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Understanding the response of Himalayan glaciers to global warming is vital because of their role as a water source for the Asian subcontinent. However, great uncertainties still exist on the climate drivers of past and present glacier changes across scales. Here, we analyse continuous hourly climate station data from a glacierized elevation (Pyramid station, Mount Everest) since 1994 together with other ground observations and climate reanalysis. We show that a decrease in maximum air temperature and precipitation occurred during the last three decades at Pyramid in response to global warming. Reanalysis data suggest a broader occurrence of this effect in the glacierized areas of the Himalaya. We hypothesize that the counterintuitive cooling is caused by enhanced sensible heat exchange and the associated increase in glacier katabatic wind, which draws cool air downward from higher elevations. The stronger katabatic winds have also lowered the elevation of local wind convergence, thereby diminishing precipitation in glacial areas and negatively affecting glacier mass balance. This local cooling may have partially preserved glaciers from melting and could help protect the periglacial environment.

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.

Introduction: With the application of high-resolution 3D 7 Tesla Magnetic Resonance Spectroscopy Imaging (MRSI) in high-grade gliomas, we previously identified intratumoral metabolic heterogeneities. Methods: We prospectively included 36 patients with WHO 2021 grade 2–4 gliomas (20 IDH mutated, 16 IDH wildtype). Our 7 T 3D MRSI sequence provided high-resolution metabolic maps (e.g., choline, creatine, glutamine, and glycine) of these patients’ brains. We employed multivariate random forest and support vector machine models to voxels within a tumor segmentation, for classification of glioma grade and IDH mutation status. Results: Random forest analysis yielded an area under the curve (AUC) of 0.86 for multivariate IDH classification based on metabolic ratios. We distinguished high- and low-grade tumors by total choline (tCho) / total N-acetyl-aspartate (tNAA) ratio difference, yielding an AUC of 0.99. Tumor categorization based on other measured metabolic ratios provided comparable accuracy. Conclusions: We successfully classified IDH mutation status and high- versus low-grade gliomas preoperatively based on 7 T MRSI and clinical tumor segmentation. With this approach, we demonstrated imaging based tumor marker predictions at least as accurate as comparable studies, highlighting the potential application of MRSI for pre-operative tumor classifications.

MR spectroscopic imaging at 7.0 T can help visualize pathologic findings beyond demyelinating lesions in participants with multiple sclerosis; detected metabolic alterations in normal-appearing white matter and cortical gray matter were associated with disability.

Supplemental digital content is available in the text.

Supplemental digital content is available in the text.

The active layer plays a key role in geomorphic, hydrologic, and biogeochemical processes in permafrost regions. We conducted a systematic investigation of active layer thickness (ALT) in northeastern Qinghai‐Tibetan Plateau by using ground‐penetrating radar (GPR) with 100 and 200 MHz antennas. We used mechanical probing, pit, and soil temperature profiles for evaluating ALT derived from GPR. The results showed that GPR is competent for detecting ALT, and the error was ±0.08 m at common midpoint co‐located sites. Considerable spatial variability of ALT owing to variation in elevation, peat thickness, and slope aspect was found. The mean ALT was 1.32 ± 0.29 m with a range from 0.81 to 2.1 m in Eboling Mountain. In Yeniu Gou, mean ALT was 2.72 ± 0.88 m and varied from 1.07 m on the north‐facing slope to 4.86 m around the area near the lower boundary of permafrost. ALT in peat decreased with increasing elevation at rates of −1.31 m/km (Eboling Mountain) and −2.1 m/km (Yeniu Gou), and in mineral soil in Yeniu Gou, the rate changed to −4.18 m/km. At the same elevation, ALT on the south‐facing slope was about 0.8 m thicker than that on the north‐facing slopes, while the difference was only 0.18 m in peat‐covered area. Within a 100 m2area with a local elevation difference of 0.8 m, ALT varied from 0.68 m to 1.25 m. Both field monitoring and modeling studies on spatial ALT variations require rethinking of the current strategy and comprehensive design. GPR is competent and is a useful tool for the accurate and high‐resolution detection of active layer thickness in mountainous areasConsiderable spatial variability of active layer thickness was found owing to the variations in elevation, slope aspect, and peat layerChanges in active layer thickness were by greater than 80% within an area of 100 m2due solely to local microrelief of about 0.8 m

Quantitative sodium 23 MR imaging at 7 T, with 1.5-mm in-plane resolution, good image quality, and acceptable imaging time, is clinically feasible, may provide good differentiation between malignant and benign breast lesions, and demonstrates an inverse correlation with the apparent diffusion coefficient.

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 subtilischromosome. We demonstrate that targeting of Smc/ScpAB to ParB/parSloading 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 parSsites. 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.

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/parSpartition complexes. Whether SMC complexes recognize a specific DNA structure in the partition complex or a protein component is unclear. By replacing genes in Bacillus subtiliswith 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.

Multiparametric MR imaging of the breast with dynamic contrast-enhanced MR imaging and diffusion-weighted imaging at 7 T is feasible in clinical practice, seems to enable breast cancer diagnosis, and has high diagnostic accuracy (94.1% [44 of 46 lesions]) and excellent interrater agreement (κ = 0.833 to 1).

The purposes of this study were to introduce and assess an automated user-independent quantitative volumetric (AUQV) breast density (BD) measurement system on the basis of magnetic resonance imaging (MRI) using the Dixon technique as well as to compare it with qualitative and quantitative mammographic (MG) BD measurements.

The purpose of this study was to compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a single parameter to multiparametric (MP) MRI with 2 (DCE MRI and diffusion-weighted imaging DWI) and 3 (DCE MRI, DWI, and 3-dimensional proton magnetic resonance spectroscopic imaging 3D 1H-MRSI) parameters in breast cancer diagnosis.

The objective of this study was to compare the image quality, contrast enhancement behavior, and diagnostic value of bilateral 3-dimensional dynamic contrast-enhanced breast magnetic resonance imaging (MRI), with high spatial and temporal resolution, at 3 and 7 T, in the same patient group.

Abstract: Due to a lack of systematic observations, the intensity and volume of rock falls and rock avalanches in high mountain areas are still poorly known. Nevertheless, these phenomena could have burly consequences. To document present rock falls, a network of observers (guides, mountaineers, and hut wardens) was initiated in the Mont Blanc Massif in 2005 and became fully operational in 2007. This article presents data on the 66 rock falls (100 m3 ≤ V ≤ 50,000 m3) documented in 2007 (n = 41) and 2008 (n = 25). Most of the starting zones are located in warm permafrost areas, which are most sensitive to warming, and only four rock falls are clearly out of permafrost area. Different elements support permafrost degradation as one of the main triggering factors of present rock falls in high mountain areas.

To develop a 3.0 Tesla breast imaging protocol that combines high temporal and spatial resolution three-dimensional MR sequences for quantitative time course and morphologic analysis of breast lesions.

We sought to retrospectively investigate differences in correlation of absolute metabolites concentrations and metabolite ratios with histopathologic parameters of stereotactic biopsies from the border zone of gliomas.

This study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla.

In a systematic study on the interdependence of linewidth, signal-to-noise ratio (SNR), and spatial resolution in 3D proton spectroscopic imaging (¹H-SI) at 3 T, we demonstrate reduced linewidths with increased spatial resolution due to reduced magnetic inhomogeneity within the brain. High-precision quantitative data (0.75–0.094 cm³) were obtained for all resolutions, enabling the creation of metabolic maps that display details such as the ventricles, sulci, and gyri. High-resolution ¹H-SI allows differences in metabolic ratios to be estimated for anatomically defined regions in gray (GM) and white matter (WM). Seven distinct regions in a healthy brain were anatomically segmented and their metabolic ratios were compared quantitatively. Data from a tumor patient are also presented to demonstrate potential clinical applications. Because of the high resolution, the metabolite ratios could be determined for distinct pathologic regions within the tumor and its surroundings. The method was additionally applied to a patient with patchy Pelizaeus Merzbacher disease (PMD), and compared to single-voxel spectroscopy performed in the same session. High-resolution SI data were demonstrated in our study to allow the direct matching of anatomic and metabolic images. This may enhance the clinical value of ¹H-SI. Magn Reson Med 49:299–306, 2003. © 2003 Wiley-Liss, Inc.

In a systematic study on the interdependence of linewidth, signal‐to‐noise ratio (SNR), and spatial resolution in 3D proton spectroscopic imaging (1H‐SI) at 3 T, we demonstrate reduced linewidths with increased spatial resolution due to reduced magnetic inhomogeneity within the brain. High‐precision quantitative data (0.75–0.094 cm3) were obtained for all resolutions, enabling the creation of metabolic maps that display details such as the ventricles, sulci, and gyri. High‐resolution 1H‐SI allows differences in metabolic ratios to be estimated for anatomically defined regions in gray (GM) and white matter (WM). Seven distinct regions in a healthy brain were anatomically segmented and their metabolic ratios were compared quantitatively. Data from a tumor patient are also presented to demonstrate potential clinical applications. Because of the high resolution, the metabolite ratios could be determined for distinct pathologic regions within the tumor and its surroundings. The method was additionally applied to a patient with patchy Pelizaeus Merzbacher disease (PMD), and compared to single‐voxel spectroscopy performed in the same session. High‐resolution SI data were demonstrated in our study to allow the direct matching of anatomic and metabolic images. This may enhance the clinical value of 1H‐SI. Magn Reson Med 49:299–306, 2003. © 2003 Wiley‐Liss, Inc.

In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented dl sodium β-hydroxybutyrate (β-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95%) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of β-OHB increased to levels comparable to a 16- to 24-h fast while on dl sodium β-OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of β-OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of β-OHB to acetoacetate indicated exogenous origin of β-OHB. An increase of intracerebral concentrations of β-OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral dl sodium β-OHB was tolerated without side effects. This first report on oral supplementation of dl sodium β-OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood–brain barrier and could provide the basis for further evaluation of the neuroprotective effect of β-OHB in conditions with hypoketotic hypoglycemia.

In persistent hyperinsulinemic hypoglycemia of infancy, ketone body concentrations are abnormally low at times of hypoglycemia, depriving the brain of its most important alternative fuel. The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited. Assuming that exogenous ketone body compounds as a dietetic food might replace this alternative energy source for the brain, we have monitored the fate of orally supplemented dl sodium -hydroxybutyrate (-OHB) in two 6-mo-old infants with persistent hyperinsulinemic hypoglycemia for 5 and 7 mo, while on frequent tube-feedings and treatment with octreotide. Near total (95) pancreatectomy had been ineffective in one patient and was refused in the other. In blood, concentrations of -OHB increased to levels comparable to a 16- to 24-h fast while on dl sodium -OHB 880 to 1000 mg/kg per day. In cerebrospinal fluid, concentrations of -OHB increased to levels comparable to a 24- to 40-h fast, after single dosages of 4 and 8 g, respectively. High ratios of -OHB to acetoacetate indicated exogenous origin of -OHB. An increase of intracerebral concentrations of -OHB could be demonstrated by repetitive single-voxel proton magnetic resonance spectroscopy by a clear doublet at 1.25 ppm. Oral dl sodium -OHB was tolerated without side effects. This first report on oral supplementation of dl sodium -OHB in two patients with persistent hyperinsulinemic hypoglycemia demonstrates effective uptake across the blood–brain barrier and could provide the basis for further evaluation of the neuroprotective effect of -OHB in conditions with hypoketotic hypoglycemia.

Longitudinal and transverse relaxation times were measured for proton MRS signals from human brain metabolites at 3 T using a short‐echo STEAM protocol and a surface coil as a transmitter/receiver. Volumes of interest containing mostly grey or mostly white matter were selected in occipital lobes of healthy subjects and relaxation times for the following resonances were obtained: N‐acetylaspartate at 2.01 ppm (T1and T2), glutamate at 2.35 ppm (T1), creatine at 3.03 and 3.92 ppm (T1and T2), choline‐containing substances at 3.22 ppm (T1and T2), myo‐inositol at 3.57 and 3.65 ppm (T1) and the overlapping signals of glutamate and glutamine at 3.75 ppm (T1). The T1relaxation times obtained range from 0.97 to 1.47 s for grey matter and from 0.87 to 1.35 s for white matter. On the other hand, T2relaxation times range from 116 to 247 ms and from 141 to 295 ms in grey and white matter, respectively. Generally, the T1values measured at 3 T are close to the previously published data found at 1.5, 2 and 4.1 T. Also, the T2values confirm the previously observed decrease in transverse relaxation times with increasing static magnetic field. The proton relaxation times obtained will allow improved sequence design and spectra quantitation at 3 T, currently tested for enhanced clinical applications. Copyright © 2001 John Wiley & Sons, Ltd.

Longitudinal and transverse relaxation times were measured for proton MRS signals from human brain metabolites at 3 T using a short-echo STEAM protocol and a surface coil as a transmitter/receiver. Volumes of interest containing mostly grey or mostly white matter were selected in occipital lobes of healthy subjects and relaxation times for the following resonances were obtained: N-acetylaspartate at 2.01 ppm (T1 and T2), glutamate at 2.35 ppm (T1), creatine at 3.03 and 3.92 ppm (T1 and T2), choline-containing substances at 3.22 ppm (T1 and T2), myo-inositol at 3.57 and 3.65 ppm (T1) and the overlapping signals of glutamate and glutamine at 3.75 ppm (T1). The T1 relaxation times obtained range from 0.97 to 1.47 s for grey matter and from 0.87 to 1.35 s for white matter. On the other hand, T2 relaxation times range from 116 to 247 ms and from 141 to 295 ms in grey and white matter, respectively. Generally, the T1 values measured at 3 T are close to the previously published data found at 1.5, 2 and 4.1 T. Also, the T2 values confirm the previously observed decrease in transverse relaxation times with increasing static magnetic field. The proton relaxation times obtained will allow improved sequence design and spectra quantitation at 3 T, currently tested for enhanced clinical applications. Copyright © 2001 John Wiley & Sons, Ltd.

Field mapping of mountain permafrost is laborious and is generally based on interpolation between point information. A spatial model that is based on elevation and a parameterization of solar radiation during summer is presented here. It allows estimation of permafrost distribution and can be calibrated locally, based on bottom temperature of snow (BTS) measurements or other indicators such as mapped features of permafrost creep. Local calibration makes this approach flexible and allows application in various mountain ranges. Model output consists of a continuous field of simulated BTS values that are subsequently divided into the classes ‘permafrost likely’, ‘permafrost possible’ and ‘no permafrost’ following the rules of thumb established for BTS field measurements in the Alps. Additionally, the simulated BTS values can be interpreted as a crude proxy for ground temperature regime and sensitivity to permafrost degradation. A map of vegetation abundance derived from atmospherically and topographically corrected satellite imagery was incorporated into this model to enhance the accuracy of the prediction. Based on the same corrected satellite image, a map of albedo was derived and used to calculate net short-wave radiation, in an attempt to increase model accuracy. However, the statistical relationship with BTS did not improve. This is probably due to the correlation of short-wave solar radiation with snow-melt patterns or other factors of permafrost distribution which are being influenced differently by the introduction of albedo. Copyright © 2001 John Wiley & Sons, Ltd. La cartographie sur le terrain du pergélisol de montagne est un travail laborieux généralement basé e sur des interpolations entre des points pour lesquelles on possède des informations. Un modèle spatial basé sur l'altitude et le calcul de la radiation solaire est présenté ici. Il permet d'estimer la distribution du pergélisol et peut être calibré localement en utilisant des mesures de température à la base de la neige (BTS) et d'autres indications comme celles résultant de la cartographie des traces de creep du pergélisol. Une calibration locale rend cette approche flexible et permet son application dans différents milieux montagneux. Les données provenant du modèle se présentent comme un champ continu de valeurs BTS simulées qui sont par la suite divisées en classes de “pergélisol probable”, “pergélisol possible” et “pergélisol absent” suivant une règle empirique établie pour les mesures BTS dans les Alpes. En outre, les valeurs BTS simulées peuvent être interprétées comme donnant une approximation du régime de température du sol et de la fragilité à la dégradation du pergélisol. Une carte de l'abondance de la végétation dérivée d'images satellitaires corrigées pour l'atmosphère et la topographie a été incorporée dans ce modèle dans l'espoir d'augmenter la précision de la prédiction. Basée sur la même image satellitaire corrigée, une carte de l'albedo a été obtenue et utilisée pour calculer la radiation nette dans les ondes courtes pour essayer d'augmenter encore la précision du modèle. Toutefois la relation statistique avec les résultats obtenus par BTS n'a pas été augmentée. Cela est probablement dû à la corrélation existante entre la radiation solaire à courte longueur d'onde et le réseaux de fonte des neige, ainsi qu'à d'autres facteurs qui contrôlent la distribution du pergélisol en variant différemment d e l'albedo. Copyright © 2001 John Wiley & Sons, Ltd.

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 subtilisSmc-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.

ABSTRACTParB proteins bind centromere-like DNA sequences called parSsites and are involved in plasmid and chromosome segregation in bacteria. We previously showed that the opportunistic human pathogen Streptococcus pneumoniaecontains four parSsequences located close to the origin of replication which are bound by ParB. Using chromatin immunoprecipitation (ChIP), we found here that ParB spreads out from one of these parSsites, parS(−1.6°), for more than 5 kb and occupies the nearby comCDEoperon, which drives competence development. Competence allows S. pneumoniaeto take up DNA from its environment, thereby mediating horizontal gene transfer, and is also employed as a general stress response. Mutating parS(−1.6°) or deleting parBresulted in transcriptional up-regulation of comCDEand ssbB(a gene belonging to the competence regulon), demonstrating that ParB acts as a repressor of competence. However, genome-wide transcription analysis showed that ParB is not a global transcriptional regulator. Different factors, such as the composition of the growth medium and antibiotic-induced stress, can trigger the sensitive switch driving competence. This work shows that the ParB-parSchromosome segregation machinery also influences this developmental process.IMPORTANCEStreptococcus pneumoniae(pneumococcus) is an important human pathogen responsible for more than a million deaths each year. Like all other organisms, S. pneumoniaemust be able to segregate its chromosomes properly. Not only is understanding the molecular mechanisms underlying chromosome segregation in S. pneumoniaetherefore of fundamental importance, but also, this knowledge might offer new leads for ways to target this pathogen. Here, we identified a link between the pneumococcal chromosome segregation system and the competence-developmental system. Competence allows S. pneumoniaeto take up and integrate exogenous DNA in its chromosome. This process plays a crucial role in successful adaptation to—and escape from—host defenses, antibiotic treatments, and vaccination strategies. We show that the chromosome segregation protein ParB acts as a repressor of competence. To the best of our knowledge, this is the first example of a ParB protein controlling bacterial competence.