Статті в журналах: "Nse4"

1

Kolesar, Peter, Karel Stejskal, David Potesil, Johanne M. Murray, and Jan J. Palecek. "Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase." Cells 11, no. 1 (January 4, 2022): 165. http://dx.doi.org/10.3390/cells11010165.

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Structural Maintenance of Chromosomes (SMC) complexes are important for many aspects of the chromosomal organization. Unlike cohesin and condensin, the SMC5/6 complex contains a variant RING domain carried by its Nse1 subunit. RING domains are characteristic for ubiquitin ligases, and human NSE1 has been shown to possess ubiquitin-ligase activity in vitro. However, other studies were unable to show such activity. Here, we confirm Nse1 ubiquitin-ligase activity using purified Schizosaccharomyces pombe proteins. We demonstrate that the Nse1 ligase activity is stimulated by Nse3 and Nse4. We show that Nse1 specifically utilizes Ubc13/Mms2 E2 enzyme and interacts directly with ubiquitin. We identify the Nse1 mutation (R188E) that specifically disrupts its E3 activity and demonstrate that the Nse1-dependent ubiquitination is particularly important under replication stress. Moreover, we determine Nse4 (lysine K181) as the first known SMC5/6-associated Nse1 substrate. Interestingly, abolition of Nse4 modification at K181 leads to suppression of DNA-damage sensitivity of other SMC5/6 mutants. Altogether, this study brings new evidence for Nse1 ubiquitin ligase activity, significantly advancing our understanding of this enigmatic SMC5/6 function.

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2

Pebernard, Stephanie, J. Jefferson P. Perry, John A. Tainer, and Michael N. Boddy. "Nse1 RING-like Domain Supports Functions of the Smc5-Smc6 Holocomplex in Genome Stability." Molecular Biology of the Cell 19, no. 10 (October 2008): 4099–109. http://dx.doi.org/10.1091/mbc.e08-02-0226.

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The Smc5-Smc6 holocomplex plays essential but largely enigmatic roles in chromosome segregation, and facilitates DNA repair. The Smc5-Smc6 complex contains six conserved non-SMC subunits. One of these, Nse1, contains a RING-like motif that often confers ubiquitin E3 ligase activity. We have functionally characterized the Nse1 RING-like motif, to determine its contribution to the chromosome segregation and DNA repair roles of Smc5-Smc6. Strikingly, whereas a full deletion of nse1 is lethal, the Nse1 RING-like motif is not essential for cellular viability. However, Nse1 RING mutant cells are hypersensitive to a broad spectrum of genotoxic stresses, indicating that the Nse1 RING motif promotes DNA repair functions of Smc5-Smc6. We tested the ability of both human and yeast Nse1 to mediate ubiquitin E3 ligase activity in vitro and found no detectable activity associated with full-length Nse1 or the isolated RING domains. Interestingly, however, the Nse1 RING-like domain is required for normal Nse1-Nse3-Nse4 trimer formation in vitro and for damage-induced recruitment of Nse4 and Smc5 to subnuclear foci in vivo. Thus, we propose that the Nse1 RING-like motif is a protein–protein interaction domain required for Smc5-Smc6 holocomplex integrity and recruitment to, or retention at, DNA lesions.

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3

Jo, Aera, Shibai Li, Jin Woo Shin, Xiaolan Zhao, and Yunje Cho. "Structure Basis for Shaping the Nse4 Protein by the Nse1 and Nse3 Dimer within the Smc5/6 Complex." Journal of Molecular Biology 433, no. 9 (April 2021): 166910. http://dx.doi.org/10.1016/j.jmb.2021.166910.

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4

Guerineau, Marc, Zdenek Kriz, Lucie Kozakova, Katerina Bednarova, Pavel Janos, and Jan Palecek. "Analysis of the Nse3/MAGE-Binding Domain of the Nse4/EID Family Proteins." PLoS ONE 7, no. 4 (April 20, 2012): e35813. http://dx.doi.org/10.1371/journal.pone.0035813.

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5

Pebernard, Stephanie, W. Hayes McDonald, Yelena Pavlova, John R. Yates, and Michael N. Boddy. "Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis." Molecular Biology of the Cell 15, no. 11 (November 2004): 4866–76. http://dx.doi.org/10.1091/mbc.e04-05-0436.

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The structural maintenance of chromosomes (SMC) family of proteins play key roles in the organization, packaging, and repair of chromosomes. Cohesin (Smc1+3) holds replicated sister chromatids together until mitosis, condensin (Smc2+4) acts in chromosome condensation, and Smc5+6 performs currently enigmatic roles in DNA repair and chromatin structure. The SMC heterodimers must associate with non-SMC subunits to perform their functions. Using both biochemical and genetic methods, we have isolated a novel subunit of the Smc5+6 complex, Nse3. Nse3 is an essential nuclear protein that is required for normal mitotic chromosome segregation and cellular resistance to a number of genotoxic agents. Epistasis with Rhp51 (Rad51) suggests that like Smc5+6, Nse3 functions in the homologous recombination based repair of DNA damage. We previously identified two non-SMC subunits of Smc5+6 called Nse1 and Nse2. Analysis of nse1-1, nse2-1, and nse3-1 mutants demonstrates that they are crucial for meiosis. The Nse1 mutant displays meiotic DNA segregation and homologous recombination defects. Spore viability is reduced by nse2-1 and nse3-1, without affecting interhomolog recombination. Finally, genetic interactions shared by the nse mutants suggest that the Smc5+6 complex is important for replication fork stability.

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6

Taniura, Hideo, Naoya Tanabe, Yumi Bando, and Natsumi Arai. "Nse1 and Nse4, subunits of the Smc5–Smc6 complex, are involved in Dictyostelium development upon starvation." Development, Growth & Differentiation 57, no. 6 (June 2, 2015): 430–43. http://dx.doi.org/10.1111/dgd.12223.

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7

Hudson, Jessica J. R., Katerina Bednarova, Lucie Kozakova, Chunyan Liao, Marc Guerineau, Rita Colnaghi, Susanne Vidot, et al. "Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families." PLoS ONE 6, no. 2 (February 25, 2011): e17270. http://dx.doi.org/10.1371/journal.pone.0017270.

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8

Hu, Bin, Chunyan Liao, Stefan H. Millson, Mehdi Mollapour, Chrisostomos Prodromou, Laurence H. Pearl, Peter W. Piper, and Barry Panaretou. "Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex." Molecular Microbiology 55, no. 6 (February 7, 2005): 1735–50. http://dx.doi.org/10.1111/j.1365-2958.2005.04531.x.

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9

Andrews, Emily A., Jan Palecek, John Sergeant, Elaine Taylor, Alan R. Lehmann, and Felicity Z. Watts. "Nse2, a Component of the Smc5-6 Complex, Is a SUMO Ligase Required for the Response to DNA Damage." Molecular and Cellular Biology 25, no. 1 (January 1, 2005): 185–96. http://dx.doi.org/10.1128/mcb.25.1.185-196.2005.

