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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.02.035 Byline: Stephan Gruber (1), Jeff Errington (1) Keywords: CELLBIO; CELLCYCLE; MICROBIO Abstract: Proper segregation of DNA replication products is essential in all cells. In Bacillus subtilis, two protein complexes have been implicated in this process: the ParAB homologs, Soj and Spo0J, and the bacterial Smc/ScpAB complex, also called condensin. Here we demonstrate that Smc is highly enriched in the region around the origin of replication, specifically near parS sites to which Spo0J binds and at highly transcribed genes. Furthermore, we find that efficient recruitment of Smc to a large region around the origin of replication depends on the presence of Spo0J. We show that Spo0J performs two independent functions: regulation of initiation of DNA replication via Soj and promotion of chromosome segregation by Smc recruitment. Our results demonstrate a direct functional interaction between two widely conserved systems involved in chromosome replication and segregation. Author Affiliation: (1) Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK Article History: Received 1 October 2008; Revised 23 December 2008; Accepted 19 February 2009 Article Note: (miscellaneous) Published: May 14, 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.08.048 Byline: Stephan Gruber (1), Prakash Arumugam (1)(2), Yuki Katou (3), Daria Kuglitsch (1), Wolfgang Helmhart (1)(2), Katsuhiko Shirahige (3), Kim Nasmyth (1)(2) Abstract: Cohesin is a multisubunit complex that mediates sister-chromatid cohesion. Its Smc1 and Smc3 subunits possess ABC-like ATPases at one end of 50 nm long coiled coils. At the other ends are pseudosymmetrical hinge domains that interact to create V-shaped Smc1/Smc3 heterodimers. N- and C-terminal domains within cohesin's kleisin subunit Scc1 bind to Smc3 and Smc1 ATPase heads respectively, thereby creating a huge tripartite ring. It has been suggested that cohesin associates with chromosomes by trapping DNA within its ring. Opening of the ring due to cleavage of Scc1 by separase destroys sister-chromatid cohesion and triggers anaphase. We show that cohesin's hinges are not merely dimerization domains. They are essential for cohesin's association with chromosomes, which is blocked by artificially holding hinge domains together but not by preventing Scc1's dissociation from SMC ATPase heads. Our results suggest that entry of DNA into cohesin's ring requires transient dissociation of Smc1 and Smc3 hinge domains. Author Affiliation: (1) Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria (2) University of Oxford, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK (3) Gene Research Center, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, 226-8501 Yokohama, Japan Article History: Received 10 January 2006; Revised 30 June 2006; Accepted 21 August 2006 Article Note: (miscellaneous) Published: November 2, 2006

Analysis and prediction of permafrost change are hampered by lack of observational data. We implement a permafrost data management system to support multi-variable permafrost observation networks. It addresses five key challenges we identified for permafrost data management and publication: (1) existing data management strategies do not scale well, (2) data users have different skills and needs, (3) permafrost data are varied, (4) resources for permafrost data management are limited, and (5) existing permafrost data sources are difficult to integrate. This prototype system supports a workflow from observation to the distribution of interoperable data. It comprises a database with auxiliary software, a set of practices, and an ERDDAP server. We find the system simplifies data publication, hurdles in adapting CF conventions and ERDDAP for permafrost data remain, and technology cannot replace good practice. Our learning can inform organizations who collect, manage, or distribute permafrost data or those who manage large observation networks. [Display omitted] • Five broad challenges limit permafrost data management and publication. • Framed as requirements, the challenges share similarities with the FAIR principles. • We prototype a permafrost data system to support field-to-publication workflows. • We adopt and adapt standards and software for observational permafrost data. • Our data system supports the FAIR-ification of permafrost data. [ABSTRACT FROM AUTHOR]

Research points out that cohesin holds sister DNAs within a single ring and that all SMC protein complexes, like cohesin, allow passage of DNA inside two arms held together by Scc1-like bridges that open and close. This mechanism regulate the DNA packing within cells.

