ALBERT

Description: Thiopeptides are a subclass of ribosomally synthesized and posttranslationally modified peptides (RiPPs) with complex molecular architectures and an array of biological activities, including potent antimicrobial activity. Here we report the generation of thiopeptides containing noncanonical amino acids (ncAAs) by introducing orthogonal amber suppressor aminoacyl-tRNA synthetase/tRNA pairs into a thiocillin producer...

Description: Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld–Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1−/−) or neural crest (NC)-specific (NC-Foxc1−/−) null mutation display excessive growth of corneal blood and lymphatic vessels. This is associated with disorganization of the extracellular matrix and increased expression of multiple matrix metalloproteinases. Heterozygous mutants (Foxc1+/− and NC-Foxc1+/−) exhibit milder phenotypes, such as disrupted limbal vasculature. Moreover, environmental exposure to corneal injury significantly increases growth of both blood and lymphatic vessels in both Foxc1+/− and NC-Foxc1+/− mice compared with controls. Notably, this amplification of the angiogenic response is abolished by inhibition of VEGF receptor 2. Collectively, these findings identify a role for FoxC1 in inhibiting corneal angiogenesis, thereby maintaining corneal transparency by regulating VEGF signaling.

Description: In the 15 years since transcription factor mutation, and subsequently dosage alterations, were shown to account for a proportion of Axenfeld–Rieger syndrome cases, novel phenotypes continue to be defined. As illustrated by the spectrum of FOXC1-attributable CNS anomalies (1, 2), these are frequently present in a subset of cases and only identified by meticulous phenotyping. Our original article in PNAS (3) demonstrated that a proportion of patients with a mutation or altered FOXC1 gene dosage exhibited corneal angiogenesis, confirming our extensive data from multiple murine mutants regarding Foxc1’s role in maintaining corneal avascularity. In keeping with the heterogeneity of transcription...

Description: A homolog of the bacterial cell division gene ftsZ was isolated from the alga Mallomonas splendens. The nuclear-encoded protein (MsFtsZ-mt) was closely related to FtsZs of the alpha-proteobacteria, possessed a mitochondrial targeting signal, and localized in a pattern consistent with a role in mitochondrial division. Although FtsZs are known to act in the division of chloroplasts, MsFtsZ-mt appears to be a mitochondrial FtsZ and may represent a mitochondrial division protein.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beech, P L -- Nheu, T -- Schultz, T -- Herbert, S -- Lithgow, T -- Gilson, P R -- McFadden, G I -- New York, N.Y. -- Science. 2000 Feb 18;287(5456):1276-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, 221 Burwood Highway, Melbourne, 3125, Australia. plbeech@deakin.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10678836" target="_blank"〉PubMed〈/a〉