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ABSTRACT The Schizosaccharomyces pombe SMC proteins Rad18 (Smc6) and Spr18 (Smc5) exist in a high-M r complex which also contains the non-SMC proteins Nse1, Nse2, Nse3, and Rad62. The Smc5-6 complex, which is essential for viability, is required for several aspects of DNA metabolism, including recombinational repair and maintenance of the DNA damage checkpoint. We have characterized Nse2 and show here that it is a SUMO ligase. Smc6 (Rad18) and Nse3, but not Smc5 (Spr18) or Nse1, are sumoylated in vitro in an Nse2-dependent manner, and Nse2 is itself autosumoylated, predominantly on the C-terminal part of the protein. Mutations of C195 and H197 in the Nse2 RING-finger-like motif abolish Nse2-dependent sumoylation. nse2.SA mutant cells, in which nse2.C195S-H197A is integrated as the sole copy of nse2, are viable, whereas the deletion of nse2 is lethal. Smc6 (Rad18) is sumoylated in vivo: the sumoylation level is increased upon exposure to DNA damage and is drastically reduced in the nse2.SA strain. Since nse2.SA cells are sensitive to DNA-damaging agents and to exposure to hydroxyurea, this implicates the Nse2-dependent sumoylation activity in DNA damage responses but not in the essential function of the Smc5-6 complex.

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10

Sergeant, John, Elaine Taylor, Jan Palecek, Maria Fousteri, Emily A. Andrews, Sara Sweeney, Hideo Shinagawa, Felicity Z. Watts, and Alan R. Lehmann. "Composition and Architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) Complex." Molecular and Cellular Biology 25, no. 1 (January 1, 2005): 172–84. http://dx.doi.org/10.1128/mcb.25.1.172-184.2005.

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ABSTRACT The rad18 gene of Schizosaccharomyces pombe is an essential gene that is involved in several different DNA repair processes. Rad18 (Smc6) is a member of the structural maintenance of chromosomes (SMC) family and, together with its SMC partner Spr18 (Smc5), forms the core of a high-molecular-weight complex. We show here that both S. pombe and human Smc5 and -6 interact through their hinge domains and that four independent temperature-sensitive mutants of Rad18 (Smc6) are all mutated at the same glycine residue in the hinge region. This mutation abolishes the interactions between the hinge regions of Rad18 (Smc6) and Spr18 (Smc5), as does mutation of a conserved glycine in the hinge region of Spr18 (Smc5). We purified the Smc5-6 complex from S. pombe and identified four non-SMC components, Nse1, Nse2, Nse3, and Rad62. Nse3 is a novel protein which is related to the mammalian MAGE protein family, many members of which are specifically expressed in cancer tissue. In initial steps to understand the architecture of the complex, we identified two subcomplexes containing Rad18-Spr18-Nse2 and Nse1-Nse3-Rad62. The subcomplexes are probably bridged by a weaker interaction between Nse2 and Nse3.

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11

Yu, You, Shibai Li, Zheng Ser, Tanmoy Sanyal, Koyi Choi, Bingbing Wan, Huihui Kuang, et al. "Integrative analysis reveals unique structural and functional features of the Smc5/6 complex." Proceedings of the National Academy of Sciences 118, no. 19 (May 3, 2021): e2026844118. http://dx.doi.org/10.1073/pnas.2026844118.

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Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits.

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12

Zhang, Junya, Robert C. Augustine, Masaharu Suzuki, Juanjuan Feng, Si Nian Char, Bing Yang, Donald R. McCarty, and Richard D. Vierstra. "The SUMO ligase MMS21 profoundly influences maize development through its impact on genome activity and stability." PLOS Genetics 17, no. 10 (October 25, 2021): e1009830. http://dx.doi.org/10.1371/journal.pgen.1009830.

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The post-translational addition of SUMO plays essential roles in numerous eukaryotic processes including cell division, transcription, chromatin organization, DNA repair, and stress defense through its selective conjugation to numerous targets. One prominent plant SUMO ligase is METHYL METHANESULFONATE-SENSITIVE (MMS)-21/HIGH-PLOIDY (HPY)-2/NON-SMC-ELEMENT (NSE)-2, which has been connected genetically to development and endoreduplication. Here, we describe the potential functions of MMS21 through a collection of UniformMu and CRISPR/Cas9 mutants in maize (Zea mays) that display either seed lethality or substantially compromised pollen germination and seed/vegetative development. RNA-seq analyses of leaves, embryos, and endosperm from mms21 plants revealed a substantial dysregulation of the maize transcriptome, including the ectopic expression of seed storage protein mRNAs in leaves and altered accumulation of mRNAs associated with DNA repair and chromatin dynamics. Interaction studies demonstrated that MMS21 associates in the nucleus with the NSE4 and STRUCTURAL MAINTENANCE OF CHROMOSOMES (SMC)-5 components of the chromatin organizer SMC5/6 complex, with in vitro assays confirming that MMS21 will SUMOylate SMC5. Comet assays measuring genome integrity, sensitivity to DNA-damaging agents, and protein versus mRNA abundance comparisons implicated MMS21 in chromatin stability and transcriptional controls on proteome balance. Taken together, we propose that MMS21-directed SUMOylation of the SMC5/6 complex and other targets enables proper gene expression by influencing chromatin structure.

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13

Aragón, Luis. "The Smc5/6 Complex: New and Old Functions of the Enigmatic Long-Distance Relative." Annual Review of Genetics 52, no. 1 (November 23, 2018): 89–107. http://dx.doi.org/10.1146/annurev-genet-120417-031353.

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Smc5 and Smc6, together with the kleisin Nse4, form the heart of the enigmatic and poorly understood Smc5/6 complex, which is frequently viewed as a cousin of cohesin and condensin with functions in DNA repair. As novel functions for cohesin and condensin complexes in the organization of long-range chromatin architecture have recently emerged, new unsuspected roles for Smc5/6 have also surfaced. Here, I aim to provide a comprehensive overview of our current knowledge of the Smc5/6 complex, including its long-established function in genome stability, its multiple roles in DNA repair, and its recently discovered connection to the transcription inhibition of hepatitis B virus genomes. In addition, I summarize new research that is beginning to tease out the molecular details of Smc5/6 structure and function, knowledge that will illuminate the nuclear activities of Smc5/6 in the stability and dynamics of eukaryotic genomes.

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14

Odiba, Arome Solomon, Chiemekam Samuel Ezechukwu, Guiyan Liao, Siqiao Li, Zhongliang Chen, Xihui Liu, Wenxia Fang, Cheng Jin, and Bin Wang. "Loss of NSE-4 Perturbs Genome Stability and DNA Repair in Caenorhabditis elegans." International Journal of Molecular Sciences 23, no. 13 (June 29, 2022): 7202. http://dx.doi.org/10.3390/ijms23137202.

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The Structural Maintenance of Chromosomes (SMC) complex plays an important role in maintaining chromosome integrity, in which the SMC5/6 complex occupies a central position by facilitating mitotic and meiotic processes as well as DNA repair. NSE-4 Kleisin is critical for both the organization and function of the SMC5/6 complex, bridging NSE1 and NSE3 (MAGE related) with the head domains of the SMC5 and SMC6 proteins. Despite the conservation in protein sequence, no functional relevance of the NSE-4 homologous protein (NSE-4) in Caenorhabditis elegans has been reported. Here, we demonstrated the essential role of C. elegans NSE-4 in genome maintenance and DNA repair. Our results showed that NSE-4 is essential for the maintenance of chromosomal structure and repair of a range of chemically induced DNA damage. Furthermore, NSE-4 is involved in inter-sister repair during meiosis. NSE-4 localizes on the chromosome and is indispensable for the localization of NSE-1. Collectively, our data from this study provide further insight into the evolutionary conservation and diversification of NSE-4 function in the SMC-5/6 complex.

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15

Kozakova, Lucie, Lucie Vondrova, Karel Stejskal, Panagoula Charalabous, Peter Kolesar, Alan R. Lehmann, Stjepan Uldrijan, Christopher M. Sanderson, Zbynek Zdrahal, and Jan J. Palecek. "The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex." Cell Cycle 14, no. 6 (March 19, 2015): 920–30. http://dx.doi.org/10.1080/15384101.2014.1000112.

