ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

11

Unknown

Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits (2013)

U. Styrkarsdottir ; G. Thorleifsson ; P. Sulem ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 497(7450): 517-20. doi: 10.1038/nature12124.

add to mindlist on the mindlist

Details

Publication Date: 2013-05-07

Description: Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic individuals, we found a rare nonsense mutation within the leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C〉T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C〉T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C〉T mutation overlaps that of Lgr4 mutant mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Styrkarsdottir, Unnur -- Thorleifsson, Gudmar -- Sulem, Patrick -- Gudbjartsson, Daniel F -- Sigurdsson, Asgeir -- Jonasdottir, Aslaug -- Jonasdottir, Adalbjorg -- Oddsson, Asmundur -- Helgason, Agnar -- Magnusson, Olafur T -- Walters, G Bragi -- Frigge, Michael L -- Helgadottir, Hafdis T -- Johannsdottir, Hrefna -- Bergsteinsdottir, Kristin -- Ogmundsdottir, Margret H -- Center, Jacqueline R -- Nguyen, Tuan V -- Eisman, John A -- Christiansen, Claus -- Steingrimsson, Erikur -- Jonasson, Jon G -- Tryggvadottir, Laufey -- Eyjolfsson, Gudmundur I -- Theodors, Asgeir -- Jonsson, Thorvaldur -- Ingvarsson, Thorvaldur -- Olafsson, Isleifur -- Rafnar, Thorunn -- Kong, Augustine -- Sigurdsson, Gunnar -- Masson, Gisli -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- HL-102923/HL/NHLBI NIH HHS/ -- HL-102924/HL/NHLBI NIH HHS/ -- HL-102925/HL/NHLBI NIH HHS/ -- HL-102926/HL/NHLBI NIH HHS/ -- HL-103010/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 May 23;497(7450):517-20. doi: 10.1038/nature12124. Epub 2013 May 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE Genetics/Amgen, 101 Reykjavik, Iceland. unnurth@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23644456" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Australia ; Biliary Tract Neoplasms/*genetics ; Bone Density/*genetics ; Carcinoma, Squamous Cell/*genetics ; Codon, Nonsense/*genetics ; Denmark ; Down-Regulation/genetics ; Female ; Heterozygote ; Humans ; Iceland ; Male ; Menarche/genetics ; Mice ; Mice, Knockout ; Osteoporotic Fractures/*genetics ; Phenotype ; Receptors, G-Protein-Coupled/chemistry/deficiency/*genetics/metabolism ; Skin Neoplasms/*genetics ; Testosterone/analysis ; Water-Electrolyte Imbalance/*genetics

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

12

Unknown

Sequence variants in the RNF212 gene associate with genome-wide recombination rate (2008)

A. Kong ; G. Thorleifsson ; H. Stefansson ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 319(5868): 1398-401. doi: 10.1126/science.1152422.

add to mindlist on the mindlist

Details

Publication Date: 2008-02-02

Description: The genome-wide recombination rate varies between individuals, but the mechanism controlling this variation in humans has remained elusive. A genome-wide search identified sequence variants in the 4p16.3 region correlated with recombination rate in both males and females. These variants are located in the RNF212 gene, a putative ortholog of the ZHP-3 gene that is essential for recombinations and chiasma formation in Caenorhabditis elegans. It is noteworthy that the haplotype formed by two single-nucleotide polymorphisms (SNPs) associated with the highest recombination rate in males is associated with a low recombination rate in females. Consequently, if the frequency of the haplotype changes, the average recombination rate will increase for one sex and decrease for the other, but the sex-averaged recombination rate of the population can stay relatively constant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kong, Augustine -- Thorleifsson, Gudmar -- Stefansson, Hreinn -- Masson, Gisli -- Helgason, Agnar -- Gudbjartsson, Daniel F -- Jonsdottir, Gudrun M -- Gudjonsson, Sigurjon A -- Sverrisson, Sverrir -- Thorlacius, Theodora -- Jonasdottir, Aslaug -- Hardarson, Gudmundur A -- Palsson, Stefan T -- Frigge, Michael L -- Gulcher, Jeffrey R -- Thorsteinsdottir, Unnur -- Stefansson, Kari -- New York, N.Y. -- Science. 2008 Mar 7;319(5868):1398-401. doi: 10.1126/science.1152422. Epub 2008 Jan 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉deCODE Genetics Inc, 101 Reykjavik, Iceland. kong@decode.is〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18239089" target="_blank"〉PubMed〈/a〉