Description: Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943511/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943511/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Kai -- Zhang, Haitao -- Ma, Deqiong -- Bucan, Maja -- Glessner, Joseph T -- Abrahams, Brett S -- Salyakina, Daria -- Imielinski, Marcin -- Bradfield, Jonathan P -- Sleiman, Patrick M A -- Kim, Cecilia E -- Hou, Cuiping -- Frackelton, Edward -- Chiavacci, Rosetta -- Takahashi, Nagahide -- Sakurai, Takeshi -- Rappaport, Eric -- Lajonchere, Clara M -- Munson, Jeffrey -- Estes, Annette -- Korvatska, Olena -- Piven, Joseph -- Sonnenblick, Lisa I -- Alvarez Retuerto, Ana I -- Herman, Edward I -- Dong, Hongmei -- Hutman, Ted -- Sigman, Marian -- Ozonoff, Sally -- Klin, Ami -- Owley, Thomas -- Sweeney, John A -- Brune, Camille W -- Cantor, Rita M -- Bernier, Raphael -- Gilbert, John R -- Cuccaro, Michael L -- McMahon, William M -- Miller, Judith -- State, Matthew W -- Wassink, Thomas H -- Coon, Hilary -- Levy, Susan E -- Schultz, Robert T -- Nurnberger, John I -- Haines, Jonathan L -- Sutcliffe, James S -- Cook, Edwin H -- Minshew, Nancy J -- Buxbaum, Joseph D -- Dawson, Geraldine -- Grant, Struan F A -- Geschwind, Daniel H -- Pericak-Vance, Margaret A -- Schellenberg, Gerard D -- Hakonarson, Hakon -- 1U24MH081810/MH/NIMH NIH HHS/ -- HD055751/HD/NICHD NIH HHS/ -- HD055782-01/HD/NICHD NIH HHS/ -- HD055784/HD/NICHD NIH HHS/ -- M01-RR00064/RR/NCRR NIH HHS/ -- MH061009/MH/NIMH NIH HHS/ -- MH0666730/MH/NIMH NIH HHS/ -- MH080647/MH/NIMH NIH HHS/ -- MH081754/MH/NIMH NIH HHS/ -- MH64547/MH/NIMH NIH HHS/ -- MH69359/MH/NIMH NIH HHS/ -- N01-HD-4-3368/HD/NICHD NIH HHS/ -- N01-HD-4-3383/HD/NICHD NIH HHS/ -- NS049261/NS/NINDS NIH HHS/ -- NS26630/NS/NINDS NIH HHS/ -- NS36768/NS/NINDS NIH HHS/ -- P01 NS026630/NS/NINDS NIH HHS/ -- P01 NS026630-109001/NS/NINDS NIH HHS/ -- P50 HD055748/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- P50 HD055751-01/HD/NICHD NIH HHS/ -- P50 HD055782-01/HD/NICHD NIH HHS/ -- P50 HD055784/HD/NICHD NIH HHS/ -- P50 HD055784-01/HD/NICHD NIH HHS/ -- P50 HD055784-010002/HD/NICHD NIH HHS/ -- P50 HD055784-020002/HD/NICHD NIH HHS/ -- P50 HD055784-030002/HD/NICHD NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH061009-01A1/MH/NIMH NIH HHS/ -- R01 MH064547/MH/NIMH NIH HHS/ -- R01 MH064547-01/MH/NIMH NIH HHS/ -- R01 MH064547-01S1/MH/NIMH NIH HHS/ -- R01 MH064547-02/MH/NIMH NIH HHS/ -- R01 MH064547-02S1/MH/NIMH NIH HHS/ -- R01 MH064547-03/MH/NIMH NIH HHS/ -- R01 MH064547-04/MH/NIMH NIH HHS/ -- R01 MH064547-05/MH/NIMH NIH HHS/ -- R01 MH069359/MH/NIMH NIH HHS/ -- R01 MH069359-01A2/MH/NIMH NIH HHS/ -- R01 MH080647/MH/NIMH NIH HHS/ -- R01 MH080647-11/MH/NIMH NIH HHS/ -- R01 MH081754/MH/NIMH NIH HHS/ -- R01 MH081754-01/MH/NIMH NIH HHS/ -- R01 MH081754-02/MH/NIMH NIH HHS/ -- R01 NS036768/NS/NINDS NIH HHS/ -- R01 NS036768-06/NS/NINDS NIH HHS/ -- R01 NS049261/NS/NINDS NIH HHS/ -- R01 NS049261-01A2/NS/NINDS NIH HHS/ -- U54 MH066673/MH/NIMH NIH HHS/ -- U54 MH066673-01A10001/MH/NIMH NIH HHS/ -- UL1 RR024134/RR/NCRR NIH HHS/ -- UL1 RR024134-01/RR/NCRR NIH HHS/ -- UL1-RR024134-03/RR/NCRR NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2009 May 28;459(7246):528-33. doi: 10.1038/nature07999. Epub 2009 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Genomics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19404256" target="_blank"〉PubMed〈/a〉