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16

Fonseca, Jeferson F., Maria Emilia F. Oliveira, Felipe Z. Brandão, Ribrio I. T. P. Batista, Alexandre R. Garcia, Pawel M. Bartlewski, and Joanna M. G. Souza-Fabjan. "Non-surgical embryo transfer in goats and sheep: the Brazilian experience." Reproduction, Fertility and Development 31, no. 1 (2019): 17. http://dx.doi.org/10.1071/rd18324.

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Brazil has presented tremendous progress in non-surgical embryo transfer (NSET) in sheep and goats. New instruments and techniques for non-surgical embryo recovery (NSER) and NSET in small ruminants were implemented. Recent improvements include refinement of the protocols for cervical relaxation combining oestradiol–oxytocin–cloprostenol treatment at specific times before NSER in sheep; recipient goats do not require any hormonal drugs to induce cervical dilation and direct embryo transfer by the cervical route yields excellent results. Transrectal ovarian ultrasonography (B-mode but especially colour Doppler) have proven to be accurate methods to localise and enumerate corpora lutea and luteinised unovulated follicles in recipient and donor does and ewes. An array of new criteria for selecting superior animals for NSER and NSET (e.g. cervical mapping) have been developed by Brazilian researchers. Extensive studies on both technologies were initially conducted in commercial breeds of goats and sheep but have been gradually extended to some native breeds of sheep (germplasm conservation) and dairy goat operations. It is speculated that, in future, NSER and NSET may become methods of choice for caprine and ovine embryo recovery and transfer in Brazil, and then globally. Due primarily to the efficiency of NSET in goats, a novel interspecies (e.g. bovine) IVP method may soon be developed on a large scale. The Brazilian experience is an invaluable source of information and know-how promoting the replacement of conventional surgical assisted reproductive technologies with non-surgical procedures and hence supporting the rapid development of the embryo transfer industry in small ruminants.

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17

Egbelakin, Temitope, Itohan E. Yakubu, and Justin Bowden. "Enhancing seismic regulatory compliance practices for non-structural elements in New Zealand." Bulletin of the New Zealand Society for Earthquake Engineering 51, no. 1 (March 31, 2018): 47–54. http://dx.doi.org/10.5459/bnzsee.51.1.47-54.

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Most non-structural elements (NSEs) including ceilings, piping, services equipment and cladding systems, etc., are typically prone to failure in the event of relatively low to medium earthquake shakings. The poor performance of NSEs demonstrated in recent earthquake events in New Zealand has revealed a gap in NSE design and construction practices, especially regarding compliance with the NSE performance standard (NZS 4219:2009). This study sought to examine the NZ 4219:2009 and compliance in New Zealand’s construction industry, towards improving the performance of NSEs during earthquakes.Using a face-to-face interview enquiry technique, findings from this study revealed that although majority of the participants consider the NZS 4219:2009 to be very important in improving the performance of NSEs during earthquakes, some shortcomings were also identified: (i) non-compliance with the NZ 4219:2009 by construction professionals; (ii) exclusion of guidelines for specific NSEs from the scope of the NZS 4219:2009; (iii) poor ease of use of the NZS 4219:2009 and other relevant excluded NSE guidelines; and (iv) lack of clarity in the NZS 4219:2009 regarding attribution of ultimate design responsibility for NSE seismic coordination. As a recommendation, the establishment of a robust, simple-to-use seismic specification document that will provide one-stop specifications for the design and installation of NSEs could be a possible solution to promoting strong compliance practices within the New Zealand construction industry, towards achieving improved performance of NSEs during earthquakes.

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18

Pathare, Neeti, Rachel Kimball, Elizabeth Donk, Kyle Kennedy, and Mellissa Perry. "Physical performance measures following ten weeks of taekwondo training in children: A pilot study." International Journal of Physical Education, Fitness and Sports 7, no. 3 (September 30, 2018): 1–11. http://dx.doi.org/10.26524/ijpefs1831.

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The primary purpose was to examine changes in balance, lower extremity (LE) power and flexibility following 10 weeks of taekwondo (TKD) training and to determine if this was different in children classified as healthy weight (HW) and overweight (OW)/obese. Participants included 17 children (HW: n = 11, OW/obese: n = 6). Data were collected on balance, LE power and flexibility at baseline and 10 weeks. Balance was assessed with eyes open in normal (NSEO), tandem (TSEO), single (SLEO) stances and with eyes closed for normal (NSEC) and tandem (TSEC) stances. Center of pressure displacements in mediolateral (Xavg) and anteroposterior (Yavg) directions; and average velocity (Vavg) were calculated. Analyses included two-way ANOVA and Mann Whitney U tests (P < 0.05). Balance data indicated significant interaction effects for Xavg in NSEO, Yavg in TSEO; time effects for Yavg in NSEO, NSEC and SLEO and Vavg in SLEO conditions. A significant group effect was shown for Vavg in the NSEO, NSEC and TSEO and for Yavg in TSEC conditions. Flexibility decreased significantly with TKD. Findings suggest that 10 weeks of TKD training may improve balance in children, and OW/obese group may have greater improvements in balance with eyes open compared to their peers.

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19

Pebernard, Stephanie, James Wohlschlegel, W. Hayes McDonald, John R. Yates, and Michael N. Boddy. "The Nse5-Nse6 Dimer Mediates DNA Repair Roles of the Smc5-Smc6 Complex." Molecular and Cellular Biology 26, no. 5 (March 1, 2006): 1617–30. http://dx.doi.org/10.1128/mcb.26.5.1617-1630.2006.

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ABSTRACT Stabilization and processing of stalled replication forks is critical for cell survival and genomic integrity. We characterize a novel DNA repair heterodimer of Nse5 and Nse6, which are nonessential nuclear proteins critical for chromosome segregation in fission yeast. The Nse5/6 dimer facilitates DNA repair as part of the Smc5-Smc6 holocomplex (Smc5/6), the basic architecture of which we define. Nse5-Nes6 (Nse5/6) mutants display a high level of spontaneous DNA damage and mitotic catastrophe in the absence of the master checkpoint regulator Rad3 (hATR). Nse5/6 mutants are required for the response to genotoxic agents that block the progression of replication forks, acting in a pathway that allows the tolerance of irreparable UV lesions. Interestingly, the UV sensitivity of Nse5/6 mutants is suppressed by concomitant deletion of the homologous recombination repair factor, Rhp51 (Rad51). Further, the viability of Nse5/6 mutants depends on Mus81 and Rqh1, factors that resolve or prevent the formation of Holliday junctions. Consistently, the UV sensitivity of cells lacking Nse5/6 can be partially suppressed by overexpressing the bacterial resolvase RusA. We propose a role for Nse5/6 mutants in suppressing recombination that results in Holliday junction formation or in Holliday junction resolution.

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20

Pebernard, Stephanie, James Wohlschlegel, W. Hayes McDonald, John R. Yates, and Michael N. Boddy. "The Nse5-Nse6 Dimer Mediates DNA Repair Roles of the Smc5-Smc6 Complex." Molecular and Cellular Biology 26, no. 8 (April 15, 2006): 3336. http://dx.doi.org/10.1128/mcb.26.8.3336.2006.

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21

Srivastava, Aishwarya, Sandhya Saisubramanian, Praveen Paruchuri, Akshat Kumar, and Shlomo Zilberstein. "Planning and Learning for Non-markovian Negative Side Effects Using Finite State Controllers." Proceedings of the AAAI Conference on Artificial Intelligence 37, no. 12 (June 26, 2023): 15144–51. http://dx.doi.org/10.1609/aaai.v37i12.26767.