Three hypotheses exist to explain how meteorological variables drive the amount and concentration of solute-enriched water from rock glaciers: (1) Warm periods cause increased subsurface ice melt, which releases solutes; (2) rain periods and the melt of long-lasting snow enhance dilution of rock-glacier outflows; and (3) percolation of rain through rock glaciers facilitates the export of solutes, causing an opposite effect as that described in hypothesis (2). This lack of detailed understanding likely exists because suitable studies of meteorological variables, hydrologic processes and chemical characteristics of water bodies downstream from rock glaciers are unavailable. In this study, a rock-glacier pond in the North-Western Italian Alps was studied on a weekly basis for the ice-free seasons 2014 and 2015 by observing the meteorological variables (air temperature, snowmelt, rainfall) assumed to drive the export of solute-enriched waters from the rock glacier and the hydrochemical response of the pond (water temperature as a proxy of rock-glacier discharge, stable water isotopes, major ions and selected trace elements). An intra-seasonal pattern of increasing solute export associated with higher rock-glacier discharge was found. Specifically, rainfall, after the winter snowpack depletion and prolonged periods of atmospheric temperature above 0 °C, was found to be the primary driver of solute export from the rock glacier during the ice-free season. This occurs likely through the flushing of isotopically- and geochemically-enriched icemelt, causing concomitant increases in the rock-glacier discharge and the solute export (SO 4 2− , Mg 2+ , Ca 2+ , Ni, Mn, Co). Moreover, flushing of microbially-active sediments can cause increases in NO 3 − export. [ABSTRACT FROM AUTHOR]

Bacteria transcribe, duplicate and segregate their genomes all at once. Conflicts between DNA replication and active transcription are a major source of DNA damage and jeopardize genome integrity and cell survival. Co-orientation of replication forks and transcription units is thought to reduce the impact of such conflicts. Like transcription and replication, chromosome segregation relies on the translocation of multi-subunit protein complexes along DNA. Here, I highlight recent advances in our understanding of two major classes of structural maintenance of chromosomes (SMC) complexes in bacteria: Smc-ScpAB, whose DNA translocation is co-oriented with DNA replication by specific start sites, and MukBEF, which apparently lacks such co-ordination. Potential advantages of centralized and decentralized approaches to chromosome organization are discussed. [ABSTRACT FROM AUTHOR]

SMC proteins organize chromosomes to coordinate essential nuclear processes such as gene expression and DNA recombination as well as to segregate chromosomes during cell division. SMC mediated DNA bridging keeps sister chromatids aligned for much of the cell cycle, while the active extrusion of DNA loops by SMC presumably compacts chromosomes. Chromosome superstructure is thus given by the number of DNA linkages and the size of chromosomal DNA loops, which in turn depend on the dynamics of SMC loading and unloading. The latter is regulated by the intrinsic SMC ATPase activity, multiple external factors and post-translational modification. Here, I highlight recent advances in our understanding of DNA capture and release by SMC—with a focus on cohesin. [ABSTRACT FROM AUTHOR]

Summary Smc/ScpAB promotes chromosome segregation in prokaryotes, presumably by compacting and resolving nascent sister chromosomes. The underlying mechanisms, however, are poorly understood. Here, we investigate the role of the Smc ATPase activity in the recruitment of Smc/ScpAB to the Bacillus subtilis chromosome. We demonstrate that targeting of Smc/ScpAB to ParB/ parS loading sites is strictly dependent on engagement of Smc head domains and relies on an open organization of the Smc coiled coils. We find that dimerization of the Smc hinge domain stabilizes closed Smc rods and hinders head engagement as well as chromosomal targeting. Conversely, the ScpAB sub-complex promotes head engagement and Smc rod opening and thereby facilitates recruitment of Smc to parS sites. Upon ATP hydrolysis, Smc/ScpAB is released from loading sites and relocates within the chromosome—presumably through translocation along DNA double helices. Our findings define an intermediate state in the process of chromosome organization by Smc. [ABSTRACT FROM AUTHOR]

SMC/kleisin complexes form elongated annular structures, which are critical for chromosome segregation, genome maintenance, and the regulation of gene expression. We describe marked structural similarities between bacterial and eukaryotic SMC/kleisin partner proteins (designated here as “kite” proteins for k leisin i nteracting t andem winged-helix (WH) e lements of SMC complexes). Kite proteins are integral parts of all prokaryotic SMC complexes and Smc5/6 but not cohesin and condensin. They are made up of tandem WH domains, form homo- or heterodimers via their amino-terminal WH domain, and they associate with the central part of a kleisin subunit. In placental mammals, the kite subunit NSE3 gave rise to several (>60) kite-related proteins, named MAGE, many of which encode tumor- and testis-specific antigens. Based on architectural rather than sequence similarity, we propose an adapted model for the evolution of the SMC protein complexes and discuss potential functional similarities between bacterial Smc/ScpAB and eukaryotic Smc5/6. [ABSTRACT FROM AUTHOR]

