Trades in complex Hadamard matrices

A trade in a complex Hadamard matrix is a set of entries which can be changed to obtain a different complex Hadamard matrix. We show that in a real Hadamard matrix of order $n$ all trades contain at least $n$ entries. We call a trade rectangular if it consists of a submatrix that can be multiplied by some scalar $c \neq 1$ to obtain another complex Hadamard matrix. We give a characterisation of rectangular trades in complex Hadamard matrices of order $n$ and show that they all contain at least $n$ entries. We conjecture that all trades in complex Hadamard matrices contain at least $n$ entries.Comment: 9 pages, no figure

Cloning and expression of a mammalian peptide chain release factor with sequence similarity to tryptophanyl-tRNA synthetases

The termination of protein synthesis is encoded by in-frame nonsense (stop) codons. Most organisms use three nonsense codons: UGA, UAG, and UAA. In contrast to sense codons, which are decoded by specific tRNAs, nonsense codons are decoded by proteins called release factors (RFs). Here we report the cloning of a mammalian RF cDNA by the use of monoclonal antibodies specific for rabbit RF. Functional studies showed that, when expressed in Escherichia coli, the protein encoded by this cDNA has in vitro biochemical characteristics similar to those of previously characterized mammalian RFs. DNA sequencing of this eukaryotic RF cDNA revealed a remarkable sequence similarity to bacterial and mitochondrial tryptophanyl-tRNA synthetases, with the greatest similarity confined to the synthetase active site, and no obvious similarity to bacterial RFs

Exotic complex Hadamard matrices, and their equivalence

In this paper we use a design theoretical approach to construct new, previously unknown complex Hadamard matrices. Our methods generalize and extend the earlier results of de la Harpe--Jones and Munemasa--Watatani and offer a theoretical explanation for the existence of some sporadic examples of complex Hadamard matrices in the existing literature. As it is increasingly difficult to distinguish inequivalent matrices from each other, we propose a new invariant, the fingerprint of complex Hadamard matrices. As a side result, we refute a conjecture of Koukouvinos et al. on (n-8)x(n-8) minors of real Hadamard matrices.Comment: 10 pages. To appear in Cryptography and Communications: Discrete Structures, Boolean Functions and Sequence

On quaternary complex Hadamard matrices of small orders

One of the main goals of design theory is to classify, characterize and count various combinatorial objects with some prescribed properties. In most cases, however, one quickly encounters a combinatorial explosion and even if the complete enumeration of the objects is possible, there is no apparent way how to study them in details, store them efficiently, or generate a particular one rapidly. In this paper we propose a novel method to deal with these difficulties, and illustrate it by presenting the classification of quaternary complex Hadamard matrices up to order 8. The obtained matrices are members of only a handful of parametric families, and each inequivalent matrix, up to transposition, can be identified through its fingerprint.Comment: 7 page

Correction: Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes (PLoS ONE (2010) 5:12 (e15687) DOI: 10.1371/journal.pone.0015687)

The middle initial of the third author is missing. The third author’s complete name is: Ayman W. El-Hattab. The correct citation is: Sadikovic B, Wang J, El-Hattab AW, Landsverk M, Douglas G, Brundage EK, et al. (2010) Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes. PLoS ONE 5(12): e15687. https://doi.org/10.1371/journal.pone.0015687

The GABA Transaminase, ABAT, Is Essential for Mitochondrial Nucleoside Metabolism

