Bending It Like Beckham: How to Visually Fool the Goalkeeper

As bending free-kicks becomes the norm in modern day soccer, implications for goalkeepers have largely been ignored. Although it has been reported that poor sensitivity to visual acceleration makes it harder for expert goalkeepers to perceptually judge where the curved free-kicks will cross the goal line, it is unknown how this affects the goalkeeper's actual movements.Here, an in-depth analysis of goalkeepers' hand movements in immersive, interactive virtual reality shows that they do not fully account for spin-induced lateral ball acceleration. Hand movements were found to be biased in the direction of initial ball heading, and for curved free-kicks this resulted in biases in a direction opposite to those necessary to save the free-kick. These movement errors result in less time to cover a now greater distance to stop the ball entering the goal. These and other details of the interceptive behaviour are explained using a simple mathematical model which shows how the goalkeeper controls his movements online with respect to the ball's current heading direction. Furthermore our results and model suggest how visual landmarks, such as the goalposts in this instance, may constrain the extent of the movement biases.While it has previously been shown that humans can internalize the effects of gravitational acceleration, these results show that it is much more difficult for goalkeepers to account for spin-induced visual acceleration, which varies from situation to situation. The limited sensitivity of the human visual system for detecting acceleration, suggests that curved free-kicks are an important goal-scoring opportunity in the game of soccer

TREM1/3 deficiency impairs tissue repair after acute kidney injury and mitochondrial metabolic flexibility in tubular epithelial cells

Long-term sequelae of acute kidney injury (AKI) are associated with incomplete recovery of renal function and the development of chronic kidney disease (CKD), which can be mediated by aberrant innate immune activation, mitochondrial pathology, and accumulation of senescent tubular epithelial cells (TECs). Herein, we show that the innate immune receptor Triggering receptor expressed on myeloid cells-1 (TREM-1) links mitochondrial metabolism to tubular epithelial senescence. TREM-1 is expressed by inflammatory and epithelial cells, both players in renal repair after ischemia/reperfusion (IR)-induced AKI. Hence, we subjected WT and TREM1/3 KO mice to different models of renal IR. TREM1/3 KO mice displayed no major differences during the acute phase of injury, but increased mortality was observed in the recovery phase. This detrimental effect was associated with maladaptive repair, characterized by persistent tubular damage, inflammation, fibrosis, and TEC senescence. In vitro, we observed an altered mitochondrial homeostasis and cellular metabolism in TREM1/3 KO primary TECs. This was associated with G2/M arrest and increased ROS accumulation. Further exposure of cells to ROS-generating triggers drove the cells into a stress-induced senescent state, resulting in decreased wound healing capacity. Treatment with a mitochondria anti-oxidant partly prevented the senescent phenotype, suggesting a role for mitochondria herein. In summary, we have unraveled a novel (metabolic) mechanism by which TREM1/3 deficiency drives senescence in TECs. This involves redox imbalance, mitochondrial dysfunction and a decline in cellular metabolic activities. These finding suggest a novel role for TREM-1 in maintaining tubular homeostasis through regulation of mitochondrial metabolic flexibility

Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans

AIMS: Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)-induced proinflammatory gene expression and cytokine production in leucocytes and on neutrophil functions. METHODS: Six healthy humans were studied on four occasions for 6 h during: (i) lower insulinaemic euglycaemic clamp, (ii) lower insulinaemic hyperglycaemic clamp, (iii) hyperinsulinaemic euglycaemic clamp, and (iv) hyperinsulinaemic hyperglycaemic clamp. Target levels of plasma glucose were 12.0 mmol/l (hyperglycaemic clamps) or 5.0 mmol/l (euglycaemic clamps). Target plasma insulin levels were 400 pmol/l (hyperinsulinaemic clamps) or 100 pmol/l (lower insulinaemic clamps). RESULTS: Hyperglycaemia reduced LPS-induced mRNA expression of nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), interleukin-1 alpha (IL1A) and chemokine (C-C motif) ligand 3 (CCL3), whereas during hyperinsulinaemia enhanced mRNA levels occurred in six out of eight measured inflammation-related genes, irrespective of plasma glucose levels. Combined hyperglycaemia and hyperinsulinaemia led to enhanced IL1A, interleukin-1 beta (IL1B) and CCL3 mRNA levels upon LPS stimulation. Neither hyperglycaemia nor hyperinsulinaemia altered cytokine protein production, neutrophil migration, phagocytic capacity or oxidative burst activity. CONCLUSIONS: These results suggest that short-term hyperglycaemia and hyperinsulinaemia influence the expression of several inflammatory genes in an opposite direction, that the acute effects of hyperinsulinaemia on inflammatory mRNA levels may be stronger than those of hyperglycaemia, and that the effects of insulin, in particular, may be relevant in the concurrent presence of hyperglycaemi