Description: Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925224/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925224/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glessner, Joseph T -- Wang, Kai -- Cai, Guiqing -- Korvatska, Olena -- Kim, Cecilia E -- Wood, Shawn -- Zhang, Haitao -- Estes, Annette -- Brune, Camille W -- Bradfield, Jonathan P -- Imielinski, Marcin -- Frackelton, Edward C -- Reichert, Jennifer -- Crawford, Emily L -- Munson, Jeffrey -- Sleiman, Patrick M A -- Chiavacci, Rosetta -- Annaiah, Kiran -- Thomas, Kelly -- Hou, Cuiping -- Glaberson, Wendy -- Flory, James -- Otieno, Frederick -- Garris, Maria -- Soorya, Latha -- Klei, Lambertus -- Piven, Joseph -- Meyer, Kacie J -- Anagnostou, Evdokia -- Sakurai, Takeshi -- Game, Rachel M -- Rudd, Danielle S -- Zurawiecki, Danielle -- McDougle, Christopher J -- Davis, Lea K -- Miller, Judith -- Posey, David J -- Michaels, Shana -- Kolevzon, Alexander -- Silverman, Jeremy M -- Bernier, Raphael -- Levy, Susan E -- Schultz, Robert T -- Dawson, Geraldine -- Owley, Thomas -- McMahon, William M -- Wassink, Thomas H -- Sweeney, John A -- Nurnberger, John I -- Coon, Hilary -- Sutcliffe, James S -- Minshew, Nancy J -- Grant, Struan F A -- Bucan, Maja -- Cook, Edwin H -- Buxbaum, Joseph D -- Devlin, Bernie -- Schellenberg, Gerard D -- Hakonarson, Hakon -- 1U24MH081810/MH/NIMH NIH HHS/ -- HD055751/HD/NICHD NIH HHS/ -- HD055782-01/HD/NICHD NIH HHS/ -- HD35476/HD/NICHD NIH HHS/ -- M01 RR000064-340579/RR/NCRR NIH HHS/ -- M01 RR000064-350579/RR/NCRR NIH HHS/ -- M01 RR000064-35S10579/RR/NCRR NIH HHS/ -- M01 RR000064-35S10591/RR/NCRR NIH HHS/ -- M01 RR000064-35S10602/RR/NCRR NIH HHS/ -- M01 RR000064-35S20579/RR/NCRR NIH HHS/ -- M01 RR000064-35S20591/RR/NCRR NIH HHS/ -- M01 RR000064-35S20602/RR/NCRR NIH HHS/ -- M01 RR000064-360579/RR/NCRR NIH HHS/ -- M01 RR000064-360582/RR/NCRR NIH HHS/ -- M01 RR000064-360591/RR/NCRR NIH HHS/ -- M01 RR000064-36S10579/RR/NCRR NIH HHS/ -- M01 RR000064-36S10582/RR/NCRR NIH HHS/ -- M01 RR000064-36S10591/RR/NCRR NIH HHS/ -- M01 RR000064-370579/RR/NCRR NIH HHS/ -- M01 RR000064-370582/RR/NCRR NIH HHS/ -- M01 RR000064-370591/RR/NCRR NIH HHS/ -- M01 RR000064-37S10579/RR/NCRR NIH HHS/ -- M01 RR000064-37S10582/RR/NCRR NIH HHS/ -- M01 RR000064-37S10591/RR/NCRR NIH HHS/ -- M01 RR000064-380579/RR/NCRR NIH HHS/ -- M01 RR000064-380582/RR/NCRR NIH HHS/ -- M01 RR000064-380591/RR/NCRR NIH HHS/ -- M01 RR000064-390579/RR/NCRR NIH HHS/ -- M01 RR000064-390582/RR/NCRR NIH HHS/ -- M01 RR000064-390591/RR/NCRR NIH HHS/ -- M01-RR00064/RR/NCRR NIH HHS/ -- MH061009/MH/NIMH NIH HHS/ -- MH0666730/MH/NIMH NIH HHS/ -- MH64547/MH/NIMH NIH HHS/ -- MH69359/MH/NIMH NIH HHS/ -- NS049261/NS/NINDS NIH HHS/ -- P01 HD035476-03/HD/NICHD NIH HHS/ -- P01 HD035476-04/HD/NICHD NIH HHS/ -- P01 HD035476-04S1/HD/NICHD NIH HHS/ -- P01 HD035476-04S2/HD/NICHD NIH HHS/ -- P01 HD035476-05/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- P50 HD055751-01/HD/NICHD NIH HHS/ -- P50 HD055751-010002/HD/NICHD NIH HHS/ -- P50 HD055751-019003/HD/NICHD NIH HHS/ -- P50 HD055751-02/HD/NICHD NIH HHS/ -- P50 HD055751-020002/HD/NICHD NIH HHS/ -- P50 HD055751-03/HD/NICHD NIH HHS/ -- P50 HD055751-030002/HD/NICHD NIH HHS/ -- P50 HD055751-04/HD/NICHD NIH HHS/ -- P50 HD055782-01/HD/NICHD NIH HHS/ -- R01 MH057881/MH/NIMH NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH061009-01A1/MH/NIMH NIH HHS/ -- R01 MH061009-01A1S1/MH/NIMH NIH HHS/ -- R01 MH061009-02/MH/NIMH NIH HHS/ -- R01 MH061009-03/MH/NIMH NIH HHS/ -- R01 MH061009-04A1/MH/NIMH NIH HHS/ -- R01 MH061009-05/MH/NIMH NIH HHS/ -- R01 MH061009-06/MH/NIMH NIH HHS/ -- R01 MH061009-07/MH/NIMH NIH HHS/ -- R01 MH061009-08/MH/NIMH NIH HHS/ -- R01 MH064547/MH/NIMH NIH HHS/ -- R01 MH064547-01/MH/NIMH NIH HHS/ -- R01 MH064547-01S1/MH/NIMH NIH HHS/ -- R01 MH064547-02/MH/NIMH NIH HHS/ -- R01 MH064547-02S1/MH/NIMH NIH HHS/ -- R01 MH064547-03/MH/NIMH NIH HHS/ -- R01 MH064547-04/MH/NIMH NIH HHS/ -- R01 MH064547-05/MH/NIMH NIH HHS/ -- R01 MH069359/MH/NIMH NIH HHS/ -- R01 MH069359-01A2/MH/NIMH NIH HHS/ -- R01 MH069359-02/MH/NIMH NIH HHS/ -- R01 MH069359-03/MH/NIMH NIH HHS/ -- R01 MH069359-04/MH/NIMH NIH HHS/ -- R01 MH069359-05/MH/NIMH NIH HHS/ -- R01 NS049261/NS/NINDS NIH HHS/ -- R01 NS049261-01A2/NS/NINDS NIH HHS/ -- R01 NS049261-02/NS/NINDS NIH HHS/ -- R01 NS049261-03/NS/NINDS NIH HHS/ -- R01 NS049261-04/NS/NINDS NIH HHS/ -- R01 NS049261-05/NS/NINDS NIH HHS/ -- U10 MH066766-02S1/MH/NIMH NIH HHS/ -- U10MH66766-02S1/MH/NIMH NIH HHS/ -- U19 HD035476-06/HD/NICHD NIH HHS/ -- U19 HD035476-07/HD/NICHD NIH HHS/ -- U19 HD035476-08/HD/NICHD NIH HHS/ -- U19 HD035476-09/HD/NICHD NIH HHS/ -- U19 HD035476-10/HD/NICHD NIH HHS/ -- U24 MH081810/MH/NIMH NIH HHS/ -- U24 MH081810-01/MH/NIMH NIH HHS/ -- U24 MH081810-02/MH/NIMH NIH HHS/ -- U24 MH081810-03/MH/NIMH NIH HHS/ -- U24 MH081810-04/MH/NIMH NIH HHS/ -- U54 MH066673/MH/NIMH NIH HHS/ -- U54 MH066673-01A10001/MH/NIMH NIH HHS/ -- U54 MH066673-020001/MH/NIMH NIH HHS/ -- U54 MH066673-030001/MH/NIMH NIH HHS/ -- U54 MH066673-040001/MH/NIMH NIH HHS/ -- U54 MH066673-05/MH/NIMH NIH HHS/ -- U54 MH066673-050001/MH/NIMH NIH HHS/ -- UL1 RR024134/RR/NCRR NIH HHS/ -- UL1 RR024134-03/RR/NCRR NIH HHS/ -- UL1-RR024134-03/RR/NCRR NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2009 May 28;459(7246):569-73. doi: 10.1038/nature07953. Epub 2009 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19404257" target="_blank"〉PubMed〈/a〉