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Autonomous systems are often deployed in the open world where it is hard to obtain complete specifications of objectives and constraints. Operating based on an incomplete model can produce negative side effects (NSEs), which affect the safety and reliability of the system. We focus on mitigating NSEs in environments modeled as Markov decision processes (MDPs). First, we learn a model of NSEs using observed data that contains state-action trajectories and severity of associated NSEs. Unlike previous works that associate NSEs with state-action pairs, our framework associates NSEs with entire trajectories, which is more general and captures non-Markovian dependence on states and actions. Second, we learn finite state controllers (FSCs) that predict NSE severity for a given trajectory and generalize well to unseen data. Finally, we develop a constrained MDP model that uses information from the underlying MDP and the learned FSC for planning while avoiding NSEs. Our empirical evaluation demonstrates the effectiveness of our approach in learning and mitigating Markovian and non-Markovian NSEs.

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22

Wehrkamp-Richter, S., R. W. Hyppa, J. Prudden, G. R. Smith, and M. N. Boddy. "Meiotic DNA joint molecule resolution depends on Nse5-Nse6 of the Smc5-Smc6 holocomplex." Nucleic Acids Research 40, no. 19 (August 1, 2012): 9633–46. http://dx.doi.org/10.1093/nar/gks713.

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23

Solé-Soler, Roger, and Jordi Torres-Rosell. "Smc5/6, an atypical SMC complex with two RING-type subunits." Biochemical Society Transactions 48, no. 5 (September 23, 2020): 2159–71. http://dx.doi.org/10.1042/bst20200389.

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The Smc5/6 complex plays essential roles in chromosome segregation and repair, by promoting disjunction of sister chromatids. The core of the complex is constituted by an heterodimer of Structural Maintenance of Chromosomes (SMC) proteins that use ATP hydrolysis to dynamically associate with and organize chromosomes. In addition, the Smc5/6 complex contains six non-SMC subunits. Remarkably, and differently to other SMC complexes, the Nse1 and Nse2 subunits contain RING-type domains typically found in E3 ligases, pointing to the capacity to regulate other proteins and complexes through ubiquitin-like modifiers. Nse2 codes for a C-terminal SP-RING domain with SUMO ligase activity, assisting Smc5/6 functions in chromosome segregation through sumoylation of several chromosome-associated proteins. Nse1 codes for a C-terminal NH-RING domain and, although it has been proposed to have ubiquitin ligase activity, no Smc5/6-dependent ubiquitylation target has been described to date. Here, we review the function of the two RING domains of the Smc5/6 complex in the broader context of SMC complexes as global chromosome organizers of the genome.

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24

Saisubramanian, Sandhya, Ece Kamar, and Shlomo Zilberstein. "Avoiding Negative Side Effects of Autonomous Systems in the Open World." Journal of Artificial Intelligence Research 74 (May 10, 2022): 143–77. http://dx.doi.org/10.1613/jair.1.13581.

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Autonomous systems that operate in the open world often use incomplete models of their environment. Model incompleteness is inevitable due to the practical limitations in precise model specification and data collection about open-world environments. Due to the limited fidelity of the model, agent actions may produce negative side effects (NSEs) when deployed. Negative side effects are undesirable, unmodeled effects of agent actions on the environment. NSEs are inherently challenging to identify at design time and may affect the reliability, usability and safety of the system. We present two complementary approaches to mitigate the NSE via: (1) learning from feedback, and (2) environment shaping. The solution approaches target settings with different assumptions and agent responsibilities. In learning from feedback, the agent learns a penalty function associated with a NSE. We investigate the efficiency of different feedback mechanisms, including human feedback and autonomous exploration. The problem is formulated as a multi-objective Markov decision process such that optimizing the agent’s assigned task is prioritized over mitigating NSE. A slack parameter denotes the maximum allowed deviation from the optimal expected reward for the agent’s task in order to mitigate NSE. In environment shaping, we examine how a human can assist an agent, beyond providing feedback, and utilize their broader scope of knowledge to mitigate the impacts of NSE. We formulate the problem as a human-agent collaboration with decoupled objectives. The agent optimizes its assigned task and may produce NSE during its operation. The human assists the agent by performing modest reconfigurations of the environment so as to mitigate the impacts of NSE, without affecting the agent’s ability to complete its assigned task. We present an algorithm for shaping and analyze its properties. Empirical evaluations demonstrate the trade-offs in the performance of different approaches in mitigating NSE in different settings.

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Braun, Alexander, Thomas Germann, Felix Wünnemann, Marc-André Weber, Marcus Schiltenwolf, Michael Akbar, Iris Burkholder, Hans-Ulrich Kauczor, and Christoph Rehnitz. "Impact of MRI, CT, and Clinical Characteristics on Microbial Pathogen Detection Using CT-Guided Biopsy for Suspected Spondylodiscitis." Journal of Clinical Medicine 9, no. 1 (December 21, 2019): 32. http://dx.doi.org/10.3390/jcm9010032.

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Spondylodiscitis accounts for 2–7% of osteomyelitis cases and is characterized by pain, systemic inflammation, and permanent neurological deficits. We aimed to identify imaging characteristics and clinical parameters to successfully predict microbiological pathogens by computed tomography (CT)-guided biopsy in suspected spondylodiscitis cases. Forty consecutive patients (mean age 65.1 years) with suspected spondylodiscitis underwent CT-guided biopsy. CT features (non-sclerotic endplate erosions (NSEs)), magnetic resonance criteria (paravertebral/epidural abscess (PA/EA) formation), and clinical data (C-reactive protein (CRP) > 50 mg/L) were assessed for their predictive potential. NSEs were detected in 6/11 (54.5%) and 1/29(3.4%) patients with positive and negative microbiology, respectively. PA and EA, respectively, were present in 7/11(63.6%) and 3/11 patients with positive microbiology and 7/29 (24.1%) and 2/29 patients with negative microbiology. CRP > 50 was observed in 7/11 (63.6%) and in 7/29 (24.1%) patients with positive and negative microbiology, respectively. Three double combinations possessed near-perfect specificity (PA + NSE, 100%; PA + CRP > 50, 96.6%; NSE + CRP > 50, 96.6%). The top three Youden indices included combinations with NSE. Since CT/magnetic resonance (MR) imaging and CRP are routinely used to evaluate spondylodiscitis, the presented diagnostic criteria and combinations can aid decision-making for biopsy.

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Kara, Cengiz, Ozgu Aydogdu, Ural Oguz, and Mehmet Giray Sönmez. "Effect of Varicocelectomy on the Frequency of Nocturnal Sperm Emissions." American Journal of Men's Health 10, no. 3 (September 7, 2015): 250–53. http://dx.doi.org/10.1177/1557988315598833.

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The aim of this study was to investigate the frequency of nocturnal sperm emissions (NSE) in varicocele patients after varicocele surgery. A total of 127 patients, 96 varicocele (Group 1) and 31 patients with inguinal hernia (Group 2) were included in this study. Mean age, laterality of surgical procedures, spermiogram results, marital status, and postoperative serum hormone levels were noted for all patients. Two groups were compared in terms of Beck depression score (BDS) and anxiety scores (AS). The frequency of NSE and libido changes in the patients during 10 days postoperatively was evaluated. The number of the patients who had NSE and increased libido were significantly higher in the varicocelectomy group when compared with the control group. No significant difference was noted between the groups in terms of BDS, AS, and serum hormone levels. No association was reported between BDS, AS, and serum hormone levels and the presence of NSE in Group 1. The incidence of NSE was higher in younger men. Increased libido was significantly associated with NSE in Group 1. Cord dissection during surgery may be a factor on increased frequency of NSEs in varicocele patients.

