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result(s) for
"Gruber, Stephan"
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Ground subsidence and heave over permafrost: hourly time series reveal interannual, seasonal and shorter-term movement caused by freezing, thawing and water movement
2020
Heave and subsidence of the ground surface can offer insight into processes of heat and mass transfer in freezing and thawing soils. Additionally, subsidence is an important metric for monitoring and understanding the transformation of permafrost landscapes under climate change. Corresponding ground observations, however, are sparse and episodic. A simple tilt-arm apparatus with logging inclinometer has been developed to measure heave and subsidence of the ground surface with hourly resolution and millimeter accuracy. This contribution reports data from the first two winters and the first full summer, measured at three sites with contrasting organic and frost-susceptible soils in warm permafrost. The patterns of surface movement differ significantly between sites and from a prediction based on the Stefan equation and observed ground temperature. The data are rich in features of heave and subsidence that are several days to several weeks long and that may help elucidate processes in the ground. For example, late-winter heave followed by thawing and subsidence, as reported in earlier literature and hypothesized to be caused by infiltration and refreezing of water into permeable frozen ground, has been detected. An early-winter peak in heave, followed by brief subsidence, is discernible in a previous publication but so far has not been interpreted. An effect of precipitation on changes in surface elevation can be inferred with confidence. These results highlight the potential of ground-based observation of subsidence and heave as an enabler of progress in process understanding, modeling and interpretation of remotely sensed data.
Journal Article
DNA segment capture by Smc5/6 holocomplexes
2023
Three distinct structural maintenance of chromosomes (SMC) complexes facilitate chromosome folding and segregation in eukaryotes, presumably by DNA loop extrusion. How SMCs interact with DNA to extrude loops is not well understood. Among the SMC complexes, Smc5/6 has dedicated roles in DNA repair and preventing a buildup of aberrant DNA junctions. In the present study, we describe the reconstitution of ATP-dependent DNA loading by yeast Smc5/6 rings. Loading strictly requires the Nse5/6 subcomplex which opens the kleisin neck gate. We show that plasmid molecules are topologically entrapped in the kleisin and two SMC subcompartments, but not in the full SMC compartment. This is explained by the SMC compartment holding a looped DNA segment and by kleisin locking it in place when passing between the two flanks of the loop for neck-gate closure. Related segment capture events may provide the power stroke in subsequent DNA extrusion steps, possibly also in other SMC complexes, thus providing a unifying principle for DNA loading and extrusion.
Here, the authors biochemically demonstrate how the Smc5/6 SMC compartment holds a DNA loop by topologically entrapping DNA in two SMC subcompartments and the kleisin compartment. This mechanism requires the Nse5/6 loader to open the neck gate before DNA entrance.
Journal Article
Kinematics of steep bedrock permafrost
by
Gruber, Stephan
,
Hasler, Andreas
,
Beutel, Jan
in
bedrock permafrost
,
climate change impact
,
Cryosphere
2012
The mechanisms that control climate‐dependent rockfall from permafrost mountain slopes are currently poorly understood. In this study, we present the results of an extensive rock slope monitoring campaign at the Matterhorn (Switzerland) with a wireless sensor network. A negative dependency of cleft expansion relative to temperature was observed at all clefts for the dominant part of the year. At many clefts this process is interrupted by a period with increased opening and shearing activity in the summer months. More specific, this period lasts from sustained melting within the cleft to the first freezing in autumn. Based on these empirical findings we identify two distinct process regimes governing the cleft motion observed. Combining current theories with laboratory evidence on rock slope movement and stability, we postulate that (1) the negative temperature‐dependency is caused by thermomechanical forcing and is reinforced by cryogenic processes during the freezing period and, (2) the enhanced movement in summer originates from a hydro‐thermally induced strength reduction in clefts containing perennial ice. It can be assumed that the irreversible part of the process described in (1) slowly modifies the geometric settings and cleft characteristics of permafrost rock slopes in the long term. The thawing related processes (2) can affect stability within hours or weeks. Such short‐term stability minima may activate rock masses subject to the slow changes and lead to acceleration and failure. Key Points Novel in‐situ measurements of rock movements in steep permafrost Two seasonally separated temperature dependent movement regimes Enhanced summer movements may indicate instabilities
Journal Article
VirB, a transcriptional activator of virulence in Shigella flexneri, uses CTP as a cofactor
2023
VirB is a transcriptional activator of virulence in the gram-negative bacterium
Shigella flexneri
encoded by the large invasion plasmid, pINV. It counteracts the transcriptional silencing by the nucleoid structuring protein, H-NS. Mutations in
virB
lead to loss of virulence. Studies suggested that VirB binds to specific DNA sequences, remodels the H-NS nucleoprotein complexes, and changes DNA supercoiling. VirB belongs to the superfamily of ParB proteins which are involved in plasmid and chromosome partitioning often as part of a ParABS system. Like ParB, VirB forms discrete foci in
Shigella flexneri
cells harbouring pINV. Our results reveal that purified preparations of VirB specifically bind the ribonucleotide CTP and slowly but detectably hydrolyse it with mild stimulation by the
virS
targeting sequences found on pINV. We show that formation of VirB foci in cells requires a
virS
site and CTP binding residues in VirB. Curiously, DNA stimulation of clamp closure appears efficient even without a
virS
sequence in vitro. Specificity for entrapment of
virS
DNA is however evident at elevated salt concentrations. These findings suggest that VirB acts as a CTP-dependent DNA clamp and indicate that the cellular microenvironment contributes to the accumulation of VirB specifically at
virS
sites.
