Glycation induces formation of amyloid cross-beta structure in albumin

Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA.     

Estimating root lifespan of two grasses at contrasting elevation in a salt marsh by applying vitality staining on roots from in-growth cores

Contrasting soil conditions caused by different inundation frequenciesrequire different root growth strategies along the elevational gradient ofcoastal salt marshes. The objective of this study was to examine (1) if rootlifespan was shorter in Elymus pycnanthus, a relativelyfast-growing competitive species dominating high marshes, than inSpartina anglica, a relatively slow-growingstress-tolerating species dominating low marshes, and (2) if the species withlonger lifespan had higher tissue density (g cm^–3) and lowerspecific root length (m g^–1) than the species with shorterlifespan. Root production and mortality rates were established by samplingrootsin in-growth cores, and using triphenyltetrazolium chloride (TTC) staining todistinguish vital from dead roots. Root lifespan was estimated by dividing theliving root biomass (Elymus: 36 gm^–2, Spartina: 100 gm^–2) by root production (Elymus:0.28 g day^–1 m^–2,Spartina: 0.25 g day^–1m^–2) or root mortality rates(Elymus: 0.42–0.53 g day^–1m^–2). Spartina did not exhibitsubstantial mortality. Despite the present method only yielding rough estimatesof average root lifespan, it is evident that root longevity is much shorter inElymus than in Spartina. Rootlifespanranged between 10–19 weeks for Elymus but was closeto 1 year in Spartina, indicating thatElymus replaces it's roots continuously throughout thegrowing season, whereas Spartina maintains its roots overthe growing season. Fine roots of Elymus had slightlylowertissue density (0.094) than those of Spartina (0.139),whereas coarse roots of Elymus andSpartina had similar tissue density (0.100 gcm^–3). Fine roots of Elymus andSpartina had similar specific root length (195 mg^–1). However, coarse roots ofElymus (50 m g^–1) had higherspecific root length than those of Spartina (20 mg^–1) due to having smaller root diameter(Elymus: 548 m,Spartina: 961 m). We conclude thatpresentobservations on Elymus and Spartinasupport our first hypothesis that the competitive species fromthehigh marsh had short-lived roots compared to the'stress-tolerating'species from the low marsh. However, our result provide only weak support forthe existence of a positive correlation between root longevity and tissuedensity and a negative correlation between root longevity and specific rootlength.     

Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage

Thrombin-activable fibrinolysis inhibitor (TAFI) is present in the circulation as an inactive zymogen. Thrombin converts TAFI to a carboxypeptidase B-like enzyme (TAFIa) by cleaving at Arg(92) in a process accelerated by the cofactor, thrombomodulin. TAFIa attenuates fibrinolysis. TAFIa can be inactivated by both proteolysis by thrombin and spontaneous temperature-dependent loss of activity. The identity of the thrombin cleavage site responsible for loss of TAFIa activity was suggested to be Arg(330), but site-directed mutagenesis of this residue did not prevent inactivation of TAFIa by thrombin. In this study we followed TAFI activation and TAFIa inactivation by thrombin/thrombomodulin in time and characterized the cleavage pattern of TAFI using matrix-assisted laser desorption ionization mass spectrometry. Mass matching of the fragments revealed that TAFIa was cleaved at Arg(302). Studies of a mutant R302Q-TAFI confirmed identification of this thrombin cleavage site and, furthermore, suggested that inactivation of TAFIa is based on its conformational instability rather than proteolytic cleavage at Arg(302).     

Platypnoea-orthodeoxia syndrome,an underdiagnosed cause of hypoxaemia: four cases and the possible underlying mechanisms

Cardiac platypnoea-orthodeoxia syndrome (POS) is a position-dependent condition of dyspnoea and hypoxaemia due to right-to-left shunting. It often remains unrecognised in clinical practice, possibly because of its complex underlying pathophysiology. We present four consecutive patients with POS and patent foramen ovale (PFO) who underwent a successful percutaneous PFO closure, describe the mechanism of their POS and provide a review of the literature.     

Ecosystem Engineering by Plants on Wave-Exposed Intertidal Flats Is Governed by Relationships between Effect and Response Traits

In hydrodynamically stressful environments, some species—known as ecosystem engineers—are able to modify the environment for their own benefit. Little is known however, about the interaction between functional plant traits and ecosystem engineering. We studied the responses of Scirpus tabernaemontani and Scirpus maritimus to wave impact in full-scale flume experiments. Stem density and biomass were used to predict the ecosystem engineering effect of wave attenuation. Also the drag force on plants, their bending angle after wave impact and the stem biomechanical properties were quantified as both responses of stress experienced and effects on ecosystem engineering. We analyzed lignin, cellulose, and silica contents as traits likely effecting stress resistance (avoidance, tolerance). Stem density and biomass were strong predictors for wave attenuation, S. maritimus showing a higher effect than S. tabernaemontani. The drag force and drag force per wet frontal area both differed significantly between the species at shallow water depths (20 cm). At greater depths (35 cm), drag forces and bending angles were significantly higher for S. maritimus than for S. tabernaemontani. However, they do not differ in drag force per wet frontal area due to the larger plant surface of S. maritimus. Stem resistance to breaking and stem flexibility were significantly higher in S. tabernaemontani, having a higher cellulose concentration and a larger cross-section in its basal stem parts. S. maritimus had clearly more lignin and silica contents in the basal stem parts than S. tabernaemontani. We concluded that the effect of biomass seems more relevant for the engineering effect of emergent macrophytes with leaves than species morphology: S. tabernaemontani has avoiding traits with minor effects on wave attenuation; S. maritimus has tolerating traits with larger effects. This implies that ecosystem engineering effects are directly linked with traits affecting species stress resistance and responding to stress experienced.     

Giant pseudoaneurysm after aortic root replacement

A 22-year-old woman was born with a bicuspid aortic valve. Initially she underwent a valvulotomy, followed by a Ross procedure nine years later. Because of dilation of the autograft, a root replacement was performed with a Freestyle stentless bioprosthesis.     

Biomechanical warfare in ecology; negative interactions between species by habitat modification

Since the introduction of the term ecosystem engineering by Jones et al. many studies have focused on positive, facilitative interactions caused by ecosystem engineering. Much less emphasis has been placed on the role of ecosystem engineering in causing negative interactions between species. Here, we report on negative interactions between two well known ecosystem engineers occurring at the interface of salt marsh and intertidal flat (i.e. common cordgrass Spartina anglica and lugworms Arenicola marina ), via modification of their joint habitat. A field survey indicated that, although both species share a common habitat, they rarely co-occur on small spatial scales (<1 m). Experiments in the field and in mesocosms reveal that establishment of small Spartina plants is inhibited in Arenicola -dominated patches because of low sediment stability induced by the lugworms. In turn, Arenicola establishment in Spartina -dominated patches is limited by high silt content, compactness and dense rooting of the sediment caused by Spartina presence. Our results show that negative interactions by modification of the environment can result in rapid mutual exclusion, particularly if adverse effects of habitat modification are strong and if both species exhibit positive feedbacks. This illustrates the potential for negative interactions via the environment to affect community composition.     

Patent ductus arteriosus in adults – indications and possibilities for closure

Patent ductus arteriosus (PDA) is a rare diagnosis in adults, since symptoms and signs usually occur in infancy and most cases are treated shortly after diagnosis. We present two patients who were first diagnosed with PDA during adulthood. The first case represents a more severe form of PDA, where the need for closure of the PDA is obvious. In the second case the sequelae of the PDA are less clear. In both patients, closure of the PDA (surgically in one case, percutaneously in the other) was successful.