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McDonald, W. Hayes, Yelena Pavlova, John R. Yates, and Michael N. Boddy. "Novel Essential DNA Repair Proteins Nse1 and Nse2 Are Subunits of the Fission Yeast Smc5-Smc6 Complex." Journal of Biological Chemistry 278, no. 46 (September 8, 2003): 45460–67. http://dx.doi.org/10.1074/jbc.m308828200.

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Quintana Salinas, Margot Rosario. "Beneficios y barreras percibidos para consumir alimentos de origen animal entre embarazadas de diferente nivel socioeconómico - Lima." Anales de la Facultad de Medicina 77, no. 4 (December 16, 2016): 351. http://dx.doi.org/10.15381/anales.v77i4.12651.

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Introducción. La anemia en embarazadas es problema de salud pública en Perú. Una estrategia para prevenirla es la diversificación dietaria que incluya alimentos de origen animal (AOA), fuentes de hierro y otros nutrientes de alta biodisponibilidad. Los beneficios y barreras percibidos para consumir estos alimentos pueden ser diferentes según nivel socioeconómico. Objetivo. Comparar los beneficios y barreras percibidos sobre consumo de AOA entre embarazadas de diferente nivel socioeconómico. Diseño. Estudio cualitativo, diseño fenomenológico. Institución. Un establecimiento de Salud ubicado en Carabayllo (nivel socioeconómico bajo: NSEB) y otro en Magdalena del Mar (nivel socioeconómico medio: NSEM). Muestra. 20 embarazadas por nivel socioeconómico, elegidas intencionalmente según edad, paridad, peso corporal. Intervenciones. Entrevistas en profundidad y grupos focales, previo consentimiento informado. Principales medidas de resultados. Beneficios y barreras para consumir AOA durante la gestación: carnes y derivados, pescados, lácteos, huevos. Resultados. Se hallaron más beneficios similares que diferentes entre ambos grupos de embarazadas, alto valor nutritivo, buenos para bebe y madre, evitan la anemia, los huevos y el pollo son versátiles y prácticos en preparar, el pescado y el hígado son más nutritivos entre las carnes. También hubo barreras similares: poca accesibilidad por costo, desagrado, poca costumbre de consumo, escasa higiene e inocuidad y características organolépticas intensas (olor, sabor). Confusión del valor nutritivo en NSEB, poca habilidad en preparación de alimentos en NSEM. Conclusiones. Hubo más similitudes que diferencias en los beneficios y barreras percibidos sobre alimentos de origen animal entre embarazadas participantes de diferente nivel socioeconómico.

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Li, Gang, Wenxuan Zou, Liufang Jian, Jie Qian, and Jie Zhao. "AtNSE1 and AtNSE3 are required for embryo pattern formation and maintenance of cell viability during Arabidopsis embryogenesis." Journal of Experimental Botany 70, no. 21 (August 13, 2019): 6229–44. http://dx.doi.org/10.1093/jxb/erz373.

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Abstract Embryogenesis is an essential process during seed development in higher plants. It has previously been shown that mutation of the Arabidopsis non-SMC element genes AtNSE1 or AtNSE3 leads to early embryo abortion, and their proteins can interact with each other directly. However, the crucial regions of these proteins in this interaction and how the proteins are cytologically involved in Arabidopsis embryo development are unknown. In this study, we found that the C-terminal including the Ring-like motif of AtNSE1 can interact with the N-terminal of AtNSE3, and only the Ring-like motif is essential for binding with three α motifs of AtNSE2 (homologous to AtMMS21). Using genetic assays and by analysing molecular markers of cell fate decisions (STM, WOX5, and WOX8) in mutant nse1 and nse3 embryos, we found that AtNSE1 and AtNSE3 work non-redundantly in early embryo development, and that differentiation of the apical meristem and the hypophysis fails in the mutants, which have disrupted auxin transportation and responses. However, the upper cells of the suspensor in the mutants seem to have proper embryo cell identity. Cytological examination showed that cell death occurred from the early embryo stage, and that vacuolar programmed cell death and necrosis in the nse1 and nse3 mutant embryos led to ovule abortion. Thus, AtNSE1 and AtNSE3 are essential for maintaining cell viability and growth during early embryogenesis. Our results improve our understanding of the functions of SMC5/6 complex in early embryogenesis in Arabidopsis.

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Matias, Neyfsom Carlos Fernandes. "Relações entre Nível Socioeconômico, Atividades Extracurriculares e Alfabetização." Psico-USF 23, no. 3 (July 2018): 567–78. http://dx.doi.org/10.1590/1413-82712018230314.

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Resumo Este estudo investigou as implicações do nível socioeconômico (NSE) na alfabetização, na inserção de crianças em atividades oferecidas por organizações não governamentais (ONGs) e os impactos dessas ações no desempenho escolar. A amostra da pesquisa foi composta por 560 estudantes do segundo ano de escolarização de oito escolas municipais de Belo Horizonte (MG), sendo que 301 eram do sexo masculino e 259 do sexo feminino. Os dados utilizados foram os resultados da Provinha Brasil e os NSEs das escolas. Os resultados indicaram que a taxa de alunos alfabetizados não ultrapassou 62,00% do total da amostra, a interferência do NSE no rendimento acadêmico e na vinculação dos estudantes com as ONGs. Conclui-se que o NSE impacta no desempenho escolar no início da alfabetização, na busca das famílias por locais para deixar suas crianças em segurança, como as ONGs, e as ações dessas instituições influenciaram indiretamente o processo de alfabetização.

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NAZERIEH, Hossein, Zahra ORAGHI ARDEBILI, and Alireza IRANBAKHSH. "Potential benefits and toxicity of nanoselenium and nitric oxide in peppermint." Acta agriculturae Slovenica 111, no. 2 (October 29, 2018): 357. http://dx.doi.org/10.14720/aas.2018.111.2.11.

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Taking account of nano-compounds and biofortification, this research was conducted to evaluate peppermint (Mentha x piperita L.) responses to nano-selenium (nSe; 0, 2, and 20 mg l-1) and/or nitric oxide (NO; 0 and 8 mg l-1). Significant increases in leaf length, and area, and shoot fresh mass were enhanced by the low level of nSe and/or NO, contrasted with the high dose. The inhibitory effects of the high dose of nSe on the growth-related characteristics were significantly mitigated by NO. The adverse impact of nSe20 on chlorophyll concentration was alleviated by NO. The individual and combined treatments of nSe2 led to the significant inductions in the activities of nitrate reductase and peroxidase, whereas nSe20 inhibited. The proline contents in the nSe and/or NO-treated plants were higher than in the control. The nSe and/or NO provoked stimulation in activities of phenylalanine ammonia lyase enzyme. The foliar applications of nSe and/or NO triggered the accumulations of soluble phenols. Interestingly, the toxicity of nSe at the high dose led to the severe cell destruction in the cortex layer of the basal stem, which was partially alleviated by NO. The simultaneous applications of these supplements may consider as an alternative strategy for fortifying and improving plant protection, regarding sustainable agriculture.

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Odipo, Martin K., Tobias Olweny, and Oluoch Oluoch. "Firm Ownership Characteristics and Long-run Return on Equity Issued: A Case of the Nairobi Securities Exchange." Journal of Economics and Public Finance 7, no. 3 (May 27, 2021): p131. http://dx.doi.org/10.22158/jepf.v7n3p131.

