From forecasting to ‘la prospective’ a new way of looking at futures

Although‘La Prospective’is not well known in the Anglo-Saxon forecasting literature, it has been for many years widely used in France and other Latin countries with considerable success. Lately, because of the inaccuracy of forecasting and the large forecasting errors that have been experienced, it is suggested that the Prospective approach can be used as a way of dealing with these problems. The main characteristics of‘La Prospective’are that it does not look at the future as a continuation of the past but rather as the outcome of the wishes of various actors and the constraints imposed on them by the environment. Its purpose is to assist in creating alternative futures and then select some alternative that allows for maximum freedom of action.     

Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms

Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling. In the heart, NO inhibits L-type Ca2+ channels but stimulates sarcoplasmic reticulum (SR) Ca2+ release, leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae, where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels allows NO to inhibit beta-adrenergic-induced inotropy. Neuronal NO synthase (NOS1), however, is targeted to cardiac SR. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro, suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1-/- and NOS3-/- mice develop age-related hypertrophy, although only NOS3-/- mice are hypertensive. NOS1/3-/- double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function.     

The timing of the last deglaciation in North Atlantic climate records

To determine the mechanisms governing the last deglaciation and the sequence of events that lead to deglaciation, it is important to obtain a temporal framework that applies to both continental and marine climate records. Radiocarbon dating has been widely used to derive calendar dates for marine sediments, but it rests on the assumption that the 'apparent age' of surface water (the age of surface water relative to the atmosphere) has remained constant over time. Here we present new evidence for variation in the apparent age of surface water (or reservoir age) in the North Atlantic ocean north of 40 degrees N over the past 20,000 years. In two cores we found apparent surface-water ages to be larger than those of today by 1,230 +/- 600 and 1,940 +/- 750 years at the end of the Heinrich 1 surge event (15,000 years BP) and by 820 +/- 430 to 1,010 +/- 340 years at the end of the Younger Dryas cold episode. During the warm B?lling-Aller?d period, between these two periods of large reservoir ages, apparent surface-water ages were comparable to present values. Our results allow us to reconcile the chronologies from ice cores and the North Atlantic marine records over the entire deglaciation period. Moreover, the data imply that marine carbon dates from the North Atlantic north of 40 degrees N will need to be corrected for these highly variable effects.     

Disruption of fragmented parent bodies as the origin of asteroid families

Asteroid families are groups of small bodies that share certain orbit and spectral properties. More than 20 families have now been identified, each believed to have resulted from the collisional break-up of a large parent body in a regime where gravity controls the outcome of the collision more than the material strength of the rock. The size and velocity distributions of the family members provide important constraints for testing our understanding of the break-up process, but erosion and dynamical diffusion of the orbits over time can erase the original signature of the collision. The recently identified young Karin family provides a unique opportunity to study a collisional outcome almost unaffected by orbit evolution. Here we report numerical simulations modelling classes of collisions that reproduce the main characteristics of the Karin family. The sensitivity of the outcome of the collision to the internal structure of the parent body allows us to show that the family must have originated from the break-up of a pre-fragmented parent body, and that all large family members formed by the gravitational reaccumulation of smaller bodies. We argue that most of the identified asteroid families are likely to have had a similar history.     

Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination

Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.     

Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin

We have identified nonsense mutations in the gene CDSN (encoding corneodesmosin) in three families suffering from hypotrichosis simplex of the scalp (HSS; OMIM 146520). CDSN, a glycoprotein expressed in the epidermis and inner root sheath (IRS) of hair follicles, is a keratinocyte adhesion molecule. Truncated CDSN aggregates were detected in the superficial dermis and at the periphery of hair follicles. Our findings suggest that CDSN is important in normal scalp hair physiology.     

Mitochondrial class II introns encode proteins related to the reverse transcriptases of retroviruses

Organelle introns share several distinctive features that set them apart from their counterparts in nuclear-encoded pre-messenger RNAs (reviewed in ref. 1): their termini do not obey the GU...AG rule; the introns are 'structured' (members of the same family or 'class' can theoretically adopt very similar RNA secondary conformations and several of the postulated pairings have been confirmed by studies of splicing mutants and their revertants (see, for example, ref. 4); many introns from both classes contain long open reading frames. We report here that the proteins potentially encoded by four class II introns are related to several RNA-dependent polymerases of viral and transposable element origins.