Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control.

The Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21(WAF1/Cip1) gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-Jkappa protein to the p21 promoter. We show here that Notch 1 activation functions also through a second Calcineurin-dependent mechanism acting on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene, Calcineurin contributes significantly to the transcriptional response of keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype, associated with altered expression of Notch-responsive genes involved in hair follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth/differentiation control.

Growth and demise of Permian biogenic chert along northwest Pangea: evidence for end-Permian collapse of thermohaline circulation

The Permian Chert Event (PCE) was a 30 Ma long episode of unusual chert accumulation along the northwest margin of Pangea, and possibly worldwide. The onset of the PCE occurred at about the Sakmarian-Artinskian boundary in the Sverdrup Basin, Canadian Arctic, where it coincides with a maximum flooding event, the ending of high-frequency/high-amplitude shelf cyclicity, the onset of massive biogenic chert deposition in deep-water distal areas, and a long-term shift from warm- to cool-water carbonate sedimentation in shallow-water proximal areas. A similar and coeval shift is observed from the Barents Sea to the northwestern USA. A landward and southward expansion of silica factories occurred during the Middle and Late Permian at which time warm-water carbonate producers disappeared completely from the northwest margin of Pangea. Biotically impoverished and increasingly narrow cold-water carbonate factories (characterised by non-cemented bioclasts of sponges, bryozoans, echinoderms and brachiopods) were then progressively replaced by silica factories. By Late Permian time, little carbonate sediments accumulated in the Barents Sea and in the Sverdrup Basin. where the deep- to shallow-water sedimentary spectrum was occupied by siliceous sponge spicules. By that time, biogenic silica sedimentation was common throughout the world. Silica factories collapsed in the Late Permian, abruptly bringing the PCE to an end. In northwest Pangea, the end- Permian collapse of the PCE was associated with a major transgression and with a return to much warmer oceanic and continental climatic conditions. Chert deposition resumed in the distal oceanic areas during the early Middle Triassic (Anisian) after a 8-10 Ma interruption (Early Triassic Chert Gap). The conditions necessary for the onset, expansion and zenith of the PCE were provided by the thermohaline circulation of nutrient-rich cold waters along the northwestern and western margin of Pangea, and possibly throughout the world oceans. These conditions provided an efficient transportation mechanism that constantly replenished the supply of silica in the area, created a nutrient- and oxygen-rich environment favouring siliceous biogenic productivity. established cold sea-floor conditions, hindering silica dissolution, while increasing calcium carbonate solubility, and provided conditions adverse to organic and inorganic carbonate production, The northwest margin of Pangea was, for nearly 30 Ma. bathed by cold waters presumably derived from the seasonal melting of northern sea ice, the assumed engine for thermohaline circulation. This process started near the Sakmarian-Artinskian boundary. intensified throughout Middle and Late Permian time and ceased suddenly in latest Permian time, It led to oceanic conditions much colder than normally expected from the palaeolatitudes. and the influence of cold northerly-derived water was felt as far south southern Nevada. The demise of silica factories was caused by the rapid breakdown of these conditions and the establishment of a much warmer marine environment accompanied by sluggish circulation and perhaps a reduced input of dissolved silica to the ocean. Complete thawing of northern sea ice would have ended thermohaline circulation and led to warm and sluggish oceanic conditions inimical to the production. accumulation and preservation of biogenic silica.

Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents.

Dual-energy X-ray absorptiometry (DXA) is the most widely used technical instrument for evaluating bone mineral content (BMC) and density (BMD) in patients of all ages. However, its use in pediatric patients, during growth and development, poses a much more complex problem in terms of both the technical aspects and the interpretation of the results. For the adults population, there is a well-defined term of reference: the peak value of BMD attained by young healthy subjects at the end of skeletal growth. During childhood and adolescence, the comparison can be made only with healthy subjects of the same age, sex and ethnicity, but the situation is compounded by the wide individual variation in the process of skeletal growth (pubertal development, hormone action, body size and bone size). The International Society for Clinical Densitometry (ISCD) organized a Pediatric Position Development Conference to discuss the specific problems of bone densitometry in growing subjects (9-19 years of age) and to provide essential recommendations for its clinical use.

Research and development, where people are exposed to nanomaterials

OBJECTIVES: Many nanomaterials (materials with structures smaller than 100 nm) have chemical, physical and bioactive characteristics of interest for novel applications. Considerable research efforts have been launched in this field. This study aimed to study exposure scenarios commonly encountered in research settings. METHODS: We studied one of the leading Swiss universities and first identified all research units dealing with nanomaterials. After a preliminary evaluation of quantities and process types used, a detailed analysis was conducted in units where more than a few micrograms were used per week. RESULTS: In the investigated laboratories, background levels were usually low and in the range of a few thousand particles per cubic centimeter. Powder applications resulted in concentrations of 10,000 to 100,000 particles/cm(3) when measured inside fume hoods, but there were no or mostly minimal increases in the breathing zone of researchers. Mostly low exposures were observed for activities involving liquid applications. However, centrifugation and lyophilization of nanoparticle-containing solutions resulted in high particle number levels (up to 300,000 particles/cm(3)) in work spaces where researchers did not always wear respiratory protection. No significant increases were found for processes involving nanoparticles bound to surfaces, nor were they found in laboratories that were visualizing properties and structure of small amounts of nanomaterials. CONCLUSIONS: Research activities in modern laboratories equipped with control techniques were associated with minimal releases of nanomaterials into the working space. However, the focus should not only be on processes involving nanopowders but should also be on processes involving nanoparticle-containing liquids, especially if the work involves physical agitation, aerosolization or drying of the liquids.

Plant Phototropic Growth.

Plants are photoautotrophic sessile organisms that use environmental cues to optimize multiple facets of growth and development. A classic example is phototropism - in shoots this is typically positive, leading to growth towards the light, while roots frequently show negative phototropism triggering growth away from the light. Shoot phototropism optimizes light capture of leaves in low light environments and hence increases photosynthetic productivity. Phototropins are plasma-membrane-associated UV-A/blue-light activated kinases that trigger phototropic growth. Light perception liberates their protein kinase domain from the inhibitory action of the amino-terminal photosensory portion of the photoreceptor. Following a series of still poorly understood events, phototropin activation leads to the formation of a gradient of the growth hormone auxin across the photo-stimulated stem. The greater auxin concentration on the shaded compared with the lit side of the stem enables growth reorientation towards the light. In this Minireview, we briefly summarize the signaling steps starting from photoreceptor activation until the establishment of a lateral auxin gradient, ultimately leading to phototropic growth in shoots.

Sensing the light environment in plants: photoreceptors and early signaling steps.

Plants must constantly adapt to a changing light environment in order to optimize energy conversion through the process of photosynthesis and to limit photodamage. In addition, plants use light cues for timing of key developmental transitions such as initiation of reproduction (transition to flowering). Plants are equipped with a battery of photoreceptors enabling them to sense a very broad light spectrum spanning from UV-B to far-red wavelength (280-750nm). In this review we briefly describe the different families of plant photosensory receptors and the mechanisms by which they transduce environmental information to influence numerous aspects of plant growth and development throughout their life cycle.