PERANG SALIB III (Faktor Penyebab, Peran dan Perjuangan Shalahuddin Al Ayyubi)

M. Iqbal Hasby A. 1411315000. PERANG SALIB III (FAKTOR PENYEBAB, PERAN DAN PERJUANGAN SHALAHUDDIN AL AYYUBI). Skripsi. Jurusan Sejarah Kebudayaan Islam. Fakultas Adab Dakwah. IAIN Syekh Nurjati Cirebon. 2016. Perang Salib merupakan sebuah peristiwa peperangan yang terjadi dalam kurun waktu kurang lebih dua ratus tahun (1096-1292 M), yang mempertemukan Umat Islam dan Kristen Eropa demi mendapatkan kekuasaan atas wilayah Baitul Maqdis (Yerusalem). Dalam serangkaian Perang Salib ini telah memunculkan peran seorang tokoh yang cukup berjasa besar peranannya dalam mempertahankan Baitul Maqdis (Yerusalem), dia adalah seorang raja dan pahlawan umat Islam yaitu Shalahuddin Al Ayyubi. Sesuai dengan latar belakang yang telah di ungkapkan di atas, di sini penulis mencoba menguraikan rumusan masalah mengenai latar belakang perang salib dan sejauh mana peran dan perjuangan Shalahuddin Al Ayyubi dalam peristiwa Perang Salib, yang dirumuskan ke dalam pembahasan terkait latar belakang terjadinya perang salib serta peran dan perjuangan yang dimunculkan oleh Shalahuddin Al Ayyubi dalam peristiwa Perang Salib tersebut. Peristiwa ini memfokuskan pembahasannya pada peran penting seorang Shalahuddin dalam mempertahankan Baitul Maqdis (Yerusalem) saat Perang Salib III (1096 s/d 1198 M) sehingga tetap di dalam kekuasaan Umat Muslim. Untuk metode penelitian ini penulis menggunakan pendekatan Library Research dengan menggunakan metode heuristik, di mana setelah sumber-sumber informasi terkait diperoleh, berikutnya dilakukan kritik dan verivikasi kemudian dibuat alur yang logis dengan penafsiran-penafsiran agar apa yang penulis tulis memiliki alur cerita sejarah yang runtut dengan metode historiografi. Dari hasil penelitian tersebut dapat ditarik sebuah kesimpulan bahwa Perang Salib terjadi kurang lebih selama 200 tahun yang memperebutkan wilayah (Baitul Maqdis/Yerusalem) yang diangap suci oleh 3 agama besar (Yahudi, Kristen dan Islam) karena faktor Agama, faktor Politik (Kekuasaan), dan faktor Ekonomi. Shalahuddin Al Ayyubi menjadi tokoh yang paling dikenal dalam peristiwa Perang Salib ini, peran dan perjuangannya yang cukup berarti demi mempertahankan Baitul Maqdis (Yerusalem) dari serangan Pasukan Salib Eropa. Kata Kunci : Perang Salib, Shalahuddin Al Ayyubi, Peran dan perjuanga

Elevated transgelin reduces function of endothelial colony forming cells from gestational diabetic pregnancies

poster abstractFetal exposure to maternal diabetes predisposes children to future complications including hypertension and cardiovascular disease. A key mechanism by which these complications are thought to occur and persist is through the functional impairment of vascular progenitor cells, including endothelial colony forming cells (ECFCs). Previously, we showed that ECFCs exposed to gestational diabetes exhibit functional deficits, such as impaired vessel formation, but also differential gene expression compared to uncomplicated controls. One gene that was confirmed to be significantly upregulated in ECFCS from diabetic pregnancies was transgelin, an actin-binding smooth muscle protein. However, the functional consequences of increased transgelin in ECFCs are unknown. Therefore, to determine if transgelin is sufficient and required to induce dysfunction of ECFCs from diabetic pregnancies, transgelin protein levels were manipulated using genetic methods. Specifically, lentiviral overexpression and siRNA knockdown techniques were used in ECFCs from control and diabetic pregnancies respectively. Network formation assays and trans-well migration assays were performed to assess whether alteration of transgelin levels impact ECFC vasculogenesis and migration. Decreasing transgelin expression in diabetes-exposed ECFCs increased network formation (n=15, p<0.05) and cell migration (n=12, p<0.05). Conversely, overexpression of transgelin in ECFCs from uncomplicated pregnancies decreased network formation (n=12, p<0.05). Additional studies are underway to further elucidate intracellular signaling altered as a result of increased transgelin expression in diabetes-exposed ECFCs. Delineating the mechanisms underlying ECFC functional deficits will aid in the understanding of how and why chronic vascular complications persist in children born to mothers with diabetes

TgATAT-Mediated α-Tubulin Acetylation Is Required for Division of the Protozoan Parasite Toxoplasma gondii