Chromosomes readily unlink and segregate to daughter cells during cell division, highlighting a remarkable ability of cells to organize long DNA molecules. SMC complexes promote DNA organization by loop extrusion. In most bacteria, chromosome folding initiates at dedicated start sites marked by the ParB/ parS partition complexes. Whether SMC complexes recognize a specific DNA structure in the partition complex or a protein component is unclear. By replacing genes in Bacillus subtilis with orthologous sequences from Streptococcus pneumoniae , we show that the three subunits of the bacterial Smc complex together with the ParB protein form a functional module that can organize and segregate foreign chromosomes. Using chimeric proteins and chemical cross-linking, we find that ParB directly binds the Smc subunit. We map an interface to the Smc joint and the ParB CTP-binding domain. Structure prediction indicates how the ParB clamp presents DNA to the Smc complex, presumably to initiate DNA loop extrusion. [Display omitted] • The bacterial DNA-binding protein ParB interacts with the condensin-like Smc-ScpAB • Genetic mapping and structure predictions reveal an Smc joint-ParB binding interface • Mutating the binding interface hampers Smc recruitment but not other ParB functions • ParB and Smc-ScpAB form a transplantable unit for chromosome segregation in bacteria By transplanting Streptococcus genes into Bacillus subtilis , Bock et al. demonstrate that a four-gene module comprising genes encoding ParB and the condensin-like subunits Smc, ScpA, and ScpB can promote chromosome segregation in foreign bacteria. They elucidate a ParB-Smc protein-protein interface and show it is required for Smc recruitment by ParB. [ABSTRACT FROM AUTHOR]

All living cells have to master the extraordinarily extended and tangly nature of genomic DNA molecules — in particular during cell division when sister chromosomes are resolved from one another and confined to opposite halves of a cell. Bacteria have evolved diverse sets of proteins, which collectively ensure the formation of compact and yet highly dynamic nucleoids. Some of these players act locally by changing the path of DNA through the bending of its double helical backbone. Other proteins have wider or even global impact on chromosome organization, for example by interconnecting two distant segments of chromosomal DNA or by actively relocating DNA within a cell. Here, I highlight different modes of chromosome organization in bacteria and on this basis consider models for the function of SMC protein complexes, whose mechanism of action is only poorly understood so far. [ABSTRACT FROM AUTHOR]

Ice-wedges are periglacial landforms that develop as a result of thermal contraction-cracking in continuous permafrost regions, which appear as polygonal networks on the ground surface. Given their complex thermo-mechanical loading history, very few related numerical models have so far been developed. In this study, 2-D eXtended finite element simulations are employed to represent the formation process of ice-wedges and to investigate the effect of select environmental controls on crack initiation and growth. Seventeen combinations of soil type and temperature–time series are used in four case studies addressing model testing, the permafrost stress regime, the freezing volumetric expansion of porewater, and a new remeshing process introduced to simulate ice-wedge growth over multiple years. The model testing shows good agreement with field observations from the Arctic and demonstrates the ability of the modelling procedure to reproduce the salient features of thermal contraction-cracking. The permafrost stress regime is found to be strongly affected by soil type and climate, with coarse-grained soils and cold climates leading to higher tensile stresses than fine-grained soils and warm climates. Higher tensile stress are also predicted for saturated soils due to the freezing volumetric expansion of porewater. [ABSTRACT FROM AUTHOR]

Multi-subunit SMC ATPases control chromosome superstructure apparently by catalyzing a DNA-loop-extrusion reaction. SMC proteins harbor an ABC-type ATPase "head" and a "hinge" dimerization domain connected by a coiled coil "arm." Two arms in a SMC dimer can co-align, thereby forming a rod-shaped particle. Upon ATP binding, SMC heads engage, and arms are thought to separate. Here, we study the shape of Bacillus subtilis Smc-ScpAB by electron-spin resonance spectroscopy. Arm separation is readily detected proximal to the heads in the absence of ligands, and separation near the hinge largely depends on ATP and DNA. Artificial blockage of arm opening eliminates DNA stimulation of ATP hydrolysis but does not prevent basal ATPase activity. We report an arm contact as being important for controlling the transformations. Point mutations at this arm interface eliminated Smc function. We propose that partially open, intermediary conformations provide directionality to SMC DNA translocation by (un)binding suitable DNA substrates. [Display omitted] • Smc arms partially open in absence of ATP and DNA • ATP and DNA binding are essential for full opening of the arms • Single-residue substitutions in the arm are lethal, likely by altering Smc dynamics • Intermediary states may provide directionality to the Smc DNA translocation Using electron-spin resonance spectroscopy and cysteine crosslinking, Vazquez Nunez et al. reveal intermediary conformations of the bacterial Smc complex. Smc arms partially open in the absence of ligands, and Smc heads adopt an ATP-pre-engaged state. Gradual opening of the Smc arms may direct DNA substrate binding. [ABSTRACT FROM AUTHOR]

