2,160 research outputs found
Slx5/Slx8-dependent ubiquitin hotspots on chromatin contribute to stress tolerance
Chromatin is a highly regulated environment, and protein association with chromatin is often controlled by post-translational modifications and the corresponding enzymatic machinery. Specifically, SUMO-targeted ubiquitin ligases (STUbLs) have emerged as key players in nuclear quality control, genome maintenance, and transcription. However, how STUbLs select specific substrates among myriads of SUMOylated proteins on chromatin remains unclear. Here, we reveal a remarkable co-localization of the budding yeast STUbL Slx5/Slx8 and ubiquitin at seven genomic loci that we term "ubiquitin hotspots". Ubiquitylation at these sites depends on Slx5/Slx8 and protein turnover on the Cdc48 segregase. We identify the transcription factor-like Ymr111c/Euc1 to associate with these sites and to be a critical determinant of ubiquitylation. Euc1 specifically targets Slx5/Slx8 to ubiquitin hotspots via bipartite binding of Slx5 that involves the Slx5 SUMO-interacting motifs and an additional, novel substrate recognition domain. Interestingly, the Euc1-ubiquitin hotspot pathway acts redundantly with chromatin modifiers of the H2A.Z and Rpd3L pathways in specific stress responses. Thus, our data suggest that STUbL-dependent ubiquitin hotspots shape chromatin during stress adaptation
The Rostock Energetic Feed Evaluation on the Base of Net Energy
Feed evaluation was an emphasis of research from the foundation of the Oskar-Kellner-Institute of Animal Nutrition in 1953 at Rostock by Prof. Kurt Nehring. The aim of the research work was the elaboration of a feed evaluation system containing reference numbers of feed values and requirements of farm animals. The approach and the present system are outlined in this paper
The INO80 Complex Removes H2A.Z to Promote Presynaptic Filament Formation during Homologous Recombination
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR-DNA end resection and presynaptic filament formation. Importantly, the second function is linked to the histone variant H2A.Z. In the absence of H2A.Z, presynaptic filament formation and HR are restored in INO80-C-deficient mutants, suggesting that presynaptic filament formation is the crucial INO80-C function during HR
Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions
Loss of the lysosomal ClC-7/Ostm1 2Cl(-)/H(+) exchanger causes lysosomal storage disease and osteopetrosis in humans and additionally changes fur colour in mice. Its conversion into a Cl(-) conductance in Clcn7(unc/unc) mice entails similarly severe lysosomal storage, but less severe osteopetrosis and no change in fur colour. To elucidate the basis for these phenotypical differences, we generated Clcn7(td/td) mice expressing an ion transport-deficient mutant. Their osteopetrosis was as severe as in Clcn7(-/-) mice, suggesting that the electric shunt provided by ClC-7(unc) can partially rescue osteoclast function. The normal coat colour of Clcn7(td/td) mice and their less severe neurodegeneration suggested that the ClC-7 protein, even when lacking measurable ion transport activity, is sufficient for hair pigmentation and that the conductance of ClC-7(unc) is harmful for neurons. Our in vivo structure-function analysis of ClC-7 reveals that both protein-protein interactions and ion transport must be considered in the pathogenesis of ClC-7-related diseases
Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels
In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that besides the osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine. HEK293 cells engineered to express defined subsets of LRRC8 isoforms were used to elucidate the subunit-dependence of transport. Whereas LRRC8D was crucial for the translocation of overall neutral compounds like myo-inositol, taurine and GABA and sustained the transport of positively charged lysine, flux of negatively charged aspartate was equally well supported by LRRC8E. Disruption of LRRC8B or LRRC8C failed to decrease transport rates of all investigated substrates, but their inclusion into LRRC8 heteromers influenced VRAC's substrate preference. This suggested that individual VRACs can contain three or more different LRRC8 subunits, a conclusion confirmed by sequential co-immunoprecipitations. Our work suggests a composition-dependent role of VRACs in extracellular signal transduction
Gauss sum factorization with cold atoms
We report the first implementation of a Gauss sum factorization algorithm by
an internal state Ramsey interferometer using cold atoms. A sequence of
appropriately designed light pulses interacts with an ensemble of cold rubidium
atoms. The final population in the involved atomic levels determines a Gauss
sum. With this technique we factor the number N=263193.Comment: 4 pages, 5 figure
Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels
Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated chloride channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying anion channel PAORAC/ASOR. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR's pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR's role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed
ΠΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠΈ ΠΈΠΌΠΏΠ»Π°Π½ΡΠΎΠ² ΠΎΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠΌΠΈ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ
Π Π°Π±ΠΎΡΠ° Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π° Π½Π° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ Π°Π΄Π΄ΠΈΡΠΈΠ²Π½ΠΎ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΡΠΊΡΡΡΠΎΠ»Π΄ΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠΈΡΠ°Π½ΠΎΠ²ΠΎΠ³ΠΎ ΡΠΏΠ»Π°Π²Π° Ti6Al4V Ρ Π°ΡΠ΅Π½Π΅Π΄ΠΈΠ°Π·ΠΎΠ½ΠΈΠ΅Π²ΡΠΌΠΈ ΡΠΎΠ·ΠΈΠ»Π°ΡΠ°ΠΌΠΈ ΠΈ ΠΌΠ΅ΡΠ°Π»Π»-ΠΎΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΊΠ°ΡΠΊΠ°ΡΠ°ΠΌΠΈ Π΄Π»Ρ ΡΠ»ΡΡΡΠ΅Π½ΠΈΡ Π±ΠΈΠΎΡΠΎΠ²ΠΌΠ΅ΡΡΠΈΠΌΠΎΡΡΠΈ ΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΠΎΡΡΠ΅ΠΎΠΈΠ½ΡΠ΅Π³ΡΠ°ΡΠΈΠΈ. Π¦Π΅Π»ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΊΠΎΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΠΉ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠ΅ΠΉ ΡΠΊΡΡΡΠΎΠ»Π΄ΠΎΠ² Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΡΠ΅Π½Π΄ΠΈΠ°Π·ΠΎΠ½ΠΈΠΉ ΡΠΎΠ·ΠΈΠ»Π°ΡΠΎΠ² ΠΈ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠΎΡΠ³Π°Π½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠ°ΡΠΊΠ°ΡΠΎΠ² Π΄Π»Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΠΈ ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΠΎΠ² Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°.The work is aimed at developing a surface modification of additively obtained scaffolds based on a Ti6Al4V titanium alloy with arenediazonium tosylates and metal-organic frameworks to improve biocompatibility and osseointegration. Aim of research to develop methods for covalent modification of scaffold surfaces using arenediazonium tosylates and metal-organic frameworks for better implant survival in the human body
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