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This investigation looked at the link between firm ownership characteristics and long-run return on firms that issued equity at the Nairobi Securities Exchange (NSE) in Kenya. The study covered 12 firms that issued shares in the NSE market from 2006-2008. Ownership characteristics included (state ownership, institutional Ownership, foreign Ownership, big five shareholders, market capitalization, age of the firm and Leverage of the firm) in relation to the average return. The study tested whether each of the firm ownership characteristics influenced long-run performance. Annual return for these companies was based on market return for five years after the firm’s equity shares were issued. The long-run performance was compared with three benchmarks, namely, NSE index, CAPM and Matching firms. Seven hypotheses were developed for the study. Simple-liner and multi-linear regression analyses based on panel data were carried out to relate the extended run return on shares issued. The result of the survey showed that issuing firms performed better than non-issuing firms. These issuing firms also performed better in comparison to CAPM. However, the issuing firms performed worse than NSEI. In conclusion, the long-run performance of equity issued at the NSE does not necessarily underperform relative to non-issuing establishments.

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Gray, Joshua P., Delaine Zayasbazan Burgos, Tao Yuan, Navindra Seeram, Rebecca Rebar, Rebecca Follmer та Emma A. Heart. "Thymoquinone, a bioactive component ofNigella sativa, normalizes insulin secretion from pancreatic β-cells under glucose overload via regulation of malonyl-CoA". American Journal of Physiology-Endocrinology and Metabolism 310, № 6 (15 березня 2016): E394—E404. http://dx.doi.org/10.1152/ajpendo.00250.2015.

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Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. TQ and NSE regulated NAD(P)H/NAD(P)+ratios via a quinone-dependent redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload. This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl-CoA, elevation of acetyl-CoA carboxylase (ACC), fatty acid synthase, and fatty acid-binding proteins following chronic glucose overload. Together, these data suggest that TQ modulates the β-cell redox circuitry and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under normal conditions as well as under hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of ACC and malonyl-CoA.

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Winkler, Ingo. "Non-standard employment and leadership research: On consequences for conceptualizing the leader–follower relationship." Leadership 7, no. 4 (November 2011): 499–511. http://dx.doi.org/10.1177/1742715011417496.

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The article argues that non-standard employees (NSEs) perceive the employee–employer relationship and hence the leader–follower relationship differently, when compared to workers in standard employment contracts. It highlights relevant differences between employees in flexible employment contracts and standard employees. It seeks to demonstrate that the emerging NSE-follower has consequences for leadership research. Perhaps the most important ramification is that the implicit assumptions in conceptualizing the ‘typical’ leader–follower relationship may no longer be suitable, facing today's workplace reality. In this sense, in order to take the present and continuous changes in the workforce seriously the concepts and theories used in leadership research need to be rethought.

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Wani, Saima, Neelam Maharshi, Deepash Kothiwal, Lakshmi Mahendrawada, Raju Kalaivani, and Shikha Laloraya. "Interaction of the Saccharomyces cerevisiae RING-domain protein Nse1 with Nse3 and the Smc5/6 complex is required for chromosome replication and stability." Current Genetics 64, no. 3 (November 8, 2017): 599–617. http://dx.doi.org/10.1007/s00294-017-0776-6.

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Barrette-Ng, Isabelle H., Kenneth K. S. Ng, Brian L. Mark, Danny van Aken, Maia M. Cherney, Craig Garen, Yuliya Kolodenko, Alexander E. Gorbalenya, Eric J. Snijder, and Michael N. G. James. "Structure of Arterivirus nsp4." Journal of Biological Chemistry 277, no. 42 (August 5, 2002): 39960–66. http://dx.doi.org/10.1074/jbc.m206978200.

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Morikawa, Hirofumi, Takashi Morishita, Shiho Kawane, Hiroshi Iwasaki, Antony M. Carr, and Hideo Shinagawa. "Rad62 Protein Functionally and Physically Associates with the Smc5/Smc6 Protein Complex and Is Required for Chromosome Integrity and Recombination Repair in Fission Yeast." Molecular and Cellular Biology 24, no. 21 (November 1, 2004): 9401–13. http://dx.doi.org/10.1128/mcb.24.21.9401-9413.2004.

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ABSTRACT Smc5 and Smc6 proteins form a heterodimeric SMC (structural maintenance of chromosome) protein complex like SMC1-SMC3 cohesin and SMC2-SMC4 condensin, and they associate with non-SMC proteins Nse1 and Nse2 stably and Rad60 transiently. This multiprotein complex plays an essential role in maintaining chromosome integrity and repairing DNA double strand breaks (DSBs). This study characterizes a Schizosaccharomyces pombe mutant rad62-1, which is hypersensitive to methyl methanesulfonate (MMS) and synthetically lethal with rad2 (a feature of recombination mutants). rad62-1 is hypersensitive to UV and gamma rays, epistatic with rhp51, and defective in repair of DSBs. rad62 is essential for viability and genetically interacts with rad60, smc6, and brc1. Rad62 protein physically associates with the Smc5-6 complex. rad62-1 is synthetically lethal with mutations in the genes promoting recovery from stalled replication, such as rqh1, srs2, and mus81, and those involved in nucleotide excision repair like rad13 and rad16. These results suggest that Rad62, like Rad60, in conjunction with the Smc5-6 complex, plays an essential role in maintaining chromosome integrity and recovery from stalled replication by recombination.

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Fenske, Dieter, Andreas Frankenau, and Kurt Dehnicke. "Komplexe mit dem (NSeMe)2--Liganden. Die Kristallstruktur von [PPh3Me][Cl5W(NSeMe)] / Complexes with the Ligand (NSeMe)2-. The Crystal Structure of [PPh3Me][Cl5W(NSeMe)]." Zeitschrift für Naturforschung B 45, no. 4 (April 1, 1990): 427–32. http://dx.doi.org/10.1515/znb-1990-0404.

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[CH3CN—WCl4(NSeMe)] and [PPh3Me][Cl5W(NSeMe)] have been prepared by the reaction of Me3SiSeMe with [CH3CN—WCl4(NCl)] and [PPh3Me][WCl5(NCl)], respectively, as brown, moisture sensitive crystals which were characterized by IR spectroscopy. The crystal structure of [PPh3Me][Cl5W(NSeMe)] was determined: Space group PĪ, Z = 4, 7599 observed unique reflexions, R = 0.046. Lattice dimensions at —70°C: α = 1104.6(6), b = 1489.2(9), c = 1650.6(8) pm, α = 108.37(4)°, β = 90.71(4)°, γ = 93.83(4)°. The compound forms ions [PPh3Me]+ and [Cl5W(NSeMe)]-, in which the tungsten atoms is octahedrally coordinated by five chlorine atoms and by the nitrogen atom of the (NSeMe)2- ligand. The bond lengths WN 171.6(8), NSe 180.6(9) pm and bond angles WNSe 173.6(7)°, NSeC 98.3(5)° (in average of the two independent anions) are in agreement with the proposed formula W ≡ N—Se—Me ↔W = N = Se—Me.

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Bøhler, Linn, and Ida Marie Pedersen. "Referat fra NSEs høstseminar: Tarmhelse." Norsk tidsskrift for ernæring 17, no. 4 (December 2019): 1–5. http://dx.doi.org/10.18261/ntfe.17.4.17.

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Touhami, Slimane. "Pe(a)nser les exils." Sociographe N° 76, no. 5 (November 10, 2021): 9–11. http://dx.doi.org/10.3917/graph1.076.0009.

