ISO_q(3) and ISO_q(2,1)

We prove the embedding of ISO_q(3) \hook ISU^{ex}_{\sqrt{q}}(2) and ISO_q(2,1) \hook ISL^{ex}_q(2,R) as $^*$-algebras and give a Hilbert space representation of $ISU^{ex}_{\sqrt{q}}(2)$Comment: 10 pages, 12 figures, Late

Protein and RNA ADP-ribosylation detection is influenced by sample preparation and reagents used

The modification of substrates with ADP-ribose (ADPr) is im-portant in, for example, antiviral immunity and cancer. Recently, several reagents were developed to detect ADP-ribosylation; however, it is unknown whether they recognise ADPr, specific amino acid-ADPr linkages, or ADPr with the surrounding protein backbone. We first optimised methods to prepare extracts con-taining ADPr-proteins and observe that depending on the amino acid modified, the modification is heatlabile. We tested the re-activity of available reagents with diverse ADP-ribosylated pro-tein and RNA substrates and observed that not all reagents are equally suited for all substrates. Next, we determined cross -reactivity with adenylylated RNA, AMPylated proteins, and me-tabolites, including NADH, which are detected by some reagents. Lastly, we analysed ADP-ribosylation using confocal microscopy, where depending on the fixation method, either mitochondrion, nucleus, or nucleolus is stained. This study allows future work dissecting the function of ADP-ribosylation in cells, both on protein and on RNA substrates, as we optimised sample prepa-ration methods and have defined the reagents suitable for specific methods and substrates.Bio-organic Synthesi

Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition

A hybrid approach reveals the allosteric regulation of GTP cyclohydrolase I

Guanosine triphosphate (GTP) cyclohydrolase I (GCH1) catalyzes the conversion of GTP to dihydroneopterin triphosphate (H2NTP), the initiating step in the biosynthesis of tetrahydrobiopterin (BH4). Besides other roles, BH4 functions as cofactor in neurotransmitter biosynthesis. The BH4 biosynthetic pathway and GCH1 have been identified as promising targets to treat pain disorders in patients. The function of mammalian GCH1s is regulated by a metabolic sensing mechanism involving a regulator protein, GCH1 feedback regulatory protein (GFRP). GFRP binds to GCH1 to form inhibited or activated complexes dependent on availability of cofactor ligands, BH4 and phenylalanine, respectively. We determined high-resolution structures of human GCH1-GFRP complexes by cryoelectron microscopy (cryo-EM). Cryo-EM revealed structural flexibility of specific and relevant surface lining loops, which previously was not detected by X-ray crystallography due to crystal packing effects. Further, we studied allosteric regulation of isolated GCH1 by X-ray crystallography. Using the combined structural information, we are able to obtain a comprehensive picture of the mechanism of allosteric regulation. Local rearrangements in the allosteric pocket upon BH4 binding result in drastic changes in the quaternary structure of the enzyme, leading to a more compact, tense form of the inhibited protein, and translocate to the active site, leading to an open, more flexible structure of its surroundings. Inhibition of the enzymatic activity is not a result of hindrance of substrate binding, but rather a consequence of accelerated substrate binding kinetics as shown by saturation transfer difference NMR (STD-NMR) and site-directed mutagenesis. We propose a dissociation rate controlled mechanism of allosteric, noncompetitive inhibition

Arab-West Report 2012, Weeks 01-31: Social and Political Issues in Post-Revolutionary Egypt

This dataset contains 73 Arab-West Report special reports that were published in 2012. These reports are mostly commentary on the political and social developments following the January 25th revolution in Egypt. The reports consist of editorials, analyses, media critiques and Interviews conducted by Arab-West Report with religious clerics and political figures. Thematically, the reports revolve around: • The post-revolutionary parliament which was predominantly controlled by Islamists. • The dissolution of the parliament by the Supreme Constitutional Court and its later reinstatement by the former President Mursī. • The reports also discuss the controversies surrounding the 2012 Presidential elections between Aḥmed Shafīq (A former Prime Minister in Mubarak`s last formed government) and Muhammad Mursī, a member of the Muslim Brotherhood group. • The concerns of Copts who feared the rising influence of Islamist political powers and the infamous Maspero incident. The reports also highlighted the death of the prominent Coptic Pope Shenouda and the subsequent election of the successive Coptic Pope. • The disputed statistics and claims about the alleged influx of Coptic Christian Immigration to the West in the post-revolutionary period, as a result of their concerns over the possibility of an Islamist rule. • The debates that followed the predominant monopoly of Islamists over the Constitutional Assembly that was in charge of drafting Egypt’s first constitution since 1971, which brought to the table the concerns of liberal, Azhar and Church leaders and possibly the Supreme Council of the Armed forces, all of whom saw a great need to be represented in the composition of an assembly. • Articles shedding light on the controversial Article 2 of the Egyptian constitution which states that Islamic the Principles of Islamic Shar’ia law is the principal source of legislation in the Egyptian Republic. • A few documents addressing the Coptic youth protests’ movements that followed a number of sectarian incidents. • Interviews conducted by AWR with Presidential hopefuls such as Dr. ʿAbd al-Munʿim Abū al-Futūḥ

Erratum: Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome (The American Journal of Human Genetics (2018) 103(3) (431–439), (S0002929718302374), (10.1016/j.ajhg.2018.07.010))

(The American Journal of Human Genetics 103, 431–439; September 6, 2018) Lisa Weixler has been added to the author list for her experimental and scientific contributions to the biophysical analysis of wild-type and mutant proteins. Her contributions were already mentioned in the acknowledgments. The authors apologize for initially only listing her in the acknowledgments and for the inconvenience. The author list has been corrected online and appears correctly here, and Lisa Weixler's affiliation is indicated as footnote 3: Center for Molecular Medicine Cologne, Cologne, Germany