Effect of TREM-1 blockade and single nucleotide variants in experimental renal injury and kidney transplantation

Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development of delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition receptor expressed on a variety of innate immune cells. TREM-1 expression increases following acute and chronic renal injury. However, the function of TREM-1 in renal IR is still unclear. Here, we investigated expression and function of TREM-1 in a murine model of renal IR using different TREM-1 inhibitors: LP17, LR12 and TREM-1 fusion protein. In a human study, we analyzed the association of non-synonymous single nucleotide variants in the TREM1 gene in a cohort comprising 1263 matching donors and recipients with post-transplant outcomes, including DGF. Our findings demonstrated that, following murine IR, renal TREM-1 expression increased due to the influx of Trem1 mRNA expressing cells detected by in situ hybridization. However, TREM-1 interventions by means of LP17, LR12 and TREM-1 fusion protein did not ameliorate IR-induced injury. In the human renal transplant cohort, donor and recipient TREM1 gene variant p. Thr25Ser was not associated with DGF, nor with biopsy-proven rejection or death-censored graft failure. We conclude that TREM-1 does not play a major role during experimental renal IR and after kidney transplantation

Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

<p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p

Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

<p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p

Gaze fixation improves the stability of expert juggling

Novice and expert jugglers employ different visuomotor strategies: whereas novices look at the balls around their zeniths, experts tend to fixate their gaze at a central location within the pattern (so-called gaze-through). A gaze-through strategy may reflect visuomotor parsimony, i.e., the use of simpler visuomotor (oculomotor and/or attentional) strategies as afforded by superior tossing accuracy and error corrections. In addition, the more stable gaze during a gaze-through strategy may result in more accurate movement planning by providing a stable base for gaze-centered neural coding of ball motion and movement plans or for shifts in attention. To determine whether a stable gaze might indeed have such beneficial effects on juggling, we examined juggling variability during 3-ball cascade juggling with and without constrained gaze fixation (at various depths) in expert performers (n = 5). Novice jugglers were included (n = 5) for comparison, even though our predictions pertained specifically to expert juggling. We indeed observed that experts, but not novices, juggled significantly less variable when fixating, compared to unconstrained viewing. Thus, while visuomotor parsimony might still contribute to the emergence of a gaze-through strategy, this study highlights an additional role for improved movement planning. This role may be engendered by gaze-centered coding and/or attentional control mechanisms in the brain

Grasping and hitting moving objects

Some experimental evidence suggests that grasping should be regarded as independent control of the thumb and the index finger (digit control hypothesis). To investigate this further, we compared how the tips of the thumb and the index finger moved in space when grasping spheres to how they moved when they were hitting the sphere using only one digit. In order to make the tasks comparable, we designed the experiment in such a way that subjects contacted the spheres in about the same way in the hitting task as when grasping it. According to the digit control hypothesis, the two tasks should yield similar digit trajectories in space. People hit and grasped stationary and moving spheres. We compared the similarity of the digits' trajectories across the two tasks by evaluating the time courses of the paths of the average of the thumb and the index finger. These paths were more similar across tasks than across sphere motion, supporting the notion that grasping is not controlled fundamentally differently than hitting. © 2011 The Author(s)

Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

RAGE does not contribute to renal injury and damage upon ischemia/reperfusion-induced injury.

Item does not contain fulltextThe receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses in renal diseases, but its role in renal ischemia/reperfusion (I/R) injury is unknown. We showed that during renal I/R, RAGE ligands HMGB1 and S100B are expressed. However, RAGE deficiency does not affect renal injury and function upon I/R-induced injury