Keywords: Alleles ; Chromosomes, Human, Pair 4/*genetics ; Fathers ; Female ; *Genome, Human ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Meiosis ; Molecular Sequence Data ; Mothers ; Polymorphism, Single Nucleotide ; *Recombination, Genetic ; Sex Characteristics ; Synaptonemal Complex/metabolism ; Ubiquitin-Protein Ligases/*genetics

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

13

Unknown

ORGANIC CHEMISTRY. Lewis acids turn unreactive substrates into pure enantiomers (2016)

A. Dumoulin ; G. Masson

American Association for the Advancement of Science (AAAS)

In: Science. 351(6276): 918-9. doi: 10.1126/science.aaf2577.

add to mindlist on the mindlist

Details

Publication Date: 2016-02-27

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dumoulin, Audrey -- Masson, Geraldine -- New York, N.Y. -- Science. 2016 Feb 26;351(6276):918-9. doi: 10.1126/science.aaf2577.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Universite Paris-Sud, Universite Paris-Saclay, Gif-sur-Yvette, France. ; Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Universite Paris-Sud, Universite Paris-Saclay, Gif-sur-Yvette, France. geraldine.masson@cnrs.fr.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917754" target="_blank"〉PubMed〈/a〉

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

14

Unknown

Seismic evidence for shallow gas-escape features associated with a retreating gas hydrate zone offshore west Svalbard (2012)

Sudipta Sarkar, Christian Berndt, Timothy A. Minshull, Graham K. Westbrook, Dirk Klaeschen, Douglas G. Masson, Anne Chabert and Kate E. Thatcher

Wiley

In: Journal of Geophysical Research JGR - Solid Earth

add to mindlist on the mindlist

Details

Publication Date: 2012-09-19

Description: Active gas venting occurs on the uppermost continental slope off west Svalbard, close to and upslope from the present-day intersection of the base of methane hydrate stability (BMHS) with the seabed in about 400 m water depth in the inter-fan region between the Kongsfjorden and Isfjorden cross-shelf troughs. From an integrated analysis of high-resolution, two-dimensional, pre-stack migrated seismic reflection profiles and multibeam bathymetric data, we map out a bottom simulating reflector (BSR) in the inter-fan region and analyze the subsurface gas migration and accumulation. Gas seeps mostly occur in the zone from which the BMHS at the seabed has retreated over the recent past (1975–2008) as a consequence of a bottom water temperature rise of 1°C. The overall margin-parallel alignment of the gas seeps is not related to fault-controlled gas migration, as seismic evidence of faults is absent. There is no evidence for a BSR close to the gas flare region in the upper slope but numerous gas pockets exist directly below the predicted BMHS. While the contour following trend of the gas seeps could be a consequence of retreat of the landward limit of the BMHS and gas hydrate dissociation, the scattered distribution of seeps within the probable hydrate dissociation corridor and the occurrence of a cluster of seeps outside the predicted BMHS limit and near the shelf break indicate the role of lithological heterogeneity in focusing gas migration.

Print ISSN: 0148-0227

Topics: Geosciences , Physics

Published by Wiley on behalf of American Geophysical Union (AGU).

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

15

Unknown

PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks (2012)

Krietsch, J., Caron, M.-C., Gagne, J.-P., Ethier, C., Vignard, J., Vincent, M., Rouleau, M., Hendzel, M. J., Poirier, G. G., Masson, J.-Y.

Oxford University Press

In: Nucleic Acids Research

add to mindlist on the mindlist

Details

Publication Date: 2012-11-04

Description: After the generation of DNA double-strand breaks (DSBs), poly(ADP-ribose) polymerase-1 (PARP-1) is one of the first proteins to be recruited and activated through its binding to the free DNA ends. Upon activation, PARP-1 uses NAD + to generate large amounts of poly(ADP-ribose) (PAR), which facilitates the recruitment of DNA repair factors. Here, we identify the RNA-binding protein NONO, a partner protein of SFPQ, as a novel PAR-binding protein. The protein motif being primarily responsible for PAR-binding is the RNA recognition motif 1 (RRM1), which is also crucial for RNA-binding, highlighting a competition between RNA and PAR as they share the same binding site. Strikingly, the in vivo recruitment of NONO to DNA damage sites completely depends on PAR, generated by activated PARP-1. Furthermore, we show that upon PAR-dependent recruitment, NONO stimulates nonhomologous end joining (NHEJ) and represses homologous recombination (HR) in vivo . Our results therefore place NONO after PARP activation in the context of DNA DSB repair pathway decision. Understanding the mechanism of action of proteins that act in the same pathway as PARP-1 is crucial to shed more light onto the effect of interference on PAR-mediated pathways with PARP inhibitors, which have already reached phase III clinical trials but are until date poorly understood.