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Kohls, Niko, Harald Walach, and George Lewith. "The Impact of Positive and Negative Spiritual Experiences on Distress and the Moderating Role of Mindfulness." Archive for the Psychology of Religion 31, no. 3 (September 2009): 357–74. http://dx.doi.org/10.1163/008467209x12524724282032.

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Both spiritual experiences and mindfulness as a psychological variable have been identified as components of wellbeing and health. As there is uncertainty about their relationship, we have investigated the impact of spiritual experiences and mindfulness as well as their interaction on distress in chronically ill patients. The unidimensional Daily Spiritual Experiences Scale (DSES), the multidimensional Exceptional Experiences Questionnaire (EEQ), the Freiburg Mindfulness Inventory (FMI), and the Brief Symptom Inventory (BSI) were administered to 109 chronically ill patients. Fifty-eight patients (53%) reported regular and frequent spiritual or contemplative practice from different traditions over an average of 14.7 years (SD = 13.7). Patients with regular spiritual practice reported more positive spiritual experiences, were more mindful and less distressed (p < .001). A stepwise linear regression analysis revealed that the EEQ subscale “negative spiritual experiences” (NSE) was the most important single predictor for psychological distress (R2=.38; β=.63). In contrast, both the EEQ subscale “positive spiritual experiences” as well as the DSES that also captures positives daily encounters with a transcendental realm or entity did not account for a significant amount of variance in distress. Further analysis of the regression model (R2=.57), confirmed that NSE was still the largest predictor for distress (β=.61) and that mindfulness (β=–.38) and the interaction between mindfulness and NSE (β=–.23) were the most important buffers protecting individuals from distress. Thus, mindfulness seems not only to be a clinically important protective factor for buffering generic distress, but particularly for distress derived from NSEs. This suggests that in addition to directly facilitating well-being and health by means of positive spiritual experiences, at least some form of regular spiritual or meditative techniques seem to endow an individual with a certain degree of resilience against negative spiritual experiences that is likely a consequence of increased mindfulness. If these findings are vindicated by further studies, spiritual experiences should not be conceived and measured as univariate but rather multivariate constructs.

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Chen, Ziyan, Deborah Falla, Edith Elgueta Cancino, and Janet A Deane. "Can baseline features predict a reduction in pain and disability following neck-specific exercise in people with chronic non-specific neck pain?: A systematic review and meta-analysis protocol." BMJ Open 13, no. 7 (July 2023): e074494. http://dx.doi.org/10.1136/bmjopen-2023-074494.

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IntroductionNeck-specific exercises (NSEs) are commonly used for the treatment of chronic non-specific neck pain (CNSNP). However, it remains unclear whether baseline features can predict the response to neck-specific exercise (NSE) in people with CNSNP. This systematic review aims to assess whether baseline features such as age, gender, muscle activity, fatigability, endurance and fear of movement can predict pain and disability reduction following a NSE intervention.Methods and analysisThis systematic review and meta-analysis will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols guidelines checklist. The Web of Science, PubMed, Scopus, MEDLINE, Embase and CINAHL databases; key journals; and grey literature will be searched up until June 2023, including medical subject heading terms and keywords combinations. Included studies will investigate an association between the baseline features and pain and disability outcomes following NSE in people with CNSNP. Two independent reviewers will oversee the searching, screening, data extraction and assessment of risk of bias. The risk of bias will be assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) and Risk-Of-Bias tool for randomised trials 2 (ROB 2). The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Using standardised forms, details regarding study characteristics, baseline features (predictive factors), intervention, primary outcome and effect size (OR and 95% CI of each predictive factor and p value) will be extracted from included studies. Meta-analyses will be considered, if the studies are sufficiently homogeneous and if three or more studies investigate the same or comparable factors that predict the same response (pain intensity or disability). In the event that less than three studies investigated the same factors, a narrative synthesis will be conducted.Ethics and disseminationEthical approval will not be required as this review will be based on published studies. The results of this study will be submitted to a peer-reviewed journal and presented at conferences.PROSPERO registration numberCRD42023408332.

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Camera, Corrado, Adriana Bruggeman, George Zittis, Ioannis Sofokleous, and Joël Arnault. "Simulation of extreme rainfall and streamflow events in small Mediterranean watersheds with a one-way-coupled atmospheric–hydrologic modelling system." Natural Hazards and Earth System Sciences 20, no. 10 (October 23, 2020): 2791–810. http://dx.doi.org/10.5194/nhess-20-2791-2020.

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Abstract. Coupled atmospheric–hydrologic systems are increasingly used as instruments for flood forecasting and water management purposes, making the performance of the hydrologic routines a key indicator of the model functionality. This study's objectives were (i) to calibrate the one-way-coupled WRF-Hydro model for simulating extreme events in Cyprus with observed precipitation and (ii) to evaluate the model performance when forced with WRF-downscaled (1×1 km2) re-analysis precipitation data (ERA-Interim). This set-up resembles a realistic modelling chain for forecasting applications and climate projections. Streamflow was modelled during extreme rainfall events that occurred in January 1989 (calibration) and November 1994 (validation) over 22 mountain watersheds. In six watersheds, Nash–Sutcliffe efficiencies (NSEs) larger than 0.5 were obtained for both events. The WRF-modelled rainfall showed an average NSE of 0.83 for January 1989 and 0.49 for November 1994. Nevertheless, hydrologic simulations of the two events with the WRF-modelled rainfall and the calibrated WRF-Hydro returned negative streamflow NSE for 13 watersheds in January 1989 and for 18 watersheds in November 1994. These results indicate that small differences in amounts or shifts in time or space of modelled rainfall, in comparison with observed precipitation, can strongly modify the hydrologic response of small watersheds to extreme events. Thus, the calibration of WRF-Hydro for small watersheds depends on the availability of observed rainfall with high temporal and spatial resolution. However, the use of modelled precipitation input data will remain important for studying the effect of future extremes on flooding and water resources.

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Storey, Stephen M., Thomas F. Gibbons, Cecelia V. Williams, Rebecca D. Parr, Friedhelm Schroeder, and Judith M. Ball. "Full-Length, Glycosylated NSP4 Is Localized to Plasma Membrane Caveolae by a Novel Raft Isolation Technique." Journal of Virology 81, no. 11 (March 21, 2007): 5472–83. http://dx.doi.org/10.1128/jvi.01862-06.

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ABSTRACT Rotavirus NSP4, initially characterized as an endoplasmic reticulum intracellular receptor, is a multifunctional viral enterotoxin that induces diarrhea in murine pups. There have been recent reports of the secretion of a cleaved NSP4 fragment (residues 112 to 175) and of the association of NSP4 with LC3-positive autophagosomes, raft membranes, and microtubules. To determine if NSP4 traffics to a specific subset of rafts at the plasma membrane, we isolated caveolae from plasma membrane-enriched material that yielded caveola membranes free of endoplasmic reticulum and nonraft plasma membrane markers. Analyses of the newly isolated caveolae from rotavirus-infected MDCK cells revealed full-length, high-mannose glycosylated NSP4. The lack of Golgi network-specific processing of the caveolar NSP4 glycans supports studies showing that NSP4 bypasses the Golgi apparatus. Confocal imaging showed the colocalization of NSP4 with caveolin-1 early and late in infection, elucidating the temporal and spatial NSP4-caveolin-1 association during infection. These data were extended with fluorescent resonance energy transfer analyses that confirmed the NSP4 and caveolin-1 interaction in that the specific fluorescently tagged antibodies were within 10 nm of each other during infection. Cells transfected with NSP4 showed patterns of staining and colocalization with caveolin-1 similar to those of infected cells. This study presents an endoplasmic reticulum contaminant-free caveola isolation protocol; describes the presence of full-length, endoglycosidase H-sensitive NSP4 in plasma membrane caveolae; provides confirmation of the NSP4-caveolin interaction in the presence and absence of other viral proteins; and provides a final plasma membrane destination for Golgi network-bypassing NSP4 transport.