This study sheds light on the mechanism of transcription activation by which VirB, a virulence transcription activator in
Shigella flexneri
, the causative agent of the diarrheal disease shigellosis, uses the ribonucleotide CTP as a cofactor to load at specific DNA sites.
Journal Article
Connecting the dots: key insights on ParB for chromosome segregation from single-molecule studies
by
Tišma, Miloš
,
Gruber, Stephan
,
Le, Tung B K
in
Atomic force microscopy
,
Bacterial Proteins - genetics
,
Bacterial Proteins - metabolism
2024
Bacterial cells require DNA segregation machinery to properly distribute a genome to both daughter cells upon division. The most common system involved in chromosome and plasmid segregation in bacteria is the ParABS system. A core protein of this system - partition protein B (ParB) - regulates chromosome organization and chromosome segregation during the bacterial cell cycle. Over the past decades, research has greatly advanced our knowledge of the ParABS system. However, many intricate details of the mechanism of ParB proteins were only recently uncovered using in vitro single-molecule techniques. These approaches allowed the exploration of ParB proteins in precisely controlled environments, free from the complexities of the cellular milieu. This review covers the early developments of this field but emphasizes recent advances in our knowledge of the mechanistic understanding of ParB proteins as revealed by in vitro single-molecule methods. Furthermore, we provide an outlook on future endeavors in investigating ParB, ParB-like proteins, and their interaction partners.
A review highlighting insights from single-molecule studies on ParB, the key organizing protein that mediates DNA condensation and segregation.
Journal Article
Closing the cohesin ring: Structure and function of its Smc3-kleisin interface
by
Petela, Naomi
,
Beckouët, Frédéric
,
Gruber, Stephan
in
Acetylation
,
Adenosine triphosphatase
,
Adenosine triphosphatases
2014
Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two α helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.
Journal Article
Modelling the temporal dynamics of subarctic surface temperature inversions from atmospheric reanalysis for producing point-scale multi-decade meteorological time series in mountains
2025
The vertical profile of air temperatures in subarctic regions is difficult to quantify, especially in areas with mountainous terrain subject to strong and lasting inversion events. Relying on observational data is not possible in most places due to sparse weather stations. To address this gap, we use reanalysis data to produce a model of the inversion strength. This model uses a single downscaled atmospheric column from reanalysis data and is calibrated with five weather stations close to Dawson City, Yukon, situated at various elevations. It is shown to perform better than bare reanalysis products and its parameters take into account the observed long-term decrease in frequency, strength, and depth of inversions since 1948, departing from the pattern of elevation-dependent warming found in lower latitude mountain regions. Once calibrated, the model only relies on global reanalysis data and hence can be applied in the vicinity of the calibration site, even where no observational data are available. Producing reliable time series for air temperature in complex terrain where inversions are strong and frequent is essential in modelling permafrost and understanding its future evolution. This model uses ever-improving physically based data, making it future-proof and versatile in its regional applications.
Journal Article
The SMC Hinge is a Selective Gate for Obstacle Bypass
by
Srinivasan, Madhusudhan
,
Gruber, Stephan
,
Taschner, Michael
in
631/45/147
,
631/535
,
631/57/2272
2025
DNA loop-extruding SMC complexes play vital roles in genome maintenance and DNA immunity. However, how these ring-shaped DNA motors navigate large DNA-bound obstacles has remained unclear. Here, we demonstrate that a bacterial SMC Wadjet complex can efficiently bypass obstacles larger than the SMC coiled coil lumen when they are tethered to the extruded DNA by a single-stranded DNA or RNA linker. This bypass is mediated by the selective entrapment of the linker within the SMC hinge channel, which functions as an obligate gate—permitting passage of the linker while retaining double-stranded DNA stably inside the SMC ring and keeping associated obstacles outside. We further show that eukaryotic SMC hinges similarly accommodate ssDNA, and that the hinge is dispensable for loop extrusion by Wadjet, altogether suggesting that obstacle bypass represents the conserved, long-sought function of the SMC hinge toroid. By integrating hinge bypass with loop extrusion, we provide a mechanistic framework for how DNA-entrapping SMC complexes can generate chromosomal loops densely decorated with obstacles.
