Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth

Angiogenesis, the formation of new capillaries, which is observed in embryonic and injured tissue and is particularly prominent in the vicinity of solid tumours, involves the migration and proliferation of capillary endothelial cells. It is probably triggered by agents, such as basic fibroblast growth factor (bFGF), thought to be released from tissues adjacent to proliferating capillaries. As well as being a potent inducer of cell division in capillary endothelial cells in vitro, bFGF can act as an angiogenic agent in vivo. It is present in a wide variety of richly vascularized tissues including brain, pituitary, retina, adrenal gland, kidney, corpus luteum, placenta and various tumours. So far, however, the normal bFGF-producing cell species in these tissues have not been identified. We report here that capillary endothelial cells express the bFGF gene, that they produce and release bFGF and that bFGF derived from them can stimulate the proliferation of capillary endothelial cells. We conclude that bFGF can act as a self-stimulating growth factor for capillary endothelial cells, and that it is possible that the formation of new capillaries is induced by capillary endothelial cells themselves.     

The transpiration of water at negative pressures in a synthetic tree

Plant scientists believe that transpiration-the motion of water from the soil, through a vascular plant, and into the air-occurs by a passive, wicking mechanism. This mechanism is described by the cohesion-tension theory: loss of water by evaporation reduces the pressure of the liquid water within the leaf relative to atmospheric pressure; this reduced pressure pulls liquid water out of the soil and up the xylem to maintain hydration. Strikingly, the absolute pressure of the water within the xylem is often negative, such that the liquid is under tension and is thermodynamically metastable with respect to the vapour phase. Qualitatively, this mechanism is the same as that which drives fluid through the synthetic wicks that are key elements in technologies for heat transfer, fuel cells and portable chemical systems. Quantitatively, the differences in pressure generated in plants to drive flow can be more than a hundredfold larger than those generated in synthetic wicks. Here we present the design and operation of a microfluidic system formed in a synthetic hydrogel. This synthetic 'tree' captures the main attributes of transpiration in plants: transduction of subsaturation in the vapour phase of water into negative pressures in the liquid phase, stabilization and flow of liquid water at large negative pressures (-1.0 MPa or lower), continuous heat transfer with the evaporation of liquid water at negative pressure, and continuous extraction of liquid water from subsaturated sources. This development opens the opportunity for technological uses of water under tension and for new experimental studies of the liquid state of water.     

Cellular maintenance of nuclear protein homeostasis

The accumulation and aggregation of misfolded proteins is the primary hallmark for more than 45 human degenerative diseases. These devastating disorders include Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis. Over 15 degenerative diseases are associated with the aggregation of misfolded proteins specifically in the nucleus of cells. However, how the cell safeguards the nucleus from misfolded proteins is not entirely clear. In this review, we discuss what is currently known about the cellular mechanisms that maintain protein homeostasis in the nucleus and protect the nucleus from misfolded protein accumulation and aggregation. In particular, we focus on the chaperones found to localize to the nucleus during stress, the ubiquitin–proteasome components enriched in the nucleus, the signaling systems that might be present in the nucleus to coordinate folding and degradation, and the sites of misfolded protein deposition associated with the nucleus.     

Institutionalizing Insider Action Research Initiatives in Organizations: The Role of Learning Mechanisms

Managers face increasing pressure to find ways to surface, utilize and integrate bits and pieces of relevant knowledge that reside within and outside the organizational boundaries to address emerging challenges. Grappling with this issue and based on a longitudinal study with a biopharma company, this paper offers the notion that insider action research coupled with the design and management of learning mechanism tapestry can enhance continuous organizational learning and improvement. The institutionalization of the learning mechanism tapestry provided new capability that enhanced the organization’s agility as well as a way to stabilize insider action research role and practices.     

Some comments on the initialization of exponential smoothing

It is shown that the traditional choice for the initial smoothed statistics in general exponential smoothing leads to the same forecasts as the equivalent ARIMA model, provided that one uses zero starting values for the initial shocks. In addition, an initialization which uses ‘backforecasts’ as initial smoothed statistics is considered, and its relationship to unconditional least squares is explored.     

EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF

Cross-communication between different signalling systems allows the integration of the great diversity of stimuli that a cell receives under varying physiological situations. The transactivation of epidermal growth factor receptor (EGFR)-dependent signalling pathways upon stimulation of G-protein-coupled receptors (GPCRs), which are critical for the mitogenic activity of ligands such as lysophosphatidic acid, endothelin, thrombin, bombesin and carbachol, provides evidence for such an interconnected communication network. Here we show that EGFR transactivation upon GPCR stimulation involves proHB-EGF and a metalloproteinase activity that is rapidly induced upon GPCR-ligand interaction. We show that inhibition of proHB-EGF processing blocks GPCR-induced EGFR transactivation and downstream signals. The pathophysiological significance of this mechanism is demonstrated by inhibition of constitutive EGFR activity upon treatment of PC3 prostate carcinoma cells with the metalloproteinase inhibitor batimastat. Together, our results establish a new mechanistic concept for cross-communication among different signalling systems.     

Length of the year in pre-epicyclic planetary theory

An estimate is made of the length of the year implied in the pre-epicyclic planetary theory of the Pañcasiddhntik. It is shown that this could be the same as the year-length of the corresponding Babylonian theory.