Description: Rotational spectra have traditionally been measured without a concurrent means of differentiating the molecular constituents of the sample. Here, we present an all-optical multipulse experiment that allows the correlated measurement of rotational and mass or photoelectron spectra by combining Fourier transform rotational coherence spectroscopy with resonance-enhanced multiphoton ionization. We demonstrate the power of this method with the determination of ground-state rotational constants and fragmentation channels for 10 different isotopes in a natural carbon disulfide sample. Three of the reported rotational constants were previously inaccessible by conventional spectroscopic techniques.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schroter, Christian -- Kosma, Kyriaki -- Schultz, Thomas -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):1011-5. doi: 10.1126/science.1204352. Epub 2011 Jul 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Born Institute, Max-Born-Strasse 2A, D-12489, Berlin-Adlershof, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21737701" target="_blank"〉PubMed〈/a〉

Description: We present experimental and theoretical evidence for an excited-state deactivation mechanism specific to hydrogen-bonded aromatic dimers, which may account, in part, for the photostability of the Watson-Crick base pairs in DNA. Femtosecond time-resolved mass spectroscopy of 2-aminopyridine clusters reveals an excited-state lifetime of 65 +/- 10 picoseconds for the near-planar hydrogen-bonded dimer, which is significantly shorter than the lifetime of either the monomer or the 3- and 4-membered nonplanar clusters. Ab initio calculations of reaction pathways and potential-energy profiles identify the mechanism of the enhanced excited-state decay of the dimer: Conical intersections connect the locally excited 1pipi* state and the electronic ground state with a 1pipi* charge-transfer state that is strongly stabilized by the transfer of a proton.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schultz, Thomas -- Samoylova, Elena -- Radloff, Wolfgang -- Hertel, Ingolf V -- Sobolewski, Andrzej L -- Domcke, Wolfgang -- New York, N.Y. -- Science. 2004 Dec 3;306(5702):1765-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Born Institute Berlin, Max-Born-Strasse 2a, D-10247 Berlin, Germany. schultz@mbi-berlin.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15576616" target="_blank"〉PubMed〈/a〉