Chromosome segregation during mitosis and meiosis depends on the linkage of sister DNA molecules after replication. These links, known as sister-chromatid cohesion, are provided by a multi-subunit complex called cohesin. Recent papers suggest that chromatin-remodeling complexes also have a role in the generation of sister-chromatid cohesion. It remains unclear whether they do so by facilitating the recruitment of cohesin to specific chromosomal sequences or by modifying an event at replication forks giving rise to cohesion between sister DNAs. [Copyright &y& Elsevier]

• Evidence of significant permafrost areas in the cold-arid Ladakh Himalaya. • Comparable surface and thermal offsets with the Qinghai-Tibet Plateau region. • Elevation above 4900 m a.s.l. have higher chances of permafrost occurrence. • Active layer thickness range from 4.2 to 0.1 m and MAAT, −4.1 to −8.9 °C. Cold-arid regions of the trans-Himalaya in the Indian Himalayan Region (IHR) is suspected to have a significant area of permafrost. However, information on the ground thermal regime of these permafrost areas is so far not available. This study bridge this knowledge gap by analysing the sub-surface thermal regime of selected sites in the Ganglass catchment, Ladakh range. Near surface ground temperature data recorded during September 2016 to August 2017 using 24-miniature temperature data loggers distributed across 12 plots and covering an elevation range of 4700–5612 m a.s.l. are used in this study. Permafrost characteristics including plausible ranges of thermal offset, active-layer thickness and mean annual ground temperature at 10 m depth were estimated by driving a one-dimensional heat conduction model. Two statistical models were used to map first order estimates of permafrost area in this 15.4 km2 catchment. Study suggest permafrost occurrence at all sites above 4900 m a.s.l. with active-layer thickness ranging from 0.1 to 4.2 m and the mean annual ground surface temperature ranging from between −10.0 and −0.85 °C for these sites. MAAT at these sites range from −4.1 to −8.9 °C and the surface offsets vary from −1.1 to 3.9 °C. Estimated thermal offset range from −0.9 to 0 °C. Both statistical models show comparable results and suggest 95% mean permafrost cover in the catchment above 4727 m a.s.l. These results strongly indicate existence of significant permafrost areas across the high elevations of the cold-arid regions of IHR. So far, permafrost processes are not considered for assessing present and future estimates of water and regional climate and as a causative factor for disasters like debris flows and landslides in the region. This study highlight the need for greater research efforts on Himalayan permafrost to have a comprehensive understanding of Himalayan cryosphere. [ABSTRACT FROM AUTHOR]

• New hybrid thermal energy storage concept for storing steam and electrical energy. • Analysis by variation of number and properties of encasing phase change material. • 34% additional stored energy in steam storage with phase change material casing. • Analysis of a phase change material/metal arrangement with a dimensionless model. • Significant decrease of the melting time up to a metal volume fraction of 20%. In industrial processes, temporal differences between steam consumption and production can be compensated by integrating Ruths steam storage. The extension of a Ruths steam storage to a hybrid storage component by means of latent heat thermal energy storage with integrated electrical heating elements or heat exchangers was developed and is discussed in this paper. The latent heat thermal energy storage is arranged at the shell surface of the Ruths steam storage, which can be divided into chambers filled with different phase change materials. The aim of this concept is to create a flexible component with a high energy density, which can store thermal energy from steam, and surplus electrical energy or waste heat both short and long term. In this study, different hybrid storage arrangements are tested and analyzed. In the presented examples, the arrangement of one phase change material with a phase change temperature near the minimum inside the Ruths steam storage stores 34 % more energy than the Ruths steam storage without phase change material. For discharging, with 15 % additional provided energy the best obtained result is achieved with a phase change temperature near the maximum inside the Ruths steam storage vessel. The low thermal conductivity of most phase change materials may limit the performance of the hybrid storage component. Therefore, a layer arrangement of metal and phase change material for improving the heat transfer inside the phase change material of the hybrid storage is modeled and discussed. This method for heat transfer enhancement exhibits a significant decrease in melting time, with a metal fraction of up to 20 % and a ratio between the phase change material layer thickness and layer arrangement height of up to 1.5. [ABSTRACT FROM AUTHOR]