Toxoplasma gondii is a widespread protozoan parasite that causes potentially life-threatening opportunistic disease. New inhibitors of parasite replication are urgently needed, as the current antifolate treatment is also toxic to patients. Microtubules are essential cytoskeletal components that have been selectively targeted in microbial pathogens; further study of tubulin in Toxoplasma may reveal novel therapeutic opportunities. It has been noted that α-tubulin acetylation at lysine 40 (K40) is enriched during daughter parasite formation, but the impact of this modification on Toxoplasma division and the enzyme mediating its delivery have not been identified. We performed mutational analyses to provide evidence that K40 acetylation stabilizes Toxoplasma microtubules and is required for parasite replication. We also show that an unusual Toxoplasma homologue of α-tubulin acetyltransferase (TgATAT) is expressed in a cell cycle-regulated manner and that its expression peaks during division. Disruption of TgATAT with CRISPR/Cas9 ablates K40 acetylation and induces replication defects; parasites appear to initiate mitosis yet exhibit incomplete or improper nuclear division. Together, these findings establish the importance of tubulin acetylation, exposing a new vulnerability in Toxoplasma that could be pharmacologically targeted. IMPORTANCE Toxoplasma gondii is an opportunistic parasite that infects at least one-third of the world population. New treatments for the disease (toxoplasmosis) are needed since current drugs are toxic to patients. Microtubules are essential cellular structures built from tubulin that show promise as antimicrobial drug targets. Microtubules can be regulated by chemical modification, such as acetylation on lysine 40 (K40). To determine the role of K40 acetylation in Toxoplasma and whether it is a liability to the parasite, we performed mutational analyses of the α-tubulin gene. Our results indicate that parasites cannot survive without K40 acetylation unless microtubules are stabilized with a secondary mutation. Additionally, we identified the parasite enzyme that acetylates α-tubulin (TgATAT). Genetic disruption of TgATAT caused severe defects in parasite replication, further highlighting the importance of α-tubulin K40 acetylation in Toxoplasma and its promise as a potential new drug target

Low Birth Weight and Risk of Progression to End Stage Renal Disease in IgA Nephropathy-A Retrospective Registry-Based Cohort Study.

Low Birth Weight (LBW) is a surrogate for fetal undernutrition and is associated with impaired nephron development in utero. In this study, we investigate whether having been born LBW and/or small for gestational age (SGA) predict progression to ESRD in IgA nephropathy (IgAN) patients. Retrospective registry-based cohort study. The Medical Birth Registry has recorded all births since 1967 and the Norwegian Renal Registry has recorded all patients with ESRD since 1980. Based on data from the Norwegian Kidney Biopsy Registry we included all patients diagnosed with IgAN in Norway from 1988-2013. These registries were linked and we analysed risk of progression to ESRD associated with LBW (defined as birth weight less than the 10th percentile) and/or SGA (defined as birth weight less than the 10th percentile for gestational week) by Cox regression statistics. We included 471 patients, of whom 74 developed ESRD. As compared to patients without LBW, patients with LBW had a hazard ratio (HR) of 2.0 (95% confidence interval 1.1-3.7) for the total cohort, 2.2 (1.1-4.4) for males and 1.3 (0.30-5.8) for females. Corresponding HRs for SGA were 2.2 (1.1-4.2), 2.7 (1.4-5.5) and 0.8 (0.10-5.9). Further analyses showed that as compared to patients with neither LBW nor SGA, patients with either SGA or LBW did not have significantly increased risks (HRs of 1.3-1.4) but patients who were both LBW and SGA had an increased risk (HR 3.2 (1.5-6.8). Mean duration of follow-up only 10 years and maximum age only 46 years. Among IgAN patients, LBW and/or SGA was associated with increased risk for progression to ESRD, the association was stronger in males

Kinetic Analysis of Vasculogenesis Quantifies Dynamics of Vasculogenesis and Angiogenesis In Vitro

Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis has become a central readout of endothelial progenitor cell functionality, and therefore, several attempts have been made to improve both in vitro and in vivo vasculogenesis models. However, standard methods are limited in scope, with static measurements failing to capture many aspects of this highly dynamic process. Therefore, the goal of developing this novel protocol was to assess the kinetics of in vitro vasculogenesis in order to quantitate rates of network formation and stabilization, as well as provide insight into potential mechanisms underlying vascular dysfunction. Application of this protocol is demonstrated using fetal endothelial colony forming cells (ECFCs) exposed to maternal diabetes mellitus. Fetal ECFCs were derived from umbilical cord blood following birth, cultured, and plated in slides containing basement membrane matrix, where they underwent vasculogenesis. Images of the entire slide wells were acquired using time-lapse phase contrast microscopy over 15 hours. Images were analyzed for derivation of quantitative data using an analysis software called Kinetic Analysis of Vasculogenesis (KAV). KAV uses image segmentation followed by skeletonization to analyze network components from stacks of multi-time point phase contrast images to derive ten parameters (9 measured, 1 calculated) of network structure including: closed networks, network areas, nodes, branches, total branch length, average branch length, triple-branched nodes, quad-branched nodes, network structures, and the branch to node ratio. Application of this protocol identified altered rates of vasculogenesis in ECFCs obtained from pregnancies complicated by diabetes mellitus. However, this technique has broad implications beyond the scope reported here. Implementation of this approach will enhance mechanistic assessment and improve functional readouts of vasculogenesis and other biologically important branching processes in numerous cell types or disease states