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Berkova, Z., S. E. Crawford, G. Trugnan, T. Yoshimori, A. P. Morris, and M. K. Estes. "Rotavirus NSP4 Induces a Novel Vesicular Compartment Regulated by Calcium and Associated with Viroplasms." Journal of Virology 80, no. 12 (June 15, 2006): 6061–71. http://dx.doi.org/10.1128/jvi.02167-05.

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ABSTRACT Rotavirus is a major cause of infantile viral gastroenteritis. Rotavirus nonstructural protein 4 (NSP4) has pleiotropic properties and functions in viral morphogenesis as well as pathogenesis. Recent reports show that the inhibition of NSP4 expression by small interfering RNAs leads to alteration of the production and distribution of other viral proteins and mRNA synthesis, suggesting that NSP4 also affects virus replication by unknown mechanisms. This report describes studies aimed at correlating the localization of intracellular NSP4 in cells with its functions. To be able to follow the localization of NSP4, we fused the C terminus of full-length NSP4 with the enhanced green fluorescent protein (EGFP) and expressed this fusion protein inducibly in a HEK 293-based cell line to avoid possible cytotoxicity. NSP4-EGFP was initially localized in the endoplasmic reticulum (ER) as documented by Endo H-sensitive glycosylation and colocalization with ER marker proteins. Only a small fraction of NSP4-EGFP colocalized with the ER-Golgi intermediate compartment (ERGIC) marker ERGIC-53. NSP4-EGFP did not enter the Golgi apparatus, in agreement with the Endo H sensitivity and a previous report that secretion of an NSP4 cleavage product generated in rotavirus-infected cells is not inhibited by brefeldin A. A significant population of expressed NSP4-EGFP was distributed in novel vesicular structures throughout the cytoplasm, not colocalizing with ER, ERGIC, Golgi, endosomal, or lysosomal markers, thus diverging from known biosynthetic pathways. The appearance of vesicular NSP4-EGFP was dependent on intracellular calcium levels, and vesicular NSP4-EGFP colocalized with the autophagosomal marker LC3. In rotavirus-infected cells, NSP4 colocalized with LC3 in cap-like structures associated with viroplasms, the site of nascent viral RNA replication, suggesting a possible new mechanism for the involvement of NSP4 in virus replication.

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Zhang, Mingdong, Carl Q. Y. Zeng, Andrew P. Morris, and Mary K. Estes. "A Functional NSP4 Enterotoxin Peptide Secreted from Rotavirus-Infected Cells." Journal of Virology 74, no. 24 (December 15, 2000): 11663–70. http://dx.doi.org/10.1128/jvi.74.24.11663-11670.2000.

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ABSTRACT Previous studies have shown that the nonstructural glycoprotein NSP4 plays a role in rotavirus pathogenesis by functioning as an enterotoxin. One prediction of the mechanism of action of this enterotoxin was that it is secreted from virus-infected cells. In this study, the media of cultured (i) insect cells infected with a recombinant baculovirus expressing NSP4, (ii) monkey kidney (MA104) cells infected with the simian (SA11) or porcine attenuated (OSU-a) rotavirus, and (iii) human intestinal (HT29) cells infected with SA11 were examined to determine if NSP4 was detectable. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis–Western blotting, immunoprecipitation and N-terminal amino acid sequencing identified, in the early media from virus-infected cells, a secreted, cleavage product of NSP4 with an apparent molecular weight of 7,000 that represented amino acids 112 to 175 (NSP4 aa112–175). The secretion of NSP4 aa112–175 was not affected by treatment of cells with brefeldin A but was abolished by treatment with nocodazole and cytochalasin D, indicating that secretion of this protein occurs via a nonclassical, Golgi apparatus-independent mechanism that utilizes the microtubule and actin microfilament network. A partial gene fragment coding for NSP4 aa112–175 was cloned and expressed using the baculovirus-insect cell system. Purified NSP4 aa112–175 increased intracellular calcium mobilization in intestinal cells when added exogenously, and in insect cells when expressed endogenously, similarly to full-length NSP4. NSP4 aa112–175 caused diarrhea in neonatal mice, as did full-length NSP4. These results indicate that NSP4 aa112–175 is a functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells.

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Bhowmick, Rahul, Umesh Chandra Halder, Shiladitya Chattopadhyay, Shampa Chanda, Satabdi Nandi, Parikshit Bagchi, Mukti Kant Nayak, Oishee Chakrabarti, Nobumichi Kobayashi, and Mamta Chawla-Sarkar. "Rotaviral Enterotoxin Nonstructural Protein 4 Targets Mitochondria for Activation of Apoptosis during Infection." Journal of Biological Chemistry 287, no. 42 (August 10, 2012): 35004–20. http://dx.doi.org/10.1074/jbc.m112.369595.

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Viruses have evolved to encode multifunctional proteins to control the intricate cellular signaling pathways by using very few viral proteins. Rotavirus is known to express six nonstructural and six structural proteins. Among them, NSP4 is the enterotoxin, known to disrupt cellular Ca2+ homeostasis by translocating to endoplasmic reticulum. In this study, we have observed translocation of NSP4 to mitochondria resulting in dissipation of mitochondrial membrane potential during virus infection and NSP4 overexpression. Furthermore, transfection of the N- and C-terminal truncated NSP4 mutants followed by analyzing NSP4 localization by immunofluorescence microscopy identified the 61–83-amino acid region as the shortest mitochondrial targeting signal. NSP4 exerts its proapoptotic effect by interacting with mitochondrial proteins adenine nucleotide translocator and voltage-dependent anion channel, resulting in dissipation of mitochondrial potential, release of cytochrome c from mitochondria, and caspase activation. During early infection, apoptosis activation by NSP4 was inhibited by the activation of cellular survival pathways (PI3K/AKT), because PI3K inhibitor results in early induction of apoptosis. However, in the presence of both PI3K inhibitor and NSP4 siRNA, apoptosis was delayed suggesting that the early apoptotic signal is initiated by NSP4 expression. This proapoptotic function of NSP4 is balanced by another virus-encoded protein, NSP1, which is implicated in PI3K/AKT activation because overexpression of both NSP4 and NSP1 in cells resulted in reduced apoptosis compared with only NSP4-expressing cells. Overall, this study reports on the mechanism by which enterotoxin NSP4 exerts cytotoxicity and the mechanism by which virus counteracts it at the early stage for efficient infection.

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Boutten, Anne. "Énolase neurospécifique (NSE)." EMC - Biologie Médicale 1, no. 1 (January 2006): 1–3. http://dx.doi.org/10.1016/s2211-9698(06)76061-7.

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Odrzywolek, Andrzej. "NSE abundance data." Atomic Data and Nuclear Data Tables 98, no. 4 (July 2012): 852–61. http://dx.doi.org/10.1016/j.adt.2012.06.002.

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Xu, Menghua, Yongfeng Fu, Jiae Sun, Junqi Zhang, Meng Feng, Xunjia Cheng, and Jin Xu. "Analysis of Rotavirus NSP4 Genotypes and Age-Dependent Antibody Response against NSP4 in Shanghai, China." Japanese Journal of Infectious Diseases 63, no. 4 (July 30, 2010): 280–82. http://dx.doi.org/10.7883/yoken.63.280.

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