Abstract Objectives To investigate the feasibility of chemical exchange saturation transfer (CEST) MRI in patients with breast carcinomas and possible correlations between magnetization transfer asymmetry (MTR asym) values and histological features, such as tumor grade and the Ki-67 proliferation index. Materials and methods Nine healthy subjects and 18 female patients were enrolled for this study. The imaging protocol for the patients consisted of diffusion-weighted imaging (DWI), CEST imaging, and T1-weighted, contrast-enhanced (CE)-MRI. CEST was performed using a 3D gradient echo (GRE) sequence, employing eight pre-saturation pulses of a duration of 50 ms and a duty cycle (DC) of 80%, with a mean amplitude of the saturation pulse train of 1 μT. The Z-spectrum was plotted and MTR asym values calculated for the frequency of the maximum of MTR asym curve, were correlated with the Ki-67 proliferation index and apparent diffusion coefficient (ADC). Patient data were statistically assessed using the Games-Howell post-hoc and Pearson's correlation test. Results Different tumor types had asymmetry peaks at different positions of Z-spectrum. MTR asym (mean ± SD) (%) calculated for G1 (3.0 ± 0.3; range: 2.70–3.50) was not significantly lower than for G2 (4.50 ± 1.30; range: 3.20–6.50; p = 0.066). In contrast, the increase in MTR asym between G1 and G3 (6.40 ± 1.70; range: 4.80–9.80) lesions was significant (p = 0.007). No significant difference was observed between G2 and G3 with regard to MTR asym (p = 0.089). There was a strong positive correlation between the MTR asym , and Ki-67 proliferation index (r = 0.890; p = 0.001), while there was a moderate negative correlation between MTR asym and ADC values (r = −0.506; p = 0.027). Conclusions Calculated MTR asym demonstrates a strong positive correlation with tumor proliferation and has the potential to become a valuable biomarker for breast tumor characterization. [ABSTRACT FROM AUTHOR]

Abstract: Phosphorous (31P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3T and 7T. Six healthy volunteers were examined on a 3T and a 7T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (k ATP) and creatine kinase reaction (k CK), as well as corresponding metabolic fluxes (F ATP, F CK), were estimated. A comparison of these exchange parameters, apparent T 1s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7T was significantly higher (i.e., k ATP 2.7 times higher and k CK 3.4 times higher) than at 3T (p <0.05). The values for k ATP (p =0.35) and k CK (p =0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7T provided better data quality than did a 4 times-longer MT experiment at 3T. The minimal time-resolution to reliably quantify both F ATP and F CK at 7T was ∼6min. Our results show that MT experiments at 7T can be at least 4 times faster than 3T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7T. [Copyright &y& Elsevier]

Abstract: There is evidence that chronic pharmacoresistant temporal lobe epilepsy (TLE) is a progressive disorder accompanied by mental deterioration. We investigated effects of aging on cerebral N-acetyl-aspartate (NAA) concentrations in the temporal lobe of 12 patients with pharmacoresistant mesial TLE (mTLE) and 22 healthy controls by means of proton-magnetic resonance spectroscopy (1H-MRS) at 3 T. Furthermore, we calculated correlations between NAA concentrations and measures of verbal and figural memory in patients. In mTLE patients but not in healthy controls the concentration of NAA in the lateral temporal lobe was negatively correlated with age. In patients with mTLE NAA in left lateral temporal voxels correlated with verbal memory. NAA in medial temporal voxels did not correlate with age or neuropsychological measures. Significant decrease of NAA with age in the lateral temporal lobe of patients with mTLE provides evidence for progressive neuronal dysfunction with aging. NAA is a marker of neuronal integrity since it correlates with verbal memory. [Copyright &y& Elsevier]

Disjunction of maternal and paternal centromeres during meiosis I requires crossing over between homologous chromatids, which creates chiasmata that hold homologs together. It also depends on a mechanism ensuring that maternal and paternal sister kinetochore pairs attach to oppositely oriented microtubules. Proteolytic cleavage of cohesin''s Rec8 subunit by separase destroys cohesion between sister chromatid arms at anaphase I and thereby resolves chiasmata. The Spo12 and Slk19 proteins have been implicated in regulating meiosis I kinetochore orientation and/or in preventing cleavage of Rec8 at centromeres. We show here that the role of these proteins is instead to promote nucleolar segregation, including release of the Cdc14 phosphatase required for Cdk1 inactivation and disassembly of the anaphase I spindle. Separase is also required but surprisingly not its protease activity. It has two mechanistically different roles during meiosis I. Loss of the protease-independent function alone results in a second meiotic division occurring on anaphase I spindles in spo12Δ and slk19Δ mutants. [Copyright &y& Elsevier]