the N-terminal domain, outside the ATPase core domain. The mutant with an E to L change at residue 108 (Rad51E108L) was predicted to bind more strongly with Hsp90 than the wild-type (Rad51WT). A coimmunoprecipitation study demonstrated that there exists a distinct difference between the in vivo associations of Rad51WT-Hsp90 and of Rad51E108L-Hsp90. We found that upon DNA damage, the association between Rad51WT and Hsp90 was significantly reduced compared to that in the undamaged condition. However, the mutant Rad51E108L remained tightly associated with Hsp90 even after DNA damage. Consequently, the recruitment of Rad51E108L to the double-stranded broken ends was reduced significantly. The E108L-rad51 strain manifested severe sensitivity toward methyl methanesulfonate (MMS) and a complete loss of gene conversion efficiency, a phenotype similar to that of the Δrad51 strain. Previously, some of the N-terminal domain mutants of Rad51 were identified in a screen for a Rad51 interaction-deficient mutant; however, our study shows that Rad51E108L is not defective either in the self-interaction or its interaction with the members of the Rad52 epistatic group. Our study thus identifies a novel mutant of Rad51 which, owing to its greater association with Hsp90, exhibits a severe DNA repair defect