High-resolution absorption spectroscopy of the OH 2Pi 3/2 ground state line

The chemical composition of the interstellar medium is determined by gas phase chemistry, assisted by grain surface reactions, and by shock chemistry. The aim of this study is to measure the abundance of the hydroxyl radical (OH) in diffuse spiral arm clouds as a contribution to our understanding of the underlying network of chemical reactions. Owing to their high critical density, the ground states of light hydrides provide a tool to directly estimate column densities by means of absorption spectroscopy against bright background sources. We observed onboard the SOFIA observatory the 2Pi3/2, J = 5/2 3/2 2.5 THz line of ground-state OH in the diffuse clouds of the Carina-Sagittarius spiral arm. OH column densities in the spiral arm clouds along the sightlines to W49N, W51 and G34.26+0.15 were found to be of the order of 10^14 cm^-2, which corresponds to a fractional abundance of 10^-7 to 10^-8, which is comparable to that of H_2O. The absorption spectra of both species have similar velocity components, and the ratio of the derived H_2O to OH column densities ranges from 0.3 to 1.0. In W49N we also detected the corresponding line of ^18OH

The optical spectrum of a large isolated polycyclic aromatic hydrocarbon: hexa-peri-hexabenzocoronene, C42H18

The first optical spectrum of an isolated polycyclic aromatic hydrocarbon large enough to survive the photophysical conditions of the interstellar medium is reported. Vibronic bands of the first electronic transition of the all benzenoid polycyclic aromatic hydrocarbon hexa-peri-hexabenzocoronene were observed in the 4080-4530 Angstrom range by resonant 2-color 2-photon ionization spectroscopy. The strongest feature at 4264 Angstrom is estimated to have an oscillator strength of f=1.4x10^-3, placing an upper limit on the interstellar abundance of this polycyclic aromatic hydrocarbon at 4x10^12 cm^-2, accounting for a maximum of ~0.02% of interstellar carbon. This study opens up the possibility to rigorously test neutral polycyclic aromatic hydrocarbons as carriers of the diffuse interstellar bands in the near future.Comment: 9 pages, 1 figure. Fixed a typo on the frequency of the 'b' ban

Oxygen isotopic ratios in galactic clouds along the line of sight towards Sagittarius B2

As an independent check on previous measurements of the isotopic abundance of oxygen through the Galaxy, we present a detailed analysis of the ground state rotational lines of 16OH and 18OH in absorption towards the giant molecular cloud complex, Sagittarius B2. We have modelled the line shapes to separate the contribution of several galactic clouds along the line of sight and calculate 16OH/18OH ratios for each of these features. The best fitting values are in the range 320-540, consistent with the previous measurements in the Galactic Disk but slightly higher than the standard ratio in the Galactic Centre. They do not show clear evidence for a gradient in the isotopic ratio with galactocentric distance. The individual 16OH column densities relative to water give ratios of [H2O/OH]=0.6-1.2, similar in magnitude to galactic clouds in the sight lines towards W51 and W49. A comparison with CH indicates [OH/CH] ratios higher than has been previously observed in diffuse clouds. We estimate OH abundances of 10^-7 - 10^-6 in the line of sight features.Comment: 10 pages, 6 figures, accepted for publication in A&

TgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite Toxoplasma gondii

New drugs to control infection with the protozoan parasite Toxoplasma gondii are needed as current treatments exert toxic side effects on patients. Approaches to develop novel compounds for drug development include screening of compound libraries and targeted inhibition of essential cellular pathways. We identified two distinct compounds that display inhibitory activity against the parasite's replicative stage: F3215-0002, which we previously identified during a compound library screen, and I-BET151, an inhibitor of bromodomains, the "reader" module of acetylated lysines. In independent studies, we sought to determine the targets of these two compounds using forward genetics, generating resistant mutants and identifying the determinants of resistance with comparative genome sequencing. Despite the dissimilarity of the two compounds, we recovered resistant mutants with nonsynonymous mutations in the same domain of the same gene, TGGT1_254250, which we found encodes a protein that localizes to the parasite mitochondrion (designated TgPRELID after the name of said domain). We found that mutants selected with one compound were cross resistant to the other compound, suggesting a common mechanism of resistance. To further support our hypothesis that TgPRELID mutations facilitate resistance to both I-BET151 and F3215-0002, CRISPR (clustered regularly interspaced short palindromic repeat)/CAS9-mediated mutation of TgPRELID directly led to increased F3215-0002 resistance. Finally, all resistance mutations clustered in the same subdomain of TgPRELID. These findings suggest that TgPRELID may encode a multidrug resistance factor or that I-BET151 and F3215-0002 have the same target(s) despite their distinct chemical structures. IMPORTANCE We report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite Toxoplasma gondii. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the development of new therapies for toxoplasmosis and other related parasitic diseases