SMC complexes are ring-shaped motors that fold DNA by extruding loops, but how they navigate large DNA obstacles is unclear. Here, Liu et al., show that SMC complexes bypass obstacles by threading obstacle linkers through a selective hinge channel, enabling translocation on crowded chromatin.
Journal Article
Review article: Inferring permafrost and permafrost thaw in the mountains of the Hindu Kush Himalaya region
by
Schmid, Marc-Olivier
,
Zhang, Yinsheng
,
Gruber, Stephan
in
Climate
,
Climate change
,
Cryosphere
2017
The cryosphere reacts sensitively to climate change, as evidenced by the widespread retreat of mountain glaciers. Subsurface ice contained in permafrost is similarly affected by climate change, causing persistent impacts on natural and human systems. In contrast to glaciers, permafrost is not observable spatially and therefore its presence and possible changes are frequently overlooked. Correspondingly, little is known about permafrost in the mountains of the Hindu Kush Himalaya (HKH) region, despite permafrost area exceeding that of glaciers in nearly all countries. Based on evidence and insight gained mostly in other permafrost areas globally, this review provides a synopsis on what is known or can be inferred about permafrost in the mountains of the HKH region. Given the extreme nature of the environment concerned, it is to be expected that the diversity of conditions and phenomena encountered in permafrost exceed what has previously been described and investigated. We further argue that climate change in concert with increasing development will bring about diverse permafrost-related impacts on vegetation, water quality, geohazards, and livelihoods. To better anticipate and mitigate these effects, a deepened understanding of high-elevation permafrost in subtropical latitudes as well as the pathways interconnecting environmental changes and human livelihoods are needed.
Journal Article
Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct (2H) and indirect (1H) detection of deuterium labeled compounds at 7T and clinical 3T
by
Strasser, Bernhard
,
Gruber, Stephan
,
Hingerl, Lukas
in
Alzheimer's disease
,
Automation
,
Brain - diagnostic imaging
2023
•Imaging of brain glucose metabolism using MR spectroscopic imaging and 2H labeling.•Direct (2H DMI at 7T) and indirect detection (1H QELT at 3T) were compared.•Comparable enrichment of labeled compounds was observed with both methods.•Reproduced 7T DMI results using 1H QELT at clinical 3T without additional hardware.
Deuterium metabolic imaging (DMI) and quantitative exchange label turnover (QELT) are novel MR spectroscopy techniques for non-invasive imaging of human brain glucose and neurotransmitter metabolism with high clinical potential. Following oral or intravenous administration of non-ionizing [6,6′-2H2]-glucose, its uptake and synthesis of downstream metabolites can be mapped via direct or indirect detection of deuterium resonances using 2H MRSI (DMI) and 1H MRSI (QELT), respectively. The purpose of this study was to compare the dynamics of spatially resolved brain glucose metabolism, i.e., estimated concentration enrichment of deuterium labeled Glx (glutamate+glutamine) and Glc (glucose) acquired repeatedly in the same cohort of subjects using DMI at 7T and QELT at clinical 3T.
Five volunteers (4 m/1f) were scanned in repeated sessions for 60 min after overnight fasting and 0.8 g/kg oral [6,6′-2H2]-glucose administration using time-resolved 3D 2H FID-MRSI with elliptical phase encoding at 7T and 3D 1H FID-MRSI with a non-Cartesian concentric ring trajectory readout at clinical 3T.
One hour after oral tracer administration regionally averaged deuterium labeled Glx4 concentrations and the dynamics were not significantly different over all participants between 7T 2H DMI and 3T 1H QELT data for GM (1.29±0.15 vs. 1.38±0.26 mM, p=0.65 & 21±3 vs. 26±3 µM/min, p=0.22) and WM (1.10±0.13 vs. 0.91±0.24 mM, p=0.34 & 19±2 vs. 17±3 µM/min, p=0.48). Also, the observed time constants of dynamic Glc6 data in GM (24±14 vs. 19±7 min, p=0.65) and WM (28±19 vs. 18±9 min, p=0.43) dominated regions showed no significant differences. Between individual 2H and 1H data points a weak to moderate negative correlation was observed for Glx4 concentrations in GM (r=-0.52, p<0.001), and WM (r=-0.3, p<0.001) dominated regions, while a strong negative correlation was observed for Glc6 data GM (r=-0.61, p<0.001) and WM (r=-0.70, p<0.001).
This study demonstrates that indirect detection of deuterium labeled compounds using 1H QELT MRSI at widely available clinical 3T without additional hardware is able to reproduce absolute concentration estimates of downstream glucose metabolites and the dynamics of glucose uptake compared to 2H DMI data acquired at 7T. This suggests significant potential for widespread application in clinical settings especially in environments with limited access to ultra-high field scanners and dedicated RF hardware.
Journal Article