Print ISSN: 0305-1048

Electronic ISSN: 1362-4962

Topics: Biology

Published by Oxford University Press

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

PAPER CURRENT

S·F·X

Fulltext

16

Unknown

Subaqueous sediment density flows: Depositional processes and deposit types (2012)

PETER J. TALLING, DOUGLAS G. MASSON, ESTHER J. SUMNER, GIUSEPPE MALGESINI

Wiley

In: Sedimentology

add to mindlist on the mindlist

Details

Publication Date: 2012-10-31

Description: Submarine sediment density flows are one of the most important processes for moving sediment across our planet, yet they are extremely difficult to monitor directly. The speed of long run-out submarine density flows has been measured directly in just five locations worldwide and their sediment concentration has never been measured directly. The only record of most density flows is their sediment deposit. This article summarizes the processes by which density flows deposit sediment and proposes a new single classification for the resulting types of deposit. Colloidal properties of fine cohesive mud ensure that mud deposition is complex, and large volumes of mud can sometimes pond or drain-back for long distances into basinal lows. Deposition of ungraded mud (T E-3 ) most probably finally results from en masse consolidation in relatively thin and dense flows, although initial size sorting of mud indicates earlier stages of dilute and expanded flow. Graded mud (T E-2 ) and finely laminated mud (T E-1 ) most probably result from floc settling at lower mud concentrations. Grain-size breaks beneath mud intervals are commonplace, and record bypass of intermediate grain sizes due to colloidal mud behaviour. Planar-laminated (T D ) and ripple cross-laminated (T C ) non-cohesive silt or fine sand is deposited by dilute flow, and the external deposit shape is consistent with previous models of spatial decelerating (dissipative) dilute flow. A grain-size break beneath the ripple cross-laminated (T C ) interval is common, and records a period of sediment reworking (sometimes into dunes) or bypass. Finely planar-laminated sand can be deposited by low-amplitude bed waves in dilute flow (T B-1 ), but it is most likely to be deposited mainly by high-concentration near-bed layers beneath high-density flows (T B-2 ). More widely spaced planar lamination (T B-3 ) occurs beneath massive clean sand (T A ), and is also formed by high-density turbidity currents. High-density turbidite deposits (T A , T B-2 and T B-3 ) have a tabular shape consistent with hindered settling, and are typically overlain by a more extensive drape of low-density turbidite (T D and T C ,). This core and drape shape suggests that events sometimes comprise two distinct flow components. Massive clean sand is less commonly deposited en masse by liquefied debris flow (D CS ), in which case the clean sand is ungraded or has a patchy grain-size texture. Clean-sand debrites can extend for several tens of kilometres before pinching out abruptly. Up-current transitions suggest that clean-sand debris flows sometimes form via transformation from high-density turbidity currents. Cohesive debris flows can deposit three types of ungraded muddy sand that may contain clasts. Thick cohesive debrites tend to occur in more proximal settings and extend from an initial slope failure. Thinner and highly mobile low-strength cohesive debris flows produce extensive deposits restricted to distal areas. These low-strength debris flows may contain clasts and travel long distances (D M-2 ), or result from more local flow transformation due to turbulence damping by cohesive mud (D M-1 ). Mapping of individual flow deposits (beds) emphasizes how a single event can contain several flow types, with transformations between flow types. Flow transformation may be from dilute to dense flow, as well as from dense to dilute flow. Flow state, deposit type and flow transformation are strongly dependent on the volume fraction of cohesive fine mud within a flow. Recent field observations show significant deviations from previous widely cited models, and many hypotheses linking flow type to deposit type are poorly tested. There is much still to learn about these remarkable flows.

Print ISSN: 0037-0746

Electronic ISSN: 1365-3091

Topics: Geosciences

Published by Wiley

Permalink