SummaryABAT is a key enzyme responsible for catabolism of principal inhibitory neurotransmitter γ-aminobutyric acid (GABA). We report an essential role for ABAT in a seemingly unrelated pathway, mitochondrial nucleoside salvage, and demonstrate that mutations in this enzyme cause an autosomal recessive neurometabolic disorder and mtDNA depletion syndrome (MDS). We describe a family with encephalomyopathic MDS caused by a homozygous missense mutation in ABAT that results in elevated GABA in subjects’ brains as well as decreased mtDNA levels in subjects’ fibroblasts. Nucleoside rescue and co-IP experiments pinpoint that ABAT functions in the mitochondrial nucleoside salvage pathway to facilitate conversion of dNDPs to dNTPs. Pharmacological inhibition of ABAT through the irreversible inhibitor Vigabatrin caused depletion of mtDNA in photoreceptor cells that was prevented through addition of dNTPs in cell culture media. This work reveals ABAT as a connection between GABA metabolism and nucleoside metabolism and defines a neurometabolic disorder that includes MDS

Functional analysis of the SRV-1 RNA frameshifting pseudoknot

Simian retrovirus type-1 uses programmed ribosomal frameshifting to control expression of the Gag-Pol polyprotein from overlapping gag and pol open-reading frames. The frameshifting signal consists of a heptanucleotide slippery sequence and a downstream-located 12-base pair pseudoknot. The solution structure of this pseudoknot, previously solved by NMR [Michiels,P.J., Versleijen,A.A., Verlaan,P.W., Pleij,C.W., Hilbers,C.W. and Heus,H.A. (2001) Solution structure of the pseudoknot of SRV-1 RNA, involved in ribosomal frameshifting. J. Mol. Biol., 310, 1109–1123] has a classical H-type fold and forms an extended triple helix by interactions between loop 2 and the minor groove of stem 1 involving base–base and base–sugar contacts. A mutational analysis was performed to test the functional importance of the triple helix for −1 frameshifting in vitro. Changing bases in L2 or base pairs in S1 involved in a base triple resulted in a 2- to 5-fold decrease in frameshifting efficiency. Alterations in the length of L2 had adverse effects on frameshifting. The in vitro effects were well reproduced in vivo, although the effect of enlarging L2 was more dramatic in vivo. The putative role of refolding kinetics of frameshifter pseudoknots is discussed. Overall, the data emphasize the role of the triple helix in −1 frameshifting

YY1 haploinsufficiency causes an intellectual disability syndrome featuring transcriptional and chromatin dysfunction

Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and as an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from affected individuals' cells with antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators.Michele Gabriele, Anneke T. Vulto-van Silfhout, Pierre-Luc Germain, Alessandro Vitriolo, Raman Kumar, Evelyn Douglas, Eric Haan, Kenjiro Kosaki, Toshiki Takenouchi, Anita Rauch, Katharina Steindl, Eirik Frengen, Doriana Misceo, Christeen Ramane J. Pedurupillay, Petter Stromme, Jill A. Rosenfeld, Yunru Shao, William J. Craigen, Christian P. Schaaf, David Rodriguez-Buritica, Laura Farach, Jennifer Friedman, Perla Thulin, Scott D. McLean, Kimberly M. Nugent, Jenny Morton, Jillian Nicholl, Joris Andrieux, Asbjørg Stray-Pedersen, Pascal Chambon, Sophie Patrier, Sally A. Lynch, Susanne Kjaergaard, Pernille M. Tørring, Charlotte Brasch-Andersen, Anne Ronan, Arie van Haeringen, Peter J. Anderson, Zöe Powis, Han G. Brunner, Rolph Pfundt, Janneke H.M. Schuurs-Hoeijmakers, Bregje W.M. van Bon, Stefan Lelieveld, Christian Gilissen, Willy M. Nillesen, Lisenka E.L.M. Vissers, Jozef Gecz, David A. Koolen, Giuseppe Testa, Bert B.A. de Vrie

SNP genotyping to screen for a common deletion in CHARGE Syndrome

BACKGROUND: CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR) markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients. METHODS: We have extended our previous study by employing a much higher density of SNP markers (3258) with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs. RESULTS: A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD) was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size. CONCLUSIONS: The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb

Aberrant function of the C-terminal tail of HIST1H1E Aacelerates cellular senescence and causes premature aging

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging