Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

Grass-Shrub Associations over a Precipitation Gradient and Their Implications for Restoration in the Great Basin,USA

As environmental stress increases positive (facilitative) plant interactions often predominate. Plant-plant associations (or lack thereof) can indicate whether certain plant species favor particular types of microsites (e.g., shrub canopies or plant-free interspaces) and can provide valuable insights into whether “nurse plants” will contribute to seeding or planting success during ecological restoration. It can be difficult, however, to anticipate how relationships between nurse plants and plants used for restoration may change over large-ranging, regional stress gradients. We investigated associations between the shrub, Wyoming big sagebrush (Artemisia tridentata ssp. wyomingensis), and three common native grasses (Poa secunda, Elymus elymoides, and Pseudoroegneria spicata), representing short-, medium-, and deep-rooted growth forms, respectively, across an annual rainfall gradient (220–350 mm) in the Great Basin, USA. We hypothesized that positive shrub-grass relationships would become more frequent at lower rainfall levels, as indicated by greater cover of grasses in shrub canopies than vegetation-free interspaces. We sampled aerial cover, density, height, basal width, grazing status, and reproductive status of perennial grasses in canopies and interspaces of 25–33 sagebrush individuals at 32 sites along a rainfall gradient. We found that aerial cover of the shallow rooted grass, P. secunda, was higher in sagebrush canopy than interspace microsites at lower levels of rainfall. Cover and density of the medium-rooted grass, E. elymoides were higher in sagebrush canopies than interspaces at all but the highest rainfall levels. Neither annual rainfall nor sagebrush canopy microsite significantly affected P. spicata cover. E. elymoides and P. spicata plants were taller, narrower, and less likely to be grazed in shrub canopy microsites than interspaces. Our results suggest that exploring sagebrush canopy microsites for restoration of native perennial grasses might improve plant establishment, growth, or survival (or some combination thereof), particularly in drier areas. We suggest that land managers consider the nurse plant approach as a way to increase perennial grass abundance in the Great Basin. Controlled experimentation will provide further insights into the life stage-specific effectiveness and practicality of a nurse plant approach for ecological restoration in this region.     

Direct Measurements of Drag Forces in C. elegans Crawling Locomotion

With a simple and versatile microcantilever-based force measurement technique, we have probed the drag forces involved in Caenorhabditis elegans locomotion. As a worm crawls on an agar surface, we found that substrate viscoelasticity introduces nonlinearities in the force-velocity relationships, yielding nonconstant drag coefficients that are not captured by original resistive force theory. A major contributing factor to these nonlinearities is the formation of a shallow groove on the agar surface. We measured both the adhesion forces that cause the worm’s body to settle into the agar and the resulting dynamics of groove formation. Furthermore, we quantified the locomotive forces produced by C. elegans undulatory motions on a wet viscoelastic agar surface. We show that an extension of resistive force theory is able to use the dynamics of a nematode’s body shape along with the measured drag coefficients to predict the forces generated by a crawling nematode.     

PKA phosphorylates and inactivates AMPKα to promote efficient lipolysis

The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by β‐adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormone‐sensitive lipase (HSL). TAG resynthesis is associated with high‐energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA‐mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKα1 at Ser‐173 to impede threonine (Thr‐172) phosphorylation and thus activation of AMPKα1 by LKB1 in response to lipolytic signals. Activation of AMPKα1 by LKB1 is also blocked by PKA‐mediated phosphorylation of AMPKα1 in vitro. Functional analysis of an AMPKα1 species carrying a non‐phosphorylatable mutation at Ser‐173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKA‐activating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response.     

An Integrated Approach to Modeling Grazing Pressure in Pastoral Systems: The Case of the Logone Floodplain (Cameroon)

The discussion about the impact of pastoral systems on ecosystems has been profoundly shaped by Hardin’s “tragedy of the commons” argument that held pastoralists responsible for overgrazing the range. Recent studies have shown that grazing ecosystems are much more complex and dynamic than was previously assumed and that pastoralists adaptively manage these systems. However, we still have little understanding how everyday herding affects ecosystems at the landscape level. We conducted a study of daily herd movements and grazing strategies in a mobile pastoral system in the Logone floodplain, Cameroon. We integrated GPS/GIS technology, video recordings of animal behavior, and ethnographic methods to develop a more accurate measurement of grazing pressure that takes into account both livestock densities and grazing behavior. We used the resulting grazing pressure data to evaluate existing conceptual models of grazing pressure at a landscape level. We found that models that predict that grazing pressure is skewed towards the direction of water most accurately reflect the situation in the Logone floodplain in the dry season. However, we found that the higher grazing pressure is not only the result of a higher density of cattle but also a change in the grazing behavior of animals after watering. Finally, we caution that the models of grazing pressure in the dry season cannot simply be extrapolated to the landscape level because mobile pastoralists do not remain in one central place.     

Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10⁻¹⁰). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10⁻²³) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10⁻¹⁷) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10⁻⁶), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10⁻⁵).     

Muscle use during double poling evaluated by positron emission tomography

Due to the complexity of movement in cross-country skiing (XCS), the muscle activation patterns are not well elucidated. Previous studies have applied surface electromyography (SEMG); however, recent gains in three-dimensional (3D) imaging techniques such as positron emission tomography (PET) have rendered an alternative approach to investigate muscle activation. The purpose of the present study was to examine muscle use during double poling (DP) at two work intensities by use of PET. Eight male subjects performed two 20-min DP bouts on separate days. Work intensity was ～ 53 and 74% of peak oxygen uptake (Vo(2peak)), respectively. During exercise 188 ± 8 MBq of [(18)F]fluorodeoxyglucose ([(18)F]FDG) was injected, and subsequent to exercise a full-body PET scan was conducted. Regions of interest (ROI) were defined within 15 relevant muscles, and a glucose uptake index (GUI) was determined for all ROIs. The muscles that span the shoulder and elbow joints, the abdominal muscles, and hip flexors displayed the greatest GUI during DP. Glucose uptake did not increase significantly from low to high intensity in most upper body muscles; however, an increased GUI (P < 0.05) was seen for the knee flexor (27%) and extensor muscles (16%), and for abdominal muscles (21%). The present data confirm previous findings that muscles of the upper limb are the primary working muscles in DP. The present data further suggest that when exercise intensity increases, the muscles that span the lumbar spine, hip, and knee joints contribute increasingly. Finally, PET provides a promising alternative or supplement to existing methods to assess muscle activation in complex human movements.     

Squeezing and detachment of living cells

The interaction of living cells with their environment is linked to their adhesive and elastic properties. Even if the mechanics of simple lipid membranes is fairly well understood, the analysis of single cell experiments remains challenging in part because of the mechanosensory response of cells to their environment. To study the mechanical properties of living cells we have developed a tool that borrows from micropipette aspiration techniques, atomic force microscopy, and the classical Johnson-Kendall-Roberts test. We show results from a study of the adhesion properties of living cells, as well as the elastic response and relaxation. We present models that are applied throughout the different stages of an experiment, which indicate that the contribution of the different components of the cell are active at various stages of compression, retraction, and detachment. Finally, we present a model that attempts to elucidate the surprising logarithmic relaxation observed when the cell